lsu health care services division ( lsuhcsd ) operates seven public hospitals and affiliated clinics in louisiana , which provide quality medical care to the residents of louisiana regardless of their income or insurance coverage ( 1520 ) . overall , lsuhcsd facilities have served ~1.6 million patients ( 35% of the louisiana population ) since 1997 . administrative ( name , address , date of birth , sex , race / ethnicity , types of insurance , family income , and smoking status ) , anthropometric ( date of examination , measurements of body weight , height , and blood pressure for each visit ) , laboratory ( test code , test collection date , test result values , and abnormal flag ) , clinical diagnosis ( date of diagnosis , diagnosis code , priority assigned to diagnosis and icd-9 and current procedural terminology procedure codes ) , and medication ( medication generic name , pharmacopeia dispensable drug i d , medication strength - dose form , medication strength units , medication rote code and description , medication form , etc . ) data collected at these facilities are available in electronic form for both inpatients and outpatients from 1997 . using these data , a cohort of diabetic patients was set up by using the icd-9 ( code 250 ) through the lsuhls database between 1 january 1999 and 31 december 2009 . both inpatients and outpatients internal diabetes disease - management guidelines call for physician confirmation of diabetes diagnoses by applying the american diabetes association criteria : a fasting plasma glucose level 126 mg/ dl , 2-h glucose level 200 mg / dl after a 75-g 2-h oral glucose tolerance test , and one or more classic symptoms plus a random plasma glucose level 200 mg / dl ( 21 ) . the first record of diabetes diagnosis was used to establish the baseline for each patient in the present analyses due to the design of the cohort study . these newly diagnosed diabetic participants had benefited from lsuhcsd hospitals for 3.68  4.35 years prior to the baseline . the current study included 30,154 diabetic patients ( 12,618 whites and 17,536 african americans ) who were 3094 years of age without a history of chd or stroke and with complete repeated data on major risk factor variables . in these diabetic patients , ~78.9% of patients qualify for free care ( by virtue of being low income and uninsured  any individual or family unit whose income is 200% of federal poverty level ) , ~5.1% of patients are self - pay ( uninsured , but incomes not low enough to qualify for free care ) , ~5.1% of patients are covered by medicaid , ~8.9% of patients have medicare , and ~2.2% of patients are covered by commercial insurance . the study and analysis plan were approved by both pennington biomedical research center and lsu health sciences center institutional review boards , lsu system . we did not obtain informed consent from participants involved in our study because we used anonymized data compiled from electronic medical records . the patient s characteristics , including age of diabetes diagnosis , sex , race / ethnicity , family income , smoking status , types of insurance , body weight , height , bmi , blood pressure , total cholesterol , hdl cholesterol , ldl cholesterol , triglycerides , hba1c , estimated glomerular filtration rate ( egfr ) , and medication ( antihypertensive drug , cholesterol - lowing drug and antidiabetes drug ) , within a half year after the diabetes diagnosis ( baseline ) and during follow - up after the diabetes diagnosis ( follow - up ) were extracted from the computerized hospitalization records . blood pressure was measured from the right arm of the participant after 5 min of sitting using a mercury sphygmomanometer or electronic blood pressure meter in each visit ( 19 ) . an updated mean value of blood pressure over time was calculated for each individual from diabetes diagnosis to the final clinical measure of follow - up or to the last value before the occurrence of chd . the average number of blood pressure measurements during the follow - up period was 14.6 times . follow - up information was obtained from the lsuhls inpatient and outpatient database by using the unique number assigned to every patient who visits the lsuhcsd hospitals each time . the diagnosis of chd was the primary end point of interest of the study and was defined according to the icd-9 : chd ( icd-9 codes 410414 ) . since 1997 , diagnoses of chd were made by the treating physicians based on a clinical assessment and examinations as considered relevant by the clinician in charge of treatments . follow - up of each cohort member continued until the date of the diagnosis of chd , the date of the last visit if the subject stopped use of lsuhcsd hospitals , death , or 31 may 2012 ( 18 ) . the association between blood pressure and the risk of chd was analyzed by using cox proportional hazards models . systolic blood pressure ( sbp ) and diastolic blood pressure ( dbp ) were evaluated in the following two ways 1 ) as six categories ( sbp < 110 , 110119 , 120129 , 130139 [ reference group ] , 140159 , and 160 mmhg ; dbp < 65 , 6569 , 7079 , 8089 [ reference group ] , 90100 , and 100 mmhg ; and sbp / dbp < 110/65 , 110119/6569 , 120129/7079 , 130139/8089 [ reference group ] , 140159/9099 , and 160/100 mmhg ) , and 2 ) as a continuous variable ( sbp and dbp ) . different levels of blood pressure were included in the models as dummy and categorical variables , and the significance of the trend over different categories of blood pressure was tested in the same models by giving an ordinal numeric value for each dummy variable . all analyses were adjusted for age and sex and further for smoking , income , types of insurance , hba1c , ldl cholesterol , egfr , use of antihypertensive drugs , use of diabetes medications , use of cholesterol - lowering agents , sbp / dbp during follow - up in baseline analysis , or baseline sbp / dbp in follow - up analysis . since the interactions between sex and blood pressure and chd risk were not statistically significant among both whites and african americans , data for men and women were combined in the analyses . to avoid the potential bias due to severe diseases at baseline , additional analyses were carried out excluding the subjects who were diagnosed chd during the first 2 years of follow - up . we used restricted cubic splines in cox models to test whether there is a dose - response or nonlinear association of blood pressure as a continuous variable with cvd risk because a j- or u - shaped association of blood pressure with cvd risk has been found in prospective studies and rcts ( 11,12,22 ) . all statistical analyses were performed with pasw for windows , version 20.0 ( ibm spss , chicago , il ) . the patient s characteristics , including age of diabetes diagnosis , sex , race / ethnicity , family income , smoking status , types of insurance , body weight , height , bmi , blood pressure , total cholesterol , hdl cholesterol , ldl cholesterol , triglycerides , hba1c , estimated glomerular filtration rate ( egfr ) , and medication ( antihypertensive drug , cholesterol - lowing drug and antidiabetes drug ) , within a half year after the diabetes diagnosis ( baseline ) and during follow - up after the diabetes diagnosis ( follow - up ) were extracted from the computerized hospitalization records . blood pressure was measured from the right arm of the participant after 5 min of sitting using a mercury sphygmomanometer or electronic blood pressure meter in each visit ( 19 ) . an updated mean value of blood pressure over time was calculated for each individual from diabetes diagnosis to the final clinical measure of follow - up or to the last value before the occurrence of chd . the average number of blood pressure measurements during the follow - up period was 14.6 times . follow - up information was obtained from the lsuhls inpatient and outpatient database by using the unique number assigned to every patient who visits the lsuhcsd hospitals each time . the diagnosis of chd was the primary end point of interest of the study and was defined according to the icd-9 : chd ( icd-9 codes 410414 ) . since 1997 , diagnoses of chd were made by the treating physicians based on a clinical assessment and examinations as considered relevant by the clinician in charge of treatments . follow - up of each cohort member continued until the date of the diagnosis of chd , the date of the last visit if the subject stopped use of lsuhcsd hospitals , death , or 31 may 2012 ( 18 ) . the association between blood pressure and the risk of chd was analyzed by using cox proportional hazards models . systolic blood pressure ( sbp ) and diastolic blood pressure ( dbp ) were evaluated in the following two ways 1 ) as six categories ( sbp < 110 , 110119 , 120129 , 130139 [ reference group ] , 140159 , and 160 mmhg ; dbp < 65 , 6569 , 7079 , 8089 [ reference group ] , 90100 , and 100 mmhg ; and sbp / dbp < 110/65 , 110119/6569 , 120129/7079 , 130139/8089 [ reference group ] , 140159/9099 , and 160/100 mmhg ) , and 2 ) as a continuous variable ( sbp and dbp ) . different levels of blood pressure were included in the models as dummy and categorical variables , and the significance of the trend over different categories of blood pressure was tested in the same models by giving an ordinal numeric value for each dummy variable . all analyses were adjusted for age and sex and further for smoking , income , types of insurance , hba1c , ldl cholesterol , egfr , use of antihypertensive drugs , use of diabetes medications , use of cholesterol - lowering agents , sbp / dbp during follow - up in baseline analysis , or baseline sbp / dbp in follow - up analysis . since the interactions between sex and blood pressure and chd risk were not statistically significant among both whites and african americans , data for men and women were combined in the analyses . to avoid the potential bias due to severe diseases at baseline , additional analyses were carried out excluding the subjects who were diagnosed chd during the first 2 years of follow - up . we used restricted cubic splines in cox models to test whether there is a dose - response or nonlinear association of blood pressure as a continuous variable with cvd risk because a j- or u - shaped association of blood pressure with cvd risk has been found in prospective studies and rcts ( 11,12,22 ) . all statistical analyses were performed with pasw for windows , version 20.0 ( ibm spss , chicago , il ) . general characteristics of the study population are presented by race in supplementary table 1 . during a mean follow - up period of 6.0 years the age- and sex - adjusted hazard ratios ( hrs ) for incident chd at different levels of sbp at baseline ( < 110 , 110119 , 120129 , 130139 [ reference group ] , 140159 , and 160 mmhg ) were 1.27 ( 95% ci 1.071.51 ) , 1.10 ( 0.951.27 ) , 1.03 ( 0.911.16 ) , 1.00 , 1.05 ( 0.951.16 ) , and 1.12 ( 1.011.24 ) ( p trend = 0.058 ) for african american diabetic patients and 1.57 ( 1.351.82 ) , 1.14 ( 1.001.30 ) , 1.05 ( 0.931.18 ) , 1.00 , 0.98 ( 0.891.08 ) , and 1.03 ( 0.931.15 ) ( p trend<0.001 ) for white diabetic patients , respectively ( table 1 ) . a significantly increased risk of chd was observed among both african american and white diabetic patients with sbp < 120 mmhg and a borderline significantly increased risk with sbp 160 mmhg . after further adjustment for other confounding factors ( smoking , income , type of insurance , bmi , a1c , ldl cholesterol , egfr , use of antihypertensive drugs , use of diabetes medications , and use of cholesterol - lowering agents ) , this u - shaped association did not change among white ( p trend < 0.001 ) or african american ( p trend = 0.057 ) diabetic patients . the multivariable - adjusted hrs of chd associated with dbp at baseline ( < 65 , 6569 , 7080 , 8090 [ reference group ] , 90100 , and 100 mmhg ) were 1.25 , 1.07 , 0.96 , 1.00 , 1.03 , and 1.12 ( p trend < 0.001 ) for african american diabetic patients and 1.38 , 1.29 , 1.03 , 1.00 , 0.97 , and 1.13 ( p trend < 0.001 ) for white diabetic patients , respectively ( table 1 ) . when sbp or dbp was considered as a continuous variable by using restricted cubic splines , a nadir of the u - shaped association of blood pressure with chd risk hr ( 95% ci ) of chd according to different levels of sbp and dbp at baseline and during follow - up among african american and white patients with diabetes the multivariable - adjusted hrs of chd associated with different levels of joint sbp / dbp at baseline ( < 110/65 , 110119/6569 , 120129/7080 , 130139/8090 [ reference group ] , 140159/90100 , and 160/100 mmhg ) were 1.73 , 1.16 , 1.04 , 1.00 , 1.06 , and 1.11 ( p trend < 0.001 ) for african american diabetic patients and 1.60 , 1.27 , 1.08 , 1.00 , 0.95 , and 0.99 ( p trend < 0.001 ) for white diabetic patients , respectively ( table 2 ) . after further adjustment for sbp / dbp during follow - up in baseline analysis or baseline sbp / dbp blood pressure in follow - up analysis , this u - shaped association did not change ( tables 1 and 2 ) . hr ( 95% ci ) of chd according to different levels of sbp / dbp at baseline and during follow - up among african american and white patients with diabetes the u - shaped association of blood pressure with chd risk was confirmed among african american and white diabetic patients with or without antihypertensive drugs ( all p trend < 0.01 ) ( table 3 ) . after exclusion of the subjects who were diagnosed with chd during the first 2 years of follow - up ( n = 589 ) , the multivariable - adjusted hrs for different levels of blood pressure did not change ( data not shown ) . hr ( 95% ci ) of chd according to different levels of blood pressure at baseline and during follow - up among diabetic patients using ( n = 25,061 ) and not using ( n = 5,093 ) antihypertensive drugs there was a significant interaction between age and blood pressure on chd risk ( table 4 ) . when stratified by age , the u - shaped association of blood pressure at baseline with chd was present in diabetic patients aged 3049 and 5059 years ; however , this u shape changed to an inverse association in diabetic patients aged 60 years . hr ( 95% ci ) of chd according to different levels of blood pressure at baseline and during follow - up among diabetic patients stratified by age when we did an additional analysis by using an updated mean of blood pressure , we found almost the same u - shaped associations between baseline blood pressure levels and an updated mean of blood pressure levels with chd risk among both african american and white diabetic patients ( table 14 ) . our study found a u - shaped association between blood pressure at baseline and during follow - up with the risk of chd among both african american and white diabetic patients . in addition , we found that this u - shaped association was present in different age - groups , especially among diabetic patients aged < 50 years . for the oldest group ( age 60 years ) , the u - shaped association changed to an inverse association . the benefits of treating hypertension in diabetes patients are well documented in several early rcts ( 8,9 ) . however , there is a lack of supporting evidence for an aggressive blood pressure goal ( < 130/80 mmhg ) ( 57 ) . one recent analysis from the action to control cardiovascular risk in diabetes ( accord ) study did not confirm the beneficial effect of intensive blood pressure treatment ( sbp < 120 mmhg ) among diabetic patients compared with standard therapy ( sbp < 140 mmhg ) ( 11 ) . the international verapamil sr - trandolapril ( invest ) study also indicated that tight control of sbp ( < 130 mmhg ) among diabetic patients was not associated with improved cvd outcomes compared with usual control ( sbp 130139 mmhg ) ( 11,12 ) . the limitations of these rcts include the low incident chd events , short follow - up time , high loss to follow - up rates , and strict inclusion and exclusion criteria that limit their applicability to diabetic patients in clinical practice . it has been indicated that observational studies and rcts overall produced similar results ( 23,24 ) , and observational studies , especially from hospital - based cohorts , may reflect everyday clinical practice . observational study has indicated a u - shaped association of sbp or dbp with all - cause mortality among type 2 diabetic patients ( 22 ) . other studies have demonstrated an inverse association between blood pressure levels and all - cause mortality among elderly diabetic patients ( 14,25 ) . first , small sample sizes , short follow - up , and few cvd cases in some studies may limit the statistical power . second , most epidemiological studies only assess a single baseline measurement of blood pressure with the cvd risk , which may produce potential bias . in the current study , our data showed that a significantly increased risk of chd was observed among both african american and white diabetic patients in the high blood pressure group and the low blood pressure group as well . this u - shaped association of cvd risk was confirmed by blood pressure at baseline or during follow - up , which may suggest that a single blood pressure determination was sufficient where addition of subsequent values did not change the result very much . in addition , this u - shaped association was present in different age - groups , but in the oldest group ( age 60 years ) the u - shaped association changed to an inverse association . some studies have suggested that tight control of blood pressure might increase cardiovascular risk by the underperfusion of vital organs ( 26 ) . an impaired coronary circulation may be particularly sensitive to decreases in dbp ( 27,28 ) . avoidance of reducing dbp below a critical level is especially important to ensure coronary flow during diastole . lower blood pressure has been shown to be more common with comorbidities at older ages and is often reflective of poor health . elderly patients with type 2 diabetes represent a population that is highly enriched with underlying coronary artery disease and may be more prone than others to display the u - shaped or inversed association . this may contribute to the inverse association between blood pressure and chd risk in the old diabetic patients . we carried out sensitivity analyses excluding participants who were diagnosed with chd during the first 2 years of follow - up ( n = 589 ) , which can reduce the possibility of potential bias due to poor health during the subclinical stage prior to the diagnosis of chd . the association of lower blood pressure control ( < 120/70 mmhg ) with the increased chd risk in the elder group did not change ; on the other hand , the harm of uncontrolled blood pressure ( 160/100 mmhg ) seemed to decrease compared with other two younger groups . this might suggest that lower blood pressure control is more harmful than uncontrolled blood pressure and that an inverse association exists in elderly patients . the possible explanations why the inverse relationship was only found for elderly patients are unclear , but a recent analysis of 13 cohort studies including 180,000 japanese participants showed that the effect of hypertension on the risk of mortality gradually weakened with advancing age ( 29 ) . there are several strengths of our study , including the large sample size , high proportion of african americans , long follow - up time , and use of administrative databases to avoid differential recall bias . we have used both baseline blood pressure levels and updated mean values of blood pressure during follow - up in the analyses , which can avoid potential bias from a single baseline measurement . in addition , participants in this study use the same public health care system , which minimizes the influence from the accessibility of health care , particularly in comparing african americans and whites . one limitation of our study is that our analysis was not performed on a representative sample of the population , which limits the generalizability of this study ; however , lsuhcsd hospitals are public hospitals and cover > 1.6 million patients , most of whom are middle- or low - income persons in louisiana . the results of the current study will have wide applicability for the population with low income and without health insurance in the u.s . second , the validity of myocardial infarction diagnoses in our study has not been confirmed by specialists . but the method we used is hospital discharge register to diagnose major nonfatal chd , which has been widely used in american and european cohort studies , such as the kaiser permanente medical care program ( 30,31 ) , the atherosclerosis risk in communities ( aric ) study ( 32 ) , the framingham study ( 33,34 ) , the national finrisk survey ( 35 ) , and the whitehall ii study ( 36 ) . the validity of the diagnoses of myocardial infarction by using hospital discharge register in these cohort studies is available ( agreement 8398% ) ( 31,37 ) . third , even though our analyses adjusted for an extensive set of confounding factors , residual confounding due to the measurement error in the assessment of confounding factors and unmeasured factors such as heart rate , physical activity , education , dietary factors , cognitive function for all patients can not be excluded . based on the limitation above , our findings may need to be further confirmed by rcts or meta - analysis concerning this specific issue . in summary , in this large hospital - based cohort study , we found that aggressive blood pressure control ( i.e. , sbp < 120 mmhg or dbp < 70 mmhg ) is associated with an increased risk of chd among both african american and white diabetic patients with type 2 diabetes . since there is currently no robust evidence available for lowering the blood pressure < 130/80 mmhg in people with diabetes , it might be advisable to maintain blood pressure between 130139 and 8089 mmhg and to recommend less intense goals to elderly patients than to younger ones .
objectiveblood pressure control can reduce the risk of coronary heart disease ( chd ) among diabetic patients ; however , it is not known whether the lowest risk of chd is among diabetic patients with the lowest blood pressure level.research design and methodswe performed a prospective cohort study ( 20002009 ) on diabetic patients including 17,536 african americans and 12,618 whites . 
 cox proportional hazards regression models were used to estimate the association of blood pressure with chd risk.resultsduring a mean follow - up of 6.0 years , 7,260 chd incident cases were identified . 
 the multivariable - adjusted hazard ratios of chd associated with different levels of systolic / diastolic blood pressure at baseline ( < 110/65 , 110119/6569 , 120129/7080 , and 130139/8090 mmhg [ reference group ] ; 140159/90100 ; and 160/100 mmhg ) were 1.73 , 1.16 , 1.04 , 1.00 , 1.06 , and 1.11 ( p trend < 0.001 ) , respectively , for african american diabetic patients , and 1.60 , 1.27 , 1.08 , 1.00 , 0.95 , and 0.99 ( p trend<0.001 ) for white diabetic patients , respectively . 
 a u - shaped association of isolated systolic and diastolic blood pressure at baseline as well as blood pressure during follow - up with chd risk was observed among both african american and white diabetic patients ( all ptrend < 0.001 ) . 
 the u - shaped association was present in the younger age - group ( 3049 years ) , and this u - shaped association changed to an inverse association in the older age - group ( 60 years).conclusionsour study suggests that there is a u - shaped or inverse association between blood pressure and the risk of chd , and aggressive blood pressure control ( blood pressure < 120/70 mmhg ) is associated with an increased risk of chd among both african american and white patients with diabetes .