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* The Multiple Risk Factor Intervention Trial was a randomized primary prevention trial to test the effect of a multifactor intervention program on mortality from coronary heart disease (CHD) in 12,866 high-risk men aged 35 to 57 years. Men were randomly assigned either to a special intervention (SI) program consisting of stepped-care treatment for hypertension, counseling for cigarette smoking, and dietary advice for lowering blood cholesterol levels, or to their usual sources of health care in the community (UC). Over an average follow-up period of seven years, risk factor levels declined in both groups but to a greater degree for the SI men. Mortality from CHD was 17.9 deaths per 1,000 in the SI group and 19.3 per 1,000 in the UC group, a statistically nonsignificant difference of 7.1% (90% confidence interval, -15% to 25%). Total mortality rates were 41.2 per 1,000 (SI) and 40.4 per 1,000 (UC). Three possible explanations for these findings are considered: (1) the overall intervention program, under these circumstances, does not affect CHD mortality; (2) the intervention used does affect CHD mortality, but the benefit was not observed in this trial of seven years' average duration, with lower-than-expected mortality and with considerable risk factor change in the UC group; and (3) measures to reduce cigarette smoking and to lower blood cholesterol levels may have reduced CHD mortality within subgroups of the SI cohort, with a possibly unfavorable response to antihypertensive drug therapy in certain but not all hypertensive subjects. This last possibility was considered most likely, needs further investigation, and lends support to some preventive measures while requiring reassessment of others.
September 24, 1982
THE YEARS subsequent to World War II saw increasing evidence of the importance of arteriosclerosis and its complications as the leading cause of death in the United States. Scientific studies in the laboratory, clinic, and in population groups pointed to the contributing roles of diet, hypertension, cigarette smoking, diabetes, and other risk factors in the genesis of coronary heart disease (CHD). Yet convincing demonstrations of the favorable effect of risk factor modification on CHD morbidity and mortality were not at hand by the 1960s.
In July 1970, the National Heart and Lung Institute (NHLI) convened a Task Force on Arteriosclerosis specifically to develop a broad long-range plan for the study, control, and possible prevention of arteriosclerosis. [1] The Task Force concluded that the time had come for vigorous application of existing knowledge for the purpose of determining whether CHD could be prevented. Among its final recommendations were (1) the advice not to institute a large-scale national diet-heart trial because of excessive cost and uncertain feasibility, and (2) a proposal that multiple risk factor intervention trials be undertaken to ascertain whether modification of elevated serum cholesterol levels, hypertension, and cigarette smoking in persons at increased risk of death from heart attacks would result in reduction of coronary death rates. With acceptance of the latter proposal, the NHLI prepared and distributed requests for participation of clinical and support centers in the Multiple Risk Factor Intervention Trial (MRFIT).
In 1972 and 1973, awards from the NHLI (later the National Heart, Lung, and Blood Institute, or NHLBI) were made to 22 clinical centers, a coordinating center, a laboratory center, a laboratory standardization center, and two electrocardiography centers. A policy advisory board, whose members had no formal association with any of the other participating units of the trial, was appointed by the Institute to provide advice on the overall course of the trial and to monitor the effects of intervention. [2] A steering committee comprised of investigators from the clinical and support centers and NHLBI staff was responsible for the scientific leadership of the trial. [3]
The MRFIT design called for the recruitment of at least 12,000 men aged 35 to 57 years who were at increased risk of death from CHD, but had no clinical evidence of CHD. Persons were designated at "increased risk" if their levels of three risk factors-cigarette smoking, serum cholesterol, and blood pressure (BP)-were sufficiently high at a first screening visit to place them in the upper 15% of a risk score distribution based on data from the Framingham Heart Study. [4] After about one third of the screening was completed and success in recruitment had been demonstrated, the 15% was changed to 10% to increase the average risk level of the eligible men. As an example of the application of this criterion, a man whose diastolic BP was 90 mm Hg and who reported smoking 30 cigarettes per day was risk-eligible at the 10% level if his serum cholesterol level was at least 295 mg/dL. The study was restricted to men because of their much higher risk of premature heart attack compared with women.
The men were to be randomized into two groups of approximately equal size. One group received a "special intervention" (SI) program aimed at cessation of cigarette smoking and reduction of elevated serum cholesterol and BP levels. Men in the other group, "usual care" (UC), were referred to their personal physicians or other community medical facility for such treatment of their risk factors as was considered individually appropriate.
As a first step in identifying at least 12,000 men eligible for the trial, 361,662 men were recruited for a first screening visit to determine CHD risk eligibility and to apply several exclusion criteria. Various recruitment techniques were used, with the most common procedure being to offer voluntary screening to industry or government employee groups. The number recruited for screening at each center ranged from 11,435 to 30,465. The men were informed at the first as well as at subsequent screening visits of the randomized nature of the trial.
Eligibility Criteria
Eligibility was determined at three successive screening visits (S (1), S2, and S3). At S1, to determine risk for CHD, systolic and diastolic BPs were measured, the number of cigarettes smoked daily was ascertained, and a sample of blood was drawn for determination of the serum cholesterol level. Men were excluded from further screening on the basis of low risk, history of a heart attack, diabetes mellitus requiring medication, expected geographic mobility, a serum cholesterol level of 350 mg/dL or higher, or diastolic BP of 115 mm Hg or higher. The last two exclusions were made because of their special clinical features and therapeutic requirements. Of the men seen at S1, 25,545 (7.1%) qualified and were invited to return for S (2).
The second screening visit, S2, followed a 12-hour fast and included among other tests (1) a medical history and physical examination; (2) four BP determinations; (3) a locally read resting ECG; (4) a fasting blood sample for measurement of cholesterol, triglyceride, lipoprotein cholesterol, serum thiocyanate, and potassium levels, as well as a blood sample drawn one hour after a 75-g glucose load; (5) pulmonary function tests; (6) a posterior-anterior chest film; (7) an assessment of willingness and ability to adhere to the proposed intervention program; and (8) a detailed explanation of the purposes of the trial and requirements for participation.
Reasons for excluding men at this visit included body weight greater than or equal to 150% of desirable weight; angina pectoris as determined by the Rose questionnaire [5]; history or ECG evidence of myocardial infarction; untreated symptomatic diabetes; diets incompatible with the MRFIT food pattern; treatment with guanethidine, hydralazine, insulin, oral hypoglycemic agents, or lipid-lowering agents; illnesses or disabilities likely to impair full participation in the trial; and diastolic BP of 120 mm Hg or higher. Of the 22,080 men seen at the S2 visit, 15,791 men (71.5%) were invited to return for the third and final screening visit.
The third screening visit, S3, included (1) a resting and exercise ECG, (2) a detailed smoking questionnaire, and (3) a 24-hour dietary recall. A brief medical review and examination determined whether any major change in cardiovascular status had occurred since S2. The purpose and scope of the trial were again explained, and men who then signed the consent form were randomized by the coordinating center into either the SI or UC group. The randomization assignment was obtained by the local clinic coordinator who telephoned the coordinating center after eligibility and willingness to enter the trial had been established. Allocation to SI or UC was stratified by clinic and balanced in blocks of four or six, providing two groups of nearly equal size at each clinic, with 6,428 assigned studywide to SI and 6,438 to UC. Of the 14,111 men seen at S3, 12,866 were randomized into the trial, constituting a yield of 3.6% of men seen at S1. The first man was randomized in December 1973; the last randomization occurred on Feb 28, 1976.
Intervention Program
No intervention program was offered to the UC men who continued to be followed by their usual source of medical care, but they were invited to return once a year for a medical history, physical examination, and laboratory studies as listed herein. The results of the screening and annual examinations were provided to their personal physicians, who were informed as to the scientific objectives of the study.
The detailed components of the SI program have been reported earlier [6-9] and are summarized here. The initial phase of intervention was an intensive integrated effort to lower the three major risk factors. Immediately after randomization to the SI group, each cigarette smoker was counseled individually by a study physician in an effort to achieve cessation of smoking at that time. Shortly thereafter, each SI man was invited with his spouse or friend to a series of weekly group discussions addressing all three risk factors; uniformity of structure and content was sought by the use of common protocols and educational materials. Each group included about ten men and met for about ten sessions.
After the initial intensive intervention phase, individual counseling, planned and executed by an intervention team usually headed by a behavioral scientist and including nutritionists, nurses, physicians, and general health counselors, became the general approach in all three modalities. Participants in the SI group were seen every four months, and more often as needed for intervention purposes. The course of every SI participant was monitored to assess changes in risk factor status, the ultimate objective being to reach specific goals established for each individual.
Hypertension was considered present if the man reported having antihypertensive medication prescribed for him by his personal physician (regardless of BP level), or if an untreated man was found to have a diastolic BP of at least 90 mm Hg on two consecutive monthly visits during the trial. The reading at the second of these visits was used to establish a goal BP of either a 10 mm Hg reduction or 89 mm Hg, whichever was lower; men who had a diastolic BP of 90 mm Hg or less who were already taking antihypertensive drugs prescribed by a personal physician were assigned a goal of 80 mm Hg. Before drug prescription, weight reduction was attempted for overweight men. Drugs were prescribed according to a stepped-care protocol beginning with the use of either hydrochlorothiazide or chlorthalidone. Reserpine, hydralazine, guanethidine, or certain alternate drugs were sequentially added if goal BP had not been achieved. [9] The protocol also included a provision for mild sodium restriction. Participants in the SI group who had been treated with BP medication by nonstudy physicians were usually transferred, with the permission of their private physicians, to the care of an MRFIT clinician.
The nutrition intervention program sought to encourage the development of lifelong shopping, cooking, and eating patterns rather than to specify a structured diet. [7] Individual intervention goals for lowering serum cholesterol levels by an amount dependent on the entry level were established. Initially, eating patterns were recommended that reduced saturated fat intake to less than 10% of calories and dietary cholesterol intake to less than 300 mg/day, and increased polyunsaturated fat intake to 10% of calories. In 1976, the nutrition pattern was changed to specify that saturated fat be less than 8% of calories and dietary cholesterol less than 250 mg/day. Weight reduction was sought for men whose weight was 115% or greater of desirable weight by recommending reductions in caloric intake and increases in moderate forms of physical activity.
The smoking intervention program urged those SI participants who smoked cigarettes to quit; no systematic effort was made to alter the smoking habits of persons who smoked only pipes and cigars. [8] Dosage reduction, including switching to cigarettes low in tar and nicotine, was recommended only as an intermediate step to cessation. Conventional behavioral modification techniques were used throughout the trial; aversive techniques and hypnosis were used in selected instances during the final years. Particularly successful intervention approaches were the ten-week group sessions at the beginning of the trial and the five-day quit clinics during the final years.
Data Collection Methods
On or about each anniversary of randomization, participants in both the SI and UC groups returned for assessment of risk factor levels and morbidity status. Data collected at these annual visits, at screening, intervention, and four-month visits were sent to the coordinating center for processing and analysis. Serum cholesterol concentration obtained at S1, the first screening visit, for risk eligibility purposes was determined at one of 14 local laboratories established for this purpose and monitored by the Centers for Disease Control (CDC) Lipid Standardization Laboratory and the coordinating center. All subsequent analyses of blood samples for levels of cholesterol, triglycerides, lipoproteins, creatinine, potassium, glucose, uric acid, SGOT, and thiocyanate were determined by the central laboratory using techniques previously described. [10,11]
Except for the ECG taken at S2 and read locally for exclusion purposes, cassette tapes of all ECGs were sent to the ECG Center in Halifax, Nova Scotia, for computer processing and interpretation. A paper tracing produced from the cassette was then forwarded to the ECG Reading Center in Minneapolis for visual classification according to the Minnesota code. Major ECG abnormalities included major Q wave findings, ST segment elevations and depressions, negative T waves, frequent ventricular premature beats (VPBs) (>or= to 10% of recorded beats), complete atrioventricular (AV) and bundle-branch block, and supraventricular tachycardia. Minor ECG abnormalities included high R waves, left axis deviation, and less frequent VPBs (<10% of recorded beats). The treadmill exercise test at S3 was done according to a modified Bruce protocol. [12]
Cigarette smoking was measured in two ways: (1) a participant interview for smoking behavior; and (2) thiocyanate-adjusted smoking and quit rates using serum thiocyanate level as an objective measure of smoking behavior. [13]
For analyses in this report, baseline BP is defined as the average of the two random-zero manometer readings at S2 and S3; BP at each follow-up visit is the average of the two random-zero readings at the visit. A participant was considered hypertensive at entry if his baseline diastolic BP was 90 mm Hg or higher or if he reported at S2 having antihypertensive drugs prescribed for him. No attempt was made before randomization to alter antihypertensive medication for those already receiving such agents.
Serum cholesterol concentration was determined at S1 and each annual follow-up visit using automated methods with periodic quality control developed by the CDC Lipid Standardization Laboratory. [11] Plasma cholesterol and triglyceride concentrations were obtained at S2 and each annual visit except at 12 months. The cholesterol content of each lipoprotein fraction, estimated after heparin/manganese precipitation, was obtained at S (2) and at 24, 48, and 72 months. [11] All lipid determinations were performed on serum or plasma specimens collected after an overnight fast except for the serum cholesterol at the first screening visit.
Twenty-four hour dietary recalls were obtained at S3 and at 12, 24, 36, 60 (SI men only), and 72-month visits through interview by an MRFIT nutritionist. Recalls were coded by a Nutrition Coding Center (NCC) with nutrient calculations made using version VI of the NCC food table. [14]
Sample Size and Statistical Power
In planning for the MRFIT, four key endpoints were identified: (1) death from CHD (the primary endpoint); (2) death from cardiovascular disease (CVD); (3) death from any cause; and (4) the combination of fatal CHD and nonfatal myocardial infarction. Data on the first three endpoints are presented in this report on mortality; morbidity data will be included in a subsequent report. Application of the logistic function with coefficients estimated from Framingham data to the observed risk factor combinations of the men randomized projected a six-year CHD death rate for UC men of 29.0 deaths per thousand men. With a sample size of 12,866 (the number eventually randomized into the trial), a reduction in CHD mortality among 81 men to 21.3 per thousand (26.6% reduction) could be detected with a probability of.88 using a one-sided test for a difference in proportions at a.05 level of significance. This reduction was determined by using the following anticipated intervention effects (and corresponding potential risk reductions): (1) a 10% reduction of serum cholesterol level if 220 mg/dL or higher-otherwise no change; (2) a 10% reduction of diastolic BP if 95 mm Hg or higher-otherwise no change; and (3) graded reductions in cigarette smoking as follows: 25% reduction for smokers of 40 or more cigarettes per day, 40% for smokers of 20 to 39 per day, and 55% for smokers of less than 20 per day. These anticipated differential intervention effects were based on experience in earlier smoking cessation programs. [13]
In addition, it was assumed that the corresponding groups of UC smokers at entry would have reductions during the course of the trial of 5%, 10%, and 15%, respectively, but that there would be no change in serum cholesterol or BP level in the UC group. Further allowances were incorporated for nonadherence by SI men (estimated to increase progressively to 50% by the end of six years), and for time to achieve maximum potential benefit of risk factor change (estimated to be a "lag" of three years). A similar calculation for the endpoint of death from any cause gave an estimate of power of.92. Statistical aspects of the design have been reported elsewhere. [3,4]
During the trial, subgroup hypotheses relative to mortality outcome were formulated by MRFIT investigators blinded to interim mortality data with the realization that power would be lower for their testing than for comparisons based on all SI and UC men. These hypotheses were based on the recognition that, in such a group of men at increased risk of coronary disease, a proportion would have advanced coronary atherosclerosis at entry even after excluding those with clinical evidence of CHD (history of myocardial infarction or angina, or ECG evidence of myocardial infarction). One of these hypotheses, that the intervention program would be especially effective in lowering CHD mortality for men with normal baseline resting ECGs, is referred to in this article.
Mortality Ascertainment
All participants were followed for a minimum of six years, with an average period of observation of seven years. Deaths were ascertained by clinic staff through contact with family or friends of the deceased, routine follow-up of missed clinic visits, response to postcards requesting change-of-address information sent twice yearly to UC participants, and searches of publicly accessible files of deceased persons.
To determine survival status as of Feb 28, 1982 (six years after the last day of randomization), a telephone or mail contact was attempted with each man not previously known to be deceased. The status of men not located by this procedure was sought using the files of the Social Security Administration and the service of a commercial firm specializing in methods of follow-up. The 15 SI and 15 UC men whose survival status remained unknown as of July 1, 1982, are included in the analyses as survivors to Feb 28, 1982.
Cause of death was assigned by a Mortality Review Committee, a three-member panel of cardiologists not associated with any MRFIT center and not privy to interim trial results. This committee, without knowledge of study group membership of the deceased, reviewed clinic records, hospital records, next-of-kin interviews, death certificates, and reports of autopsies performed (31% of SI decedents, 33% of UC). Deaths ascribed to CHD were subclassified as (1) myocardial infarction (documented by clinical or autopsy evidence),with death occurring within 30 days of onset of symptoms or during hospitalization for acute myocardial infarction; (2) sudden death (within 24 hours of symptom onset and without documented myocardial infarction;(3) congestive heart failure due to CHD; or (4) death during hospitalization for surgery for CHD or from complications of such an operation.
Statistical Methods
Differences in baseline characteristics and in risk factor levels at annual follow-up visits between men randomly allocatedto the SI and UC groups were tested for statistical significance using Student's t (two-sided) or the 2x2 chi squared test without adjustment for multiple comparisons.
Risk factor changes over time are pre-sented as mean values for all participants who attended each visit. (Results based oncohort analysis and data imputation pro-cedures for missing values, such as substitution of either baseline or previous annual visit risk factor levels, did not differ from these in any substantial way.) Mortality results are presented as lifetable functions using the Kaplan-Meier product limit method *RF 15, 16* and as the proportion of deaths as of Feb 28, 1982, among SI and UC participants. Significance testing of mortality results is limited to the key endpoints for the entire cohort. For the three key mortality endpoints, differences between all SI and UC participants are summarized using the log rank test. [17] For the primary endpoint of CHD death, a 90% confidence interval (CI) for the percentage difference, [18] ([UC-SI]/UC)x100, between all SI and all UC men in the proportion of deaths at the end of follow-up is given since the design of the trial was based on a one-sided test at the.05 probability level. For other comparisons, the more conventional 95% CI for the percentage difference is given.
The analysis of subgroups of men is, unless otherwise noted, restricted to groups defined by baseline characteristics. Men are classified, regardless of degree of adherence, as SI or UC based on the allocation at randomization.
Comparison of SI and UC Groups at Entry
The effectiveness of the randomization process in establishing two comparable groups at baseline is demonstrated by the excellent agreement in prerandomization levels of numerous risk factor and risk factor-related variables ( Table 1). None of these differences is statistically significant at the.05 level.
Risk Factor Reduction
A necessary intermediate goal of the trial was to obtain adequate reductions, through intervention, of the three major modifiable CHD risk factors ( Figure 1). For each of these, highly statistically significant (P<.01) differences between the SI and UC groups were observed at each annual visit.
Mean plasma cholesterol level at S2 (relatively free of regression to the mean because, unlike the cholesterol level at S1, it was not used as an eligibility criterion to select men at high risk) was 240 mg/dL. After two years there were reductions of 10.4 mg/dL for SI men and 3.4 mg/dL for UC men; after six years the mean levels were 12.1 mg/dL and 7.5 mg/dL below baseline for SI and UC men, respectively. These reductions, which primarily represent changes in low-density lipoprotein (LDL)-cholesterol and not high-density lipoprotein (HDL)-cholesterol ( Table 2), amount to an SI-UC difference in total cholesterol of 4.6 mg/dL, or 2%. With the less-than-anticipated reduction among SI men and the unexpected decline among UC men, the SI-UC difference was about 50% of goal. Differences among the 22 centers in mean plasma cholesterol levels varied from -1.6 to 10.4 mg/dL at 72 months.
Several approaches were used to estimate the combined risk factor reductions. Incorporating the observed changes for the three risk factors into an expression for the relative odds (SI/UC) of CHD death using a Framingham risk function yielded an estimated relative odds 30% short of goal at 12 months, 10% short at 48 months, and nominally at goal at 72 months. This convergence to design goal largely reflects the design prediction of larger initial differentials followed by increasingly poor adherence, whereas the data show long-term maintenance of more modest initial differences. An analysis based on averaging calculated CHD risks for each participant over the six years of follow-up, indicated a potential net CHD mortality lowering of 22.2% rather than the 26.6% considered possible at the design stage; thus, this computation implies achievement of 83% of the SI-UC risk factor difference initially assumed in the design.
Mortality, All SI and UC Participants
As of Feb 28, 1982, after an average period of follow-up of seven years, there were 260 deaths among UC men, of which 124 were ascribed to CHD and 145 to cardiovascular causes (including CHD). Of 265 SI deaths, 115 were ascribed to CHD and 138 to CVD ( Table 3) and ( Table 4). The key mortality endpoints of CHD and CVD were 7.1% and 4.7% less, respectively, in the SI compared with the UC group, while the death rate for all causes was 2.1% higher for the SI men. The corresponding life table (log rank) Z values for the endpoints are +0.6, +0.4, and -0.2. None of these is statistically significant. A slight mortality advantage of the SI group, as shown by the separation of the cumulative mortality curves beginning at about two years, waned by year 5 ( Figure 2). Of the 22 clinical centers, 11 had more CHD deaths among UC men than among SI; for total mortality, ten centers had more UC than SI deaths.
The number of deaths in the UC group was substantially short of expectation for the six complete years of follow-up as well as for the average follow-up period of seven years. Based on design risk factor change assumptions and Framingham risk functions, 442 deaths (including 187 from CHD) were expected by the end of six years of follow-up among the 6,438 UC men; only 219 (including 104 from CHD) occurred. By the end of follow-up for all men, the total of 260 UC deaths (including 124 from CHD) was still well below the number expected for the six-year follow-up period. The approximate 90% CI for the percentage change in CHD mortality attributable to MRFIT intervention is therefore large, ranging from a 25% decrease to a 15% increase.
Mortality in Baseline-Defined Subgroups
Comparisons of mortality rates for SI and UC men within subgroups defined by prerandomization characteristics preserve the comparability provided by the randomization but have less precision as a result of the reduced sizes of the groups. There is also the increased likelihood of overinterpreting nominally significant differences resulting from the examination of multiple comparisons, some of which were defined post hoc. However, the subgroup findings need exploration, especially to provide insight into the overall result and to indicate areas for further investigation.
The relationship of mortality to baseline levels of the three risk factors is shown in ( Table 5), where numbers of deaths by cause together with corresponding mortality rates are given for SI and UC men. The mortality rates for smokers, for hypercholesterolemic (>or= to 250 mg/dL) and for hypertensive men are given as subtotals in the lower rows. For each of these three groups, the mortality rates are similar for SI and UC men. However, it must be remembered that subgroups defined by the presence or absence of one of the three major risk factors are not otherwise comparable; for example, because of the selection procedure used, nonsmokers have on the average higher blood cholesterol and BP levels than smokers. Despite this complexity, it may be noted in the subtotals that CHD mortality, and in most cases total mortality, tends to be higher in smokers, in participants with hypercholesterolemia, and in those with hypertension, supporting the risk factor status of these variables within this cohort.
Of the four substrata of hypertensive men, only in the smallest, con-sisting of nonsmokers who were not hypercholesterolemic, was the CHD rate lower for SI men. With only one of the three risk factors present, this group, to meet the MRFIT risk-eligibility criteria, was necessarily made up of men with more severe degrees of hypertension.
A more detailed breakdown by hypertensive status at entry is given in ( Table 6). Among hypertensive men not receiving treatment at entry, the differences in SI and UC CHD and total mortality rates differ by level of baseline diastolic BP. The percentage differences in CHD mortality rates are -45% (17 SI CHD deaths v 12 UC), -2% (19 SI CHD deaths v 19 UC), and +30% (16 SI CHD deaths v 22 UC), respectively, for participants with baseline diastolic BP levels of 90 to 94, 95 to 99, and 100 mm Hg or higher. The corresponding differences for total mortality are -55% (47 SI deaths v 31 UC), -12% (43 SI deaths v 39 UC), and +47% (25 SI deaths v 45 UC).
Intervention accomplishments in the SI group, which have been reported in detail, [6-9] were substantial: smoking cessation was much more successful than had been expected, the BP reduction in the SI group exceeded the desired drop in diastolic BP, and the effect on cholesterol lowering was considerable but less than had been sought. A notable achievement of the intervention program was a continued decline in mean risk factor levels after the substantial drop in the first year.
Risk factor changes were also observed in the UC group, though to a lesser degree. Whereas it had been projected on the basis of the best information available ten years ago that this group would exhibit over six years no important changes in BP and serum cholesterol levels, and only minimal change in smoking habits, the actual findings were very different. Sizable reductions occurred in the levels of all three risk factors for UC men. Thus, over six years, reported cigarette smoking declined from 59% to 46%, the diastolic BP from a baseline value of 90.9 to 83.6 mm Hg, and plasma cholesterol levels from 241 to 233 mg/dL. Also, 47% of the UC men were receiving antihypertensive medication at the end of the sixth year compared with 19% at baseline.
The cause of these unanticipated changes in the UC group is speculative. Contributing elements to the risk factor reductions may include the psychological impact on the UC men of enrollment in a trial limited to persons at high risk of heart attacks, the possibility that persons volunteering for a six-year trial are unusually health conscious and motivated to change, sensitization of the UC men to their risk factor status resulting from annual visits to the clinical centers, and the broad influence of health education in the United States aimed at modifying all of the three risk factors. The physicians of the UC men may well have instituted their own preventive programs. Ethical considerations prompted notification of these physicians of the findings from each annual visit, although the MRFIT centers made no recommendation regarding intervention for UC men.
The risk factor changes in the UC group may be relevant to one of the assumptions on which the power of the trial was based and that has been shown to be inaccurate. The number of deaths in the UC group was substantially short of expectation. By the end of follow-up (an average of 7.0 years) for all men, the total of 260 UC deaths (including 124 from CHD) was still slightly less than two thirds the number expected for the six-year follow-up period.
Several factors may have contributed to the lower-than-expected UC mortality: (1) the recent reduction in CHD mortality in the United States, the reasons for which are still not totally understood [19]; (2) exclusion criteria applied to the MRFIT screened group that may have been more stringent than those applied to data from the Framingham cohort during the design phase of MRFIT, resulting in the selection of men with a lower than expected mortality in both the SI and UC groups; (3) the phenomenon of lower-than-expected mortality in almost all clinical trials involving human volunteers; and (4) finally, the substantial risk factor changes made by UC men, as mentioned previously. The latter possibility can be entertained only if one assumes that risk-factor modification is effective in reducing mortality in high-risk men aged 35 to 57 years, the question the trial was designed to test.
The lower-than-predicted mortality for the UC group has the important effect of lowering the power from.88 to.75 for detecting the 26.6% SI-UC difference in mortality specified in the design. Furthermore, if the risk model based on Framingham data were accurate in predicting potential risk reduction, the unexpected decreases in UC risk-factor levels would also affect the power unfavorably. The power, based on the observed UC mortality rate, for detecting the 22% difference in CHD mortality predicted by the risk factor difference actually achieved, is about 0.6.
Interpretation of Mortality Results
The finding of percentage differences of only +7%, +5%, and -2% for CHD, CVD, and all-cause mortality rates, respectively, deserves careful examination. At least three possible explanations for these results must be considered: (1) such an intervention program is without benefit in terms of substantial decreases in mortality; (2) the intervention program does affect CHD mortality, but the benefit was not observed in this study; or (3) one or more constituents in the intervention program may have had an unfavorable effect on survival in some subgroups offsetting beneficial effects of others.
The first possibility, of ineffectiveness on CHD, CVD, and total mortality of programs to reduce cigarette smoking, treat hypertension with drugs, and lower elevated serum cholesterol levels by diet, seems inconsistent with most published scientific data: clinical, pathological, animal experimental, and epidemiologic. [19] The trial was of course initiated to test this question in high-risk middle-aged men. Only one controlled trial limited solely to testing the benefit of reduction in or cessation of cigarette smoking has been executed; its results were inconclusive, but showed a favorable trend for CHD mortality. [20] A large body of scientific data supports the conclusion that cigarette smokers who reduce the amount of smoking or give it up entirely have improved life expectancy. [21] It is not clear, however, how long it takes after modification of smoking-especially heavy smoking-for favorable alterations of mortality rates to occur, and it may take longer than the sevenyear duration of this trial to be clearly demonstrated. [22] Somewhat contrary to the possibility of a delayed effect is the observation that CHD mortality within the SI group subsequent to the first year of follow-up diverges sharply depending on smoking status at the 12-month visit. The rate in quitters who had smoked at least 30 cigarettes per day is approximately half that of those who continue smoking. Such within-group analyses, however, do not make use of the randomized control design of a clinical trial, and the results, while suggestive, leave open the possibility of confounding by other factors.
Regarding hypertension, a beneficial impact of drug treatment by a "stepped-care" protocol, as contrasted with "referred care," on total mortality has been described in a population of 10,940 men and women by the Hypertension Detection and Follow-up Program (HDFP). [23] For persons in the age group 30 to 49 years at entry, the difference in total mortality was 5.7%; for persons aged 50 to 59 years it was 25.3%. [24] The Australian National Blood Pressure Study, a placebo-controlled primary prevention trial in 3,427 men and women with mild hypertension, reported significantly fewer morbid and fatal events, including significantly fewer deaths from cardiovascular disease, in persons aged 30 to 69 years who were treated with antihypertensive medication, but the corresponding percentage difference for all endpoints in the subgroup of men aged 30 to 49 years, though similar in magnitude, lacked statistical significance. [25] The earlier classic report from the Veterans Administration Cooperative Study concluded that treatment was effective in preventing congestive heart failure and stroke, but no statistically significant benefit for CHD mortality (six in the treated group, 11 in the placebo group) was found. [26]
In the area of lipid-lowering diet, some controversy has existed for years as to precise benefits, although most scientific including public health groups have concluded that benefits do indeed exist. [27-29] For example, the Los Angeles Veterans Administration Study, in a population of 846 institutionalized men aged 55 years and older, demonstrated significant reduction in mortality from atherosclerotic diseases, but not in total mortality. [30] The recently concluded Oslo trial in 1,232 high-risk nonhypertensive men aged 40 to 49 years combining lipid-lowering dietary intervention with smoking cessation showed statistically significant reductions in sudden coronary death and in CHD incidence, and substantial, though nonsignificant, reductions in CHD and total mortality. In the Oslo study, differential quit rates for cigarette smoking were less than those achieved in the MRFIT, but serum cholesterol differences were appreciably greater. [31] An overall impression from this partial review, particularly of recent clinical trials, is that the interventions used in the MRFIT would be expected to have a beneficial effect. However, sufficient differences from MRFIT exist in study design and related factors that firm conclusions are not possible.
The second possible explanation for the nonsignificant mortality outcome in the MRFIT is that the hypothesis received a less than definitive test, and the observed differences in mortality represent chance deviations from a larger effect that this intervention program has in the population. We have noted earlier that the power of the trial was lower than projected. One way to consider this problem, now that the trial has been completed, is through the 90% CI for CHD mortality. This ranged from a favorable effect of 25% to a harmful effect of 15%, an interval that includes the 22% benefit projected from the observed risk factor changes. A related approach is to compute the probability of observing a CHD mortality rate differential of 7.1% or less, given the observed mortality rate in the UC (19.3 deaths per 1,000) and the mortality reduction projected from the observed risk factor reduction (22%). This probability is.12, indicating that the observed result is not inconsistent with a hypothesized 22% mortality differential; however, it suggests that an effect of this magnitude is unlikely.
The third possible explanation, that some aspect of the intervention program has a deleterious effect on mortality in some subgroups, has been extensively investigated. Thus, we observed that the men who stopped smoking cigarettes were considerably less successful in weight control than were men who continued to smoke, [8] yet against any important negative influence was the finding that weight reduction was greater, overall, for SI than UC men. [7] Also, diuretics seem to increase the level of plasma cholesterol, and men who took such drugs (including nearly all hypertensive men in the SI group) had a blunting of the dietary hypocholesterolemic effect such that they achieved only about half of the cholesterol-lowering seen in men not receiving these drugs and a modest elevation of plasma triglyceride levels. [32-34] While it might be reasonable to conclude that a lessened lipid-lowering might mean a lessened improvement in CHD, CVD, and total mortality, one could hardly conclude that this effect actually increased mortality.
Another possibility, namely, that other aspects of drugs used in the treatment of hypertension in MRFIT contributed to an increased mortality, was explored. It was noted that among those hypertensive at baseline (and therefore most likely to have antihypertensive drug therapy), intervention did not result in an appreciable difference in number of deaths from CHD in the two groups (80 SI deaths and 79 UC deaths). When examined further, it seemed that the largest percentage increase in CHD mortality for SI compared with UC occurred in men with hypertension at entry whose baseline-resting ECGs showed signs of abnormalities. These findings are not conclusive, but the possibility that the use of pharmacologic therapy in these subgroups is associated with an increased CHD mortality warrants further investigation.
In some contrast with the ambiguous but disquieting results in those with hypertension are the findings in other subgroups. Here again, we mention that such subgroup data are cited with awareness of their limitations and to indicate trends and avenues for future study. Among those not hypertensive at baseline, but of course possessing other risk factors, there were 35 deaths from CHD in the SI men and 45 deaths in the UC group. Furthermore, examination of the mortality data for men with serum cholesterol values of 250 mg/dL or more at the first screening visit, but without hypertension, revealed 18 deaths from CHD in the SI group and 33 in the UC group. Similarly, among those who were cigarette smokers at baseline but were not hypertensive, there were 31 coronary deaths in the SI category and 40 among the UC men. There is therefore a pattern, at least for CHD mortality, suggesting that among those MRFIT men free of hypertension at baseline, life-style changes may result in favorable reductions in mortality.
Thus, of the possible interpretations of the mortality results, the last discussed-a combination of favorable and unfavorable effects of the intervention program-seems most plausible. Even with the unexpected sizable risk factor reduction among the UC men, the lower-than-expected UC mortality, and the duration of intervention averaging only seven years, the likelihood that these factors resulted in missing an overall positive effect is relatively low. The data suggest that, except for some groups of hypertensive persons, particularly those with resting ECG abnormalities, the MRFIT intervention is apparently associated with a lower CHD mortality in the SI group.
In conclusion, we have shown that it is possible to apply an intensive long-term intervention program against three coronary risk factors with considerable success in terms of risk factor changes. The overall results do not show a beneficial effect on CHD or total mortality from this multifactor intervention. These results are accompanied by an apparent heterogeneity of effects among sizable subgroups, but there must be caution in reaching conclusions from such subgroup data. It may be relevant that multifactor intervention received a less than optimal test owing, in part, to unexpected declines in risk factor levels and, in part, to lower-than-expected mortality in the UC group. In regard to the former, the UC men thus constituted to a considerable extent a "treated" group.
The SI-UC comparisons indicate that among men with normal baseline ECGs, the MRFIT intervention program may have had a favorable effect on CHD mortality. The data also suggest that men with hypertension, primarily those with resting ECG abnormalities, had no favorable, and possibly an unfavorable response to intervention. More study is required to clarify this issue and its possible relation to antihypertensive treatment. Findings also include the with in-group observation that men who stopped cigarette smoking had lower CHD and total mortality than those who continued to smoke.
The results of this trial do not address the possible effects of risk-factor intervention carried out over time periods of a decade or more or those begun before middle age. Future publications will address the morbidity results of the trial, subgroup hypotheses, and the role of other major variables.
The following companies supplied drugs used in this study: Ciba-Geigy Corporation-hydrochlorothiazide (Esidrex), hydralazine (Apresoline), and guanethidine (Ismelin) sulfate; USV Pharmaceutical-chlorthalidone (Hygroton); Ayerst Laboratories-propanolol (Inderal).
The principal investigators and senior staff of the clinical, coordinating and support centers, the NHLBI, and members of the MRFIT Policy Advisory Board and Mortality Review Committee are as follows:
Steering Committee
O. Paul, MD (chairperson) American Health Foundation, Mahoney Institute for Health Maintenance, New York
C. B. Arnold, MD, MPH (principal investigator), R. Mandriota, MS, MEd, R. P. Ames, MD, J. Ruff Eisenbach, RN, E. Bohm
Boston University, Boston: H. E. Thomas, Jr, MD (principal investigator), W. B. Kannel, MD (co-principal investigator), R. Rotondo, MA, J. Connors, RD, F. N. Brand, MD, L. K. Smith, MD, M. T. Prisco, RN, P. Greene, MA
Cox Heart Institute, Kettering, Ohio: P. Kezdi, MD (principal investigator), E. L. Stanley, MD (co-principal investigator), W. L. Black, MD, F. A. Ernst, PhD, E. J. Case, RN, MS, V. Bentley, D. Covert, MS, M. Lucius, RD, MEd, F. Paris, R. Semmett, L. Skotko
Dade County Department of Public Health, Miami: G. Christakis, MD, MPH (principal investigator), J. M. Burr, MD (co-principal investigator), T. A. Gerace, PhD (co-principal investigator), M. E. Wilcox, RD, MEd, D. Bramson, RD, MS, J. Benezra, MEd, J. Weddle, J. Kaye, MEd, M. Padron
Dalhousie University (MRFIT ECG Center), Halifax, Nova Scotia, Canada: P. M. Rautaharju, MD, PhD (principal investigator), H. Wolf, PhD, Harvard University, Boston, R. C. Benfari, PhD (principal investigator), K. M. Mclntyre, MD, JD (co-principal investigator), O. Paul, MD (co-principal investigator), E. Danielson, MA, J. Ockene, PhD, D. Kousch-Howard, RN, A. D. Baldwin, MD
Kaiser Foundation Research Institute, Portland, Ore: J. B. Wild, MD (principal investigator), M. Greenlick, PhD (co-principal investigator), J. Grover, MD (co-principal investigator), S. Lamb, J. Bailey, J. Dyer, MPH, B. Brokop, RN, V. Stevens, PhD, G. Bailey, RN
Lankenau Hospital, Philadelphia: W. Holmes, PhD (principal investigator), J. E. Pickering, MD (co-principal investigator), J. Allaire, MEd, E. L. Duffy, RD, D. Fellon, RN, B. Feinstein, MSA, D. Hutchins, MD, G. Rubel, RD
National Center for Disease Control, Atlanta: G. R. Cooper, PhD, MD (principal investigator), D. D. Bayse, PhD, D. T. Miller, PhD, A. Hainline, Jr, PhD, M. Kuchmak, PhD, D. A. Wiebe, PhD, C. L. Winn, L. Taylor, B. L. Botero, J. B. Gill, Jr
New Jersey Medical School, Newark: N. L. Lasser, MD, PhD (principal investigator), N. Hymowitz, PhD (co-principal investigator), K. C. Mezey, MD, B. Munves, PhD, E. Parell, RD, S. Burgio, MS, RD, V. Lasser, MA, RD, B. Johnson, S. Jeffrey, E. Rice
Northwestern University, Chicago: J. Stamler, MD (principal investigator), D. Moss, MS, V. Persky, MD, E. Robinson, MS, L. Van Horn, MA, RD, K. Shannon, MA, D. Meyers, MD
University of Chicago: L. Cohen, MD (principal investigator), J. Morgan, PhD (co-principal investigator), G. Grundmann, MS, RD, T. D. Vestal, PA, B. Huang
St Joseph's Hospital, Chicago: D. M. Berkson, MD (principal investigator), G. Lauger, MS, S. Grujic, MD, D. Obradovic, MD, E. Pardo, S. Dua, MS, S. McGowan
Institutes of Medical Sciences-University of California, San Francisco and Berkeley: J. Billings, PhD, MPH (principal investigator), S. B. Hulley, MD, MPH (co-principal investigator), W. M. Smith, MD, MPH (co-principal investigator), S. L. Syme, PhD (co-principal investigator), R. Cohen, MS, L. Dzvonik, MA, RD, L. Roos, M. Kahn, RN
Institutes of Medical Sciences, San Francisco Central Laboratory, San Francisco: G. M. Widdowson, PhD (co-principal investigator), G. Z. Williams, MD (co-principal investigator), S. B. Hulley, MD, MPH (co-principal investigator), M. L. Kuehneman (laboratory manager)
Rush-Presbyterian-St Luke's Medical Center, Chicago: J. A. Schoenberger, MD (principal investigator), J. C. Schoenenberger, PhD, R. B. Shekelle, PhD, G. S. Neri, MD, T. Dolecek, MS, RD, E. Betz, RD, L. Skweres, RD, F. Oppenheimer, RD, N. Gernhofer, MS, RD, G. G. Hardy, E. McGill, RN, Y. Hall, MS
Rutgers Medical School, Piscataway, NJ: N. H. Wright, MD, MPH (principal investigator), S. A. Kopel, PhD (co-principal investigator), K. R. Suckerman, PhD, M. Schorin, MPH, RD
St Louis Heart Association, St Louis: N. Simon, MD (principal investigator), J. D. Cohen, MD (co-principal investigator), E. Bunkers, RD, B. Ronchetto, RN, E. Grodsky, A. Fressola, J. Daniel-Gentry, MS, RN, R. Treiman, MD, W. Sullivan, MD
University of Alabama in Birmingham: H. W. Schnaper, MD (principal investigator), G. H. Hughes, PhD (co-principal investigator), A. Oberman, MD, C. C. Hill, PhD, R. Allen, PA, C. Bragg, RD, S. Stokes, RD, P. Johnson
University of California, Davis: N. O. Borhani, MD (principal investigator), C. Sugars, RD, K. Kirkpatrick, M. Lee, MD, S. DeBourelando, MPH, RD, F. LaBaw, RN, J. Turner-Tucker
University of Maryland, Baltimore: R. W. Sherwin, MB, BChir (principal investigator), M. S. Sexton, PhD, MPH (co-principal investigator), N. E. Cusack, RD, Q. T. F. de Barros, MS, P. C. Dischinger, PhD, J. Fox Spizler, MS, J. D. Heiner, MD, M. B. Pilkington, RN, MSN, B. L. ScanIon, MA
University of Minnesota, Minneapolis: R. H. Grimm, Jr, MD, MPH (principal investigator), M. Mittelmark, PhD (co-principal investigator), R. S. Crow, MD (co-principal investigator), H. Blackburn, MD (co-principal investigator), D. Jacobs, PhD (co-investigator), D. Rains, MS, M. McDonald, RN, MS, K. Lenz
University of Minnesota ECG Coding Center, Minneapolis: R. J. Prineas, MB, PhD (director), R. C. Crow, MD (associate director)
University of Minnesota, Nutrition Coding Center, Minneapolis: I. M. Buzzard, PhD (director), P. V. Grambsch (former director), J. Wenz, MS (associate director)
University of Minnesota Coordinating Center, Minneapolis: M. O. Kjelsberg, PhD (principal investigator), G. E. Bartsch, ScD (co-principal investigator), J. D. Neaton, MS (co-principal investigator), B. M. Aus, J. Bendickson, S. K. Broste, MS, J. E. Connett, PhD, A. G. DuChene, D. A. Durkin, D. L. Gorder, MS, P. V. Grambsch, G. A. Grandits, MS, D. H. Hultgren, A. Knickerbocker, W. L. Rasmussen, K. H. Svendsen, MS, L. Wille
University of Pittsburgh: L. H. Kuller, MD, DPH (principal investigator), R. McDonald, MD (co-principal investigator), A. Caggiula, PhD (co-principal investigator), L. Falvo-Gerard, MN, MPH (co-principal investigator), E. Meilahn, MPH, N. C. Milas, RD, MS, R. Russell, RD, DPH, J. Horbiak, RD, MPH, M. Alman, RN, K. Southwick, ASCP, R. Moyer, E. Gahagan
University of South Carolina, Columbia: W. K. Giese, PhD (principal investigator), J. F. Martin, MD (co-principal investigator), J. A. Keith, PhD (co-principal investigator), H. H. Harrison, RN, D. E. Mathis, MAT, C. K. Brown
University of Southern California, Los Angeles: E. Fishman, MD (principal investigator), L. Wampler, PhD, G. Newmark, MA, RD, F. Rosenfield, MPH, S. Siddiqui, MD, W. Savage, MS, RD, A. Bradford, MS, RD
Policy Advisory Board: W. Insull, Jr, MD (chairperson), J. W. Farquhar, MD, C. D. Jenkins, PhD, E. Rapaport, MD, D. J. Thompson, PhD,
H. A. Tyroler, MD, P. W. Willis III, MD, W. T. Friedewald, MD, W. Zukel, MD
Mortality Review Committee: J. T. Doyle, MD (chairman), H. B. Burchell, MD, P. N. Yu, MD, P. W. Willis III, MD (former member)
National Heart, Lung, and Blood Institute Staff, Bethesda, Md: W. T. Friedewald, MD (program director), C. D. Furberg, MD (project office director), J. A. Cutler, MD (scientific project officer), W. J. Zukel, MD (former program director), E. R. Passamani, MD (former scientific project officer), C. T. Kaelber, MD (former scientific project officer), M. E. Farrand, RD, MS, J. L. Tillotson, RD, MA, J. I. Verter, PhD, M. C. Wu, PhD, T. Gordon, M. Halperin, PhD, D. L. McGee, PhD, T. P. Blaszkowski, PhD, K. A. Eberlein, MPH, C. E. Harris, P. L. Dern, MD, L. M. Friedman, MD, G. S. May, MB, BChir, A. J. Vargosko, PhD
Reprint requests to MRFIT Coordinating Center, Biometry Division, University of Minnesota, School of Public Health, Room 508, 2829 University Ave SE, Minneapolis, MN 55414 (Marcus O. Kjelsberg, PhD).
1. US Dept of Health, Education, and Welfare. Arteriosclerosis: A Report by the National Heart and Lung Institute Task Force on Arteriosclerosis, vol 1. US Dept of Health, Education, and Welfare publication No. (NIH) 72-137. Washington, DC, National Institutes of Health, 1971. [Context Link]
2. Zukel WJ, Paul O, Schnaper HW:. The Multiple Risk Factor Intervention Trial (MRFIT): I. Historical perspectives. Prev Med 1981;10:387-401. [Medline Link] [Context Link]
3. Sherwin R, Kaelber CT, Kezdi P, et al. The Multiple Risk Factor Intervention Trial (MRFIT): II. The development of the protocol. Prev Med 1981;10:402-425. [Medline Link] [Context Link]
4. The Multiple Risk Factor Intervention Trial Group. The Multiple Risk Factor Intervention Trial Group: Statistical design considerations in the NHLI Multiple Risk Factor Intervention Trial.. J Chronic Dis. 1977;30:261-275. [Medline Link] [Context Link]
5. Rose GA, Blackburn H, World Health Organization Monograph Series. Cardiovascular Survey Methods. No. 56 Geneva, 1968. [Context Link]
6. Benfari RC. The Multiple Risk Factor Intervention Trial (MRFIT): III. The model for intervention. Prev Med 1981;10:426-442. [Medline Link] [Context Link]
7. Caggiula AW, Christakis G, Farrand M, et al. The Multiple Risk Factor Intervention Trial (MRFIT): IV. Intervention on blood lipids. Prev Med 1981;10:443-475. [Medline Link] [Context Link]
8. Hughes GH, Hymowitz N, Ockene JK, et al. The Multiple Risk Factor Intervention Trial (MRFIT): V. Intervention on smoking. Prev Med 1981;10:476-500. [Medline Link] [Context Link]
9. Cohen JD, Grimm RH Jr, Smith WM. The Multiple Risk Factor Intervention Trial (MRFIT): VI. Intervention on blood pressure. Prev Med 1981;10:501-518. [Medline Link] [Context Link]
10. Butts WC, Kuehneman M, Widdowson GM. Automated method for determining serum thiocyanate to distinguish smokers from nonsmokers. Clin Chem 1974;20:1344-1348. [Medline Link] [Context Link]
11. US Dept of Health, Education, and Welfare. Manual of Laboratory Operations, vol 1, Lipid Research Clinics Program. US Dept of Health, Education, and Welfare publication No. DHEW (NIH) 75-628. Washington, DC, National Institutes of Health, 1974. [Context Link]
12. Blackburn H. Measurement in Exercise Electrocardiography. Springfield, Ill, Charles C Thomas Publisher, 1969. [Context Link]
13. Neaton JD, Broste S, Cohen L, et al. The Multiple Risk Factor Intervention Trial (MRFIT): VII. A comparison of risk factor changes between the two study groups.. Prev Med 1981;10:519-543. [Medline Link] [Context Link]
14. Dennis B, Hjortland M, et al:. The NHLBI nutrition data system.. J Am Diet Assoc. 1980;77:641-647. [Medline Link] [Context Link]
15. Eisinger RA. Psychosocial predictors of smoking behavior change.. Soc Sci Med.1972; 6:137-144. [Medline Link] [PsycINFO Link]
16. Kaplan E, Meier P. Non-parametric estimation from incomplete observations.. J Am Stat Assoc. 1958;53:457-481.
17. Mantel N. Evaluation of survival data and two new rank order statistics arising in its considerations.. Cancer Chemother Rep. 1966; 50:163-170. [Medline Link] [Context Link]
18. Bross I. A confidence interval for a percentage increase.. Biometrics. 1954;10:245-250. [PsycINFO Link] [Context Link]
19. National Institutes of Health. Report of the Working Group on Arteriosclerosis of the National Heart, Lang, and Blood Institute: Arteriosclerosis 1981, vol 2. NIH publication 82-2035. Bethesda, Md, National Institutes of Health, 1981. [Context Link]
20. Rose G, Hamilton PJS, Colwell L, et al. A randomised controlled trial of antismoking advice: Ten-year results.. J Epidemiol Community Health. 1982;36:102-108. [Medline Link] [Context Link]
21. Kuller L, Meilahn E, Townsend M, et al. Control of cigarette smoking from a medical perspective.. Ann Rev Public Health. 1982;3:153-178. [Medline Link] [Context Link]
22. Rogot E, Murray JL. Smoking and causes of death among US veterans: 16 years of observation.. Public Health Rep. 1980;95:213-222. [Medline Link] [Context Link]
23. Hypertension Detection and Follow-up Program Cooperative Group. Five-year findings of the Hypertension Detection and Follow-up Program: I. Reduction in mortality of persons with high blood pressure, including mild hypertension. JAMA 1979;242:2562-2571. [Medline Link] [Context Link]
24. Hypertension Detection and Follow-up Program Cooperative Group. Five-year findings of the Hypertension Detection and Follow-up Program: II. Mortality by race-sex and age. JAMA 1979;242:2572-2577. [Medline Link] [Context Link]
25. Report by the Management Committee: The Australian Therapeutic Trial in Mild Hypertension.. Lancet. 1980;1:1261-1267. [Context Link]
26. Administration Cooperative Study Group on Antihypertensive Agents. Effects of treatment on morbidity in hypertension: II. Results in patients with diastolic blood pressure averaging 90 through 114 mm Hg. JAMA 1970;213:1143-1152. [Medline Link] [Context Link]
27. Report of Inter-Society Commission for Heart Disease Resources: Primary prevention of the atherosclerotic diseases.. Circulation. 1970; 42:A55-A95. [Context Link]
28. Grundy SM, Bilheimer D, Blackburn H, et al. Rationale of the diet-heart statement of the American Heart Association, Report of Nutrition Committee.. Circulation. 1982;65:839A-854A. [Context Link]
29. Stamler J. Lifestyles, major risk factors, proof and public policy.. Circulation. 1978;58:3-19. [Medline Link] [Context Link]
30. Dayton S, Pearce ML, Hashimoto S, et al. Controlled clinical trial of a diet high in unsaturated fat in preventing complications of atherosclerosis.. Circulation. 1969;39/40(suppl 12):1-63. [Context Link]
31. Hjermann I, Velve Byre K, Holme I, et al. Effect of diet and smoking intervention on the incidence of coronary heart disease, report from the Oslo Study Group of a Randomized Trial in Healthy Men.. Lancet. 1981;2:1303-1310. [Medline Link] [Context Link]
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Cholesterol; Coronary Disease; Hypertension; LANDMARK ARTICLES; Nutrition; Risk Factors; Smoking


text:
Getting Started
You've got an awesome mod and now you want to allow millions of Curse Client users to install it without any hassles. For games where all the mods sit together in the same folder, we've created Curse Mod 2 (CMOD2) and a packaging tool built-in to the Curse Client to help make packaging your mods easy.
About Curse Mod 2
Curse Mod 2 (CMOD2) is a standard ZIP archive where the files inside are organized so they can be easily copied from the ZIP into the game's mod folder. In a non-CMOD2 ZIP you may have all your files in the root and use a readme file to desribe to the user where each file goes. CMOD2 allows you to strictly define where the file should go relative to the mod folder.
CMOD2 also lets users customize how the files will be installed using a simple scripting engine, powered by JavaScript. With the scripting engine you can modify parts of an XML file, copy optional files, and more.
Packaging Your Files
- To package your files, you'll need to download and install the Curse Client: http://www.curse.com/client
- Once installed and logged in, you should see a list of your installed games on the left. Select the game you want to package your mod for. For this example, we'll be using The Secret World.
- Select Tools > Create a Package
- Select "Create a Mod Package"
Note: After you've created your first package, you can come back and open it when you have an update ready. This will let you swap out the updated files without recreating the entire package.
- If you already have a ZIP of your mod, you can click "Add Archive" to
import everything you need. Otherwise, you can add files manually or add an
entire folder.
By default, your readme and some other files will be unchecked. This means they will be in the ZIP, but wont be copied into the game folder. This allows users who download the file without the Curse Client to still have the readme but not clutter up the game folder for those who do use the Curse Client.
You may have noticed that for The Secret World, "*Prefs.xml" and "Modules.xml" are unchecked. This is because the user probably already has these files from other mods so we'll need to script this part. Leave the files in the package unchecked so non-Curse Client users can still use them.
- You should have all your files inside the list now. It probably looks
something like this:
- Everything is at the root so far, but we need the .swf files to go
inside of a folder. To do this, we simply select the file in the list and
add the folder path to the begining of the file. For mine, I add "Flash\"
- Click Next to License Agreement
- You can provide a license agreement to the user if you want to emphasis copyright and usage terms. If you enter a license agreement, it'll be required for the user and they will be prompted when they install / updated the mod.
- Click Next to Scripting
- Because this is a TSW mod, we need to update 2 XML files, to do this
will be using the "xmlCreateOrUpdate" API - This allows us to insert an XML
element into an existing file. If the file doesn't exist, it'll create one
for us.
xmlCreateOrUpdate('CharPrefs.xml', '/Root', '<Value name="TSWRPCharacterViewer" value="true"/>');
In the API, we're telling the Curse Client the file we want to create or update, the XPath of where the element will go, and finally the element string that will be inserted. We call this method for each element we wanted to add.
- Click Next and save your package. Tip: It's best to save the package as the same name as your mod - You can leave any version information out if you want.
- Now head on over to http://tsw.curseforge.com and upload your file like normal. Our team of moderators will need to approve the file before users can start installing it from the Curse Client.
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- Date created
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- Last updated
- Sep 11, 2013

subset: commoncrawl


text:
Safety is one of our top priorities at Summit Natural Gas.
Employees from the Hollister/Branson office presented a safety training seminar for the Western Taney County Fire Department last Thursday 8-15-13.
Summit Natural Gas recently sponsored the August Luncheon for the Hollister Area Chamber of Commerce.
Below are some photos from the event.
Crews will be testing and opening up gas lines for use in Camdenton and Linn Creek in the following weeks.
Customers with a service line will be called to schedule their conversion appointment.
Summit Natural Gas launched our new website earlier this week!
Representatives from Summit attended MEDA Day at the Capital this past Wednesday.Summit joined other utility and energy companies to spread awareness about their organizations.
Each week KRMS and JJ's at the Copper Pot team up to host the West Side Social.Last night our SNG Lake of the Ozarks Office hosted the fun event to mingle with locals and business owners.
More News | View Blog
Safety is of the highest importance in the natural gas industry. If you believe you have a natural gas emergency, call 855-460-0021.
Read More About Natural Gas Safety
-Mike Kenagy, Executive DirectorLake West Chamber of Commerce
Read More Testimonials


text:
Canada Welcomes Nomination of Luis Alberto Moreno for Second Term as Inter-American Development Bank President
(No. 174 - May 26, 2010 - 12:10 ET) The Honourable Lawrence Cannon, Minister of Foreign Affairs, and the Honourable Peter Kent, Minister of State of Foreign Affairs (Americas), today welcomed the nomination of Luis Alberto Moreno for a second term as president of the Inter-American Development Bank (IDB). The minister of foreign affairs is Canada's IDB governor.
"Canada fully supports Colombia's nomination of Luis Moreno to a second term as president of the Inter-American Development Bank," said Minister Cannon. "Canada is an active member of the IDB and values its partnership with the Bank in the delivery of our common social and economic development objectives for the region. As president of the IDB, Mr. Moreno has played an instrumental role in mobilizing significant Bank resources to assist the region in mitigating the effects of the global economic and financial crisis."
"Mr. Moreno is the best individual to lead the IDB during this critical period," said Minister of State Kent. "I'm confident his dynamic leadership and in-depth understanding of the region's economies will continue to generate prosperity throughout the hemisphere."
Mr. Moreno was elected president of the IDB in July 2005 and took office on October 1, 2005. His current, five-year term will expire on September 30, 2010.
Canada will host the 2011 annual general meeting of the IDB in Calgary, Alberta.
For more information, please consult Canada's partnership with the Inter-American Development Bank.
- 30 -
For further information, media representatives may contact:
Catherine Loubier
Director of Communications
Office of the Minister of Foreign Affairs
Meredith McDonald
Senior Communications Adviser
Office of the Minister of State of Foreign Affairs (Americas)
Foreign Affairs Media Relations Office
Foreign Affairs and International Trade Canada
- Date Modified:


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Earlier this year we bought a vacation home in Las Vegas.
I don't know many folks in the neighborhood, but last week I did meet a neighbor who recently moved from Huntington Beach.
I asked Jeff Abraham, 56, why he'd left Orange County. I wasn't prepared for the story he was about to tell me.
Orange County held too many memories for him of a senseless murder.
Abraham's friend and business partner, urologist Dr. Ron Gilbert, was killed Jan. 28 at Hoag Hospital in Newport Beach.
"Ron was assassinated," he said.
Stanwood Elkus., 75, of Lake Elsinore was arrested on suspicion of fatally shooting Gilbert as he walked into an examination room. Eklus has pleaded not guilty and remains in jail awaiting trial.
Abraham said it was a case of mistaken identity. Gilbert's name was close to that of a doctor who'd treated Elkus for years, he said. It was Gilbert's first time seeing Elkus, he said.
What makes Gilbert's story even more tragic is that the day before he was killed, he and Abraham received a $30 million offer for the company they'd built based upon Gilbert's discovery of a new drug to treat premature ejaculation, also known as PE.
To give you some background, Abraham, Gilbert, and their families had been friends for 18 years.
The two met when Abraham's urologist retired, and Gilbert bought the practice.
In 2011 Gilbert asked Abraham for business advice on Absorption Pharmaceuticals, a company he'd started in 2009.
Gilbert's company started marketing Promescent, the PE drug he developed, in 2010.
"He asked me to review his company. I was retired and bored so I wrote him a business plan," Abraham said.
Impressed with Gilbert's new drug, Abraham invested in the company, and in June 2011 became its CEO.
An estimated one in every three men suffer from premature ejaculation, according to the Mayo Clinic website. Treatment typically consists of anti-depressants, but side effects can include nausea, dry mouth, drowsiness and lower libido, experts said.
Comments are encouraged, but you must follow our User Agreement
Keep it civil and stay on topic. No profanity, vulgarity, racial slurs or personal attacks. People who harass others or joke about tragedies will be blocked. By posting your comment, you agree to allow Orange County Register Communications, Inc. the right to republish your name and comment in additional Register publications without any notification or payment.


text: Classes & Events Woman's offers a large variety of classes & programs for women and their families during all stages of life. Topics range from pregnancy and parenting to wellness and nutrition and many topics in between - all focused on a healthy, fulfilling life. All upcoming dates are listed on the class page below class description. Most classes are held at Woman's Hospital or Woman's Center for Wellness. Refund Policy: A refund, less a $10 administrative fee, will be issued up to 7 working days before the class date. A refund will not be issued for cancellations received within 7 working days of the class.


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Makeover is not a great place by any means. The service isn't bad but the girls are not good looking (read ugly). And I don't like the little cubicle with its teeny massage bench. Zamai, too, is a mediocre experience. The Oxygen place near the mazar is pathetic while the other Oxygen on Bukhari is a hit or miss proposition.
Liquid, it would be great if you'd comment on the others.


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Stronger Together: The Value of Association
By David Adams
MCUL & Affiliates CEO
Since the latter part of 2011, there has been tremendous momentum driving consumers to take a closer look at credit unions, and that momentum continues to build as we move into the second half of 2012. With the economy slowly improving on several fronts, now is a time of opportunity for credit unions of all sizes.
Recently, we hit a major milestone: for the first time ever, 4.5 million people are now members of Michigan credit unions. That includes 25,000 new members who joined in the first quarter of the year alone. Deposits are up and there is loan growth in autos, small businesses and first mortgages. Good things are happening in our state, and credit unions play a big part.
It's the continued spirit of cooperation that keeps all credit unions – especially SAS credit unions, invested in the needs of their members and the growth of the movement, and continues to drive the industry and our state forward. We know that SAS credit unions face a particular set of challenges, and as your association we strive to help you meet those challenges.
There's no better example of that than our CU Difference campaign, which this year is larger than ever. By pooling the collective resources of our credit unions, everyone, large and small, benefits from the increased exposure and advertising.
The Michigan Credit Union Foundation is another example of pooled resources which benefit the community as a whole. As you'll read in this issue, the foundation provides specific support to SAS credit unions for educational development and operational grants. Annual donations of even a small amount help make these opportunities possible.
In this issue you'll also find timely compliance information regarding changes to Michigan's durable power of attorney law, details of a new lapel program exclusively for SAS credit unions, and the inspiring story of one SAS credit union leader who made a very big impact when she traveled to the other side of the world to share her expertise with women in Africa.
As a member of the MCUL & Affiliates and our movement, you are part of something bigger than any one institution, large or small. Individually, we have our strengths, but together we can't be beat.


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Black pyramid art installation delivers power for 250 homes
Some people believe pyramids have mysterious powers, but those beliefs could become real if this solar pyramid array in Abu Dhabi ever gets built.
Lunar Cubit is the winning entry in Land Art Generator Initiative, a contest in the UAE for designing beautiful green energy installations.
With one central pyramid surrounded by eight smaller versions representing the eight phases of the moon, the Lunar Cubit pyramids light up in various combinations to indicate the current moon phase. There's also some kind of tie in to the Islamic calendar and even Einstein, but that gets a bit to deep for me. The deep black color comes from the solar panels covering each surface, and which can deliver enough power for up to 250 homes.
While Lunar Cubit is just a concept, the UAE has a strong track record for building some pretty crazy stuff, so there is always a chance that it might actually get built.
Lunar Cubit, via Fast Code Design


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Student essay and art contests are being held locally as part of Michigan Week celebrations in May.
Organizers of local Michigan Week events are asking Monroe County students in the sixth through eighth grades to enter the essay contest with the topic "Why is the River Raisin National Battlefield important for Monroe County?"
An art contest also is being held for students in kindergarten through fifth grade. The theme is the River Raisin National Battlefield.
The deadline to submit materials is May 17.
For more information, call 242-2103.
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Jabil Posts Fourth Quarter & Fiscal Year 2012 Results
Today Jabil Circuit, Inc. (NYSE:JBL), announced its preliminary, unaudited financial results for the fourth quarter and full fiscal year, ended August 31, 2012. The company reported fourth quarter revenue of $4.3 billion and fiscal year revenue of $17.2 billion. "In this environment, posting another record fiscal year in revenue, income and earnings was quite an achievement," said Timothy L. Main, President and CEO of Jabil.
Market share gains, new customer wins and new production from existing customers allowed Jabil to grow its targeted markets during the fiscal year while most of the industry contracted. Jabil's Diversified Manufacturing Services business grew 24 percent in fiscal 2012. Although Jabil picked up share gains in its Enterprise & Infrastructure business during the year, overall demand weakened, resulting in a decrease of 2 percent from fiscal 2011. Jabil's High Velocity business declined 14 percent during the fiscal year.
"Results for the fourth quarter were negatively impacted by a challenging new program ramp in our Specialized Services sector," said Main. "Additionally demand remained weak in most of our business segments." Generally accepted accounting principles (GAAP) operating income for the quarter was $144 million. These results were negatively impacted by a distressed customer charge of $5.9 million. Excluding amortization of intangibles, stock-based compensation and distressed customer charges, operating income was $175 million. GAAP diluted earnings per share was $0.39 cents and core diluted earnings per share was $0.54 cents.
"We are pleased to have generated cash flow from operations of $443 million during the quarter and $634 million over the course of the year. Due to this outstanding performance and ongoing strength of the balance sheet, we were able to return $136 million in capital to shareholders during the fiscal year through dividends and share repurchases," said Chief Financial Officer Forbes Alexander. "We see this positive performance continuing and are estimating operating cash flow of $1 billion in fiscal 2013," Alexander noted.
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Tees & Tanks
mouse over photo to zoom click for larger image
Vibe V Tee
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Johnson & Johnson Postpones Medical Devices & Diagnostics Review
NEW BRUNSWICK, N.J., Oct. 30, 2012 /PRNewswire/ -- Given the state of emergency in New Jersey due to Hurricane Sandy, Johnson & Johnson (NYSE: JNJ) announced that it will postpone the company's Medical Devices & Diagnostics business review for the investment community, which was scheduled for Thursday, Nov. 1 st. The company made the postponement decision to ensure the safety of its employees and expected attendees in the aftermath of the storm. A new date for the business review will be scheduled for early 2013.
About Johnson & Johnson
Caring for the world, one person at a time…inspires and unites the people of Johnson & Johnson. We embrace research and science - bringing innovative ideas, products and services to advance the health and well-being of people. Our approximately 129,000 employees at more than 250 Johnson & Johnson operating companies work with partners in health care to touch the lives of over a billion people every day, throughout the world.
SOURCE Johnson & Johnson
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also see:
nearby alternative beer places
nearby bed & breakfasts
nearby hotels (w/reservations online)
nearby historic landmarks
nearby restaurants
Beer Guide for Coral Springs, FL
Beer Guide for Florida
DUI lawyer
DWI lawyer
gift certificates
homes for sale
houses for rent
local bands
web hosting
Burgers and Pizza were good.
The beers at the Bear are the best and the Hybrination Pale Ale cannot be beat! From Maine to Oregon, down to California and back home to Florida, I have searched for a better pale ale...draft or bottled-The Bear beats them all!
AND-the service is great, especially Kelley....
BUT-Please, put the kiddies someplace else, this is my favorite place for a relaxing draft and the ever increasing number of little sereemers in the bar area is out of control!
I was once a member of the Big Bear mug club, but I never found a reason to continue that relationship. The beer is flat and flavorless. The best on tap is probably the brown, but it is nothing exceptional. Don't dare request hops in this place.
The food is good, not great. Big Bear caters to a clientelle that cares more about wine than beer, and it shows. Head down the road to the ale house or wing place, where at least you'll get a Whitbread than something that tastes like it was brewed by a novice.
Frank Gibson Coral Springs, FL
The beers are served in the appropiate pilsners or pint mugs and at the appropiate temperatures. They are all delicious! The best Rootbeer (house brewed) in South Florida without question.
Outstanding beer / cheese soup served in a bread bowl!! Great salads, good steaks and burgers,ribs, and excellent spinach dip appetizer too.
Tip: Frequently they produce some seasonal / mgr special brews not shown on menu. Alright. Stop salivating.....
They do serve a cola called Classy Cola and Diet Classy Cola, both are excellent and it is difficult to tell the two apart. They have much more of a cola nut flavor than mass produced colas.
The stout was excellent.


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Grub Street and Top Chef's Food Truck Is Now Serving Po' Boys
It's lunchtime!
Skip to content, or skip to search.
Skip to content, or skip to search.
Gail Simmons is there!
The Top Chef food truck will hit Manhattan on October 1.
A gourmet store is giving away a laptop, among other "free stuffs."


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Villa Silvia Siracusa
Official Contact Details - Villa SilviaPhone: +39.339.2983507
Charming villa in the country with a stunning view on the sea and on Ortigia (Siracusa)
- Price from 1000 EUR / Week / Per unit
- 3 bedrooms & 2 bathrooms
(click on a photo to view it)
Last updated: 05/05/2010
This is your property ?
Villa Silvia is set on a beautiful open countryside with fabulous view of Ortigia island as far as Etna Volcano.
Its panorama is among the most beautiful of any of our villas. This, along with the peaceful location, ensures its position as one of our most desirable properties. It is located in Penisola Maddalena, close to Syracuse, and just a short drive from a sandy beach - The beach of Punta del Pero is about 5 minutes away, while Siracusa is 15 minutes away.
This villa is ideally located for exploring Syracuse and its province!
The style of the house is clean, bright and fresh, with large windows and a general feeling of space.
The villa consists of two double bedrooms (one with sea view), one twin bedroom, two bathrooms (one with shower and one with bath tub), a well designed and fully equipped kitchen (with sea view), a dining area and a large living room with white sofas. The living room has large windows with sea view and leads to a large terrace overlooking the countryside and the sea.
The house is equipped with heating, air conditioning, washing machine, Tv, DVD player, BBQ.
The entire house has been tastefully furnished and the villa enjoys a private terrace, secluded garden and parking.
Clean lines, stylish and quality furnishings and fittings, practical living, open spaces, views, and proximity to the famose seaside resorts of Fontane Bianche, Terrauzza and Arenella make this an ideal property for families or groups of friends. This villa provide private and peaceful accommodation for up to 6/7 people.
In the neighbourhood there are a little food market and several restaurants & pizzerie.
Prices & deals
- Lowest Weekly Price:
- Highest Weekly Price:
- Cleaning fee:
- Charging Method:
- Per unit
- Payment Types:
- Cash
- Credit Card
- Cheque
- Travellers cheque
- Paypal
- Wire Transfer
Location & area
Suggested for lovers of country and suggested for lovers of sea! The villa is just 10 Km from the charming Ortigia, 5 Km from a little beach and surrounded from the country! You can be sure you'll love this location!
- Address:
- Isola Maddalena - Siracusa, 96100, Siracusa, Sicily, Italy
- Accommodation located in:
- countryside, near the beach, rural!
Amenities & services
# of Units: 1... and each unit includes:
- Bedrooms: 3
- Bathrooms: 2
- Single beds: 2
- Double beds: 1
- Baby cots: 1
- Single sofa beds: 0
- Double sofa beds: 1
- Towels:
- Bath:
- Hair Drier:
- Shower:
- Telephone:
- DVD Player:
- Fax:
- Washing Machine:
- Work Desk:
- Bed Sheets:
- Bikes:
- Cable/Satelite TV:
- Internet Broadband:
- Internet Dial Up:
- Ironing Board:
- Library:
- Stereo/Radio System:
- Local Guides:
- Local Transportation:
- 24h Concierge:
- Tours & Excursions:
- House Chef:
- Butler Service:
- Dish Washer:
- Microwave:
- Oven:
- American Kitchen:
- Fridge & Freezer:
- Crockery & Utensils:
Living room
- Table & Chairs:
- Fireplace:
- Sofa Bed:
- Lift / Elevator:
- Swimming Pool:
- Disabled Facilities:
- Tennis Court:
- Terrace:
- Parking:
- Pets Welcome:
- Private Beach:
- Barbecue:
- Garden:
- Sauna:
- Shared Bathroom:
- Spa / Jacuzzi:
- Daily Cleaning:
- DVD/Music Collection:
- Air Conditioning:
- Ensuite Bathroom:
- Balcony:
- Safe:
- Sea View:
- Central Heating:
- City View:
Review - Villa Silvia
Villa Silvia - Contact the owner
Important Notice : Avoiding Fraud
It's rare, but some helpful hints to watch out for with regards to fraud:
- It is important to NEVER wire funds or use/employ other fund transfer mechanisms such as western union: Always use a credit card to protect yourself against fraud. If owners pressure you into providing a deposit or refuse to accept credit cards, there is a high probability that this is a scam.
- If at all suspicious of fraud, ask to see their website, or any other literature they can provide or send to you. Ask them for contact details for guests who have previously stayed on their property insisting on telephone numbers. Be suspicious of emails that originate from free email services (yahoo, hotmail, gmail, etc)
- Research the property thoroughly on the internet to see if there is any history or mention of scams associated with the property.


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Hundreds get free flu shots in their cars
Updated On: Nov 05 2012 06:40:13 AM EST
Hundreds of people in Baltimore County drove their way to getting prepared for the flu season.
Franklin Square Medical Center held its annual drive-through flu clinic at Essex Community College on Sunday.
By day's end, 1,800 people received free flu shots -- all without leaving their cars.
Copyright 2012 by WBALTV.com All rights reserved. This material may not be published, broadcast, rewritten or redistributed.


text:
The Global Intelligence Files,
files released so far...
Index pages
by Date of Document
Our Partners
Al Akhbar - Lebanon
Al Masry Al Youm - Egypt
Asia Sentinel - Hong Kong
Bivol - Bulgaria
Carta Capital - Brazil
CIPER - Chile
Dawn Media - Pakistan
L'Espresso - Italy
La Repubblica - Italy
La Jornada - Mexico
La Nacion - Costa Rica
Malaysia Today - Malaysia
McClatchy - United States
Nawaat - Tunisia
NDR/ARD - Germany
Owni - France
Pagina 12 - Argentina
Philip Dorling - Fairfax media contributor - Australia
Plaza Publica - Guatemala
Publica - Brazil
Publico.es - Spain
Rolling Stone - United States
Russian Reporter - Russia
Ta Nea - Greece
Taraf - Turkey
The Hindu - India
The Yes Men - Bhopal Activists
Sunday Star-Times - New Zealand
Community resources
courage is contagious
The Global Intelligence Files
On Monday February 27th, 2012, WikiLeaks began publishing The Global Intelligence Files, over five million e-mails from the Texas headquartered "global intelligence" company Stratfor. The e-mails date between July 2004 and late December 2011. They reveal the inner workings of a company that fronts as an intelligence publisher, but provides confidential intelligence services to large corporations, such as Bhopal's Dow Chemical Co., Lockheed Martin, Northrop Grumman, Raytheon and government agencies, including the US Department of Homeland Security, the US Marines and the US Defence Intelligence Agency. The emails show Stratfor's web of informers, pay-off structure, payment laundering techniques and psychological methods.
Re: keeping in touch
Released on 2012-10-05 00:00 GMT
|2011-03-29 23:20:00
Many thanks for your information you sent to me. This e-mail is to confirm
that I received your information. May I also confirm that it is correct
and permissible to call your group, in English, the Angolan Autocton
Resistance for Change (RAAM, in Portuguese)? I am now reviewing the last
e-mail that you sent me. Let me revert to you once I have had a chance to
digest your information.
Thank you again.
On 3/29/11 1:26 PM, Domingos Nzuzi wrote:
Dear Mark,
Thank you very much for your appreciation,
I believe you receive now the big information I send
to you to complete our yesterday conversation.
Thank and best regards.
Nzuzi Domingos
RAAM Secretary General.
2011/3/29 Mark Schroeder <email@example.com>
Dear Domingos:
It was excellent having our first conversation, yesterday. I look
forward to keeping in touch, and to receiving your information today.
Thank you again for your thoughts.
Mark Schroeder
Director of Sub Saharan Africa Analysis
STRATFOR, a global intelligence company
Tel +1.512.744.4079
Fax +1.512.744.4334
Email: firstname.lastname@example.com
Web: www.stratfor.com


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Big Ballas Christmas Party To Be Held on Saturday, December 20 at St. Andrew's Hall in Detroit!
We're hanging the stockings and roasting the chestnuts…oh fuck that happy Yuletide shit…this is the BIG BALLAS CHRISTMAS PARTY, MOTHERFACKO! On Saturday, December 20 at St. Andrew's Hall in Detroit, Violent J and Shaggy 2 Dope will be hosting the WICKEDEST holiday hootenanny in Detroit Murderous, featuring a full length performance by those ganja gods…the Kottonmouth Kings! There will also be a full card of blood splattering, bone crushing JCW wrestling, with appearances by all your favorite JCW grapplers including JCW World Heavyweight Champion 2 Tuff Tony, Necro Butcher, JCW Tag Team Champions The Ring Rydas, Mad Man Pondo and many more! All this flavor will be brought to you by your hosts of the evening…the INSANE CLOWN POSSE!
The Big Ballas Christmas Party goes down at St. Andrew's Hall on Saturday, December 20. Doors at 7 p.m.
Tickets available here: http://concerts.livenation.com/event/08004D71AE46379B


text:
Bugzilla – Bug 5425
Backwards compatability break in 4.0.5
Last modified: 2007-07-10 14:50:43
You need to
log in
before you can comment on or make changes to this bug.
ManagedExecutableJobConstants.RD_STAGING_JOB_ENDPOINT does
not exist anymore in Gram in GT 4.0.5
Instead, three other constants exist:
We had to change this because of audit logging in 4.0.5.
Having only one constant we had not been able to store
various endpoints of stageIn, stageOut and fileCleanup requests
which are now saved as part of an audit record.
But we forgot backwards compatability issues when we removed
that constant. A check is needed whether this constant can be added
again in a way that makes sense.
I'm resolving this. I don't think we need to worry about compatibility to this
level. This is an internal service variable that does not need to be preserved
for backward compatibility. What needs to be preserved is the service
interface and any supported client and service APIs.