overweight and obesity are associated with elevated blood pressure , and high percentage of hypertensive patients are overweight and obese . subjects gaining weight are at higher risk for hypertension [ 2 , 3 ] , whereas the weight reduction decreases blood pressure levels as well as the complications related to hypertension . obesity has also been recognized as an independent risk factor for arterial hypertension , and , in particular , the framingham heart study showed that approximately 65% to 75% of overweight and obese patients are at risk for hypertension . examining 3216 outpatient subjects who were never treated with antihypertensive medication , kotsis et al . showed that confirmed ambulatory blood pressure hypertension was found to be higher in both overweight and obese individuals compared with normal weight subjects . as far as fat distribution is concerned , visceral fat has the most important impact on blood pressure elevation .   concerning the mechanism relating obesity to hypertension , most obese humans have increased sympathetic activity , and some authors have shown that sympathetic activation is higher in subjects with central than with peripheral phenotype of obesity [ 10 , 11 ] . moreover , most obese patients have hyperinsulinemia , and it is well known that insulin stimulates sympathetic activity   and that this effect occurs even when the insulin levels are included within the physiological range . the renin - angiotensin - aldosterone system ( ras ) has also been identified as an additional abnormality that can explain the association between obesity and hypertension [ 1315 ] . lastly , it has been shown that blood pressure and obesity covariation are mediated by circulating high levels of leptin , suggesting that the body fat has only a weak independent effect on blood pressure variation after adjustment for leptin levels . it has been also shown that hyperinsulinemia is determinant for unfavourable metabolic aspects of metabolic syndrome , whereas catecholamines seem to be important for the development of impaired glucose metabolism and hypertension .   a recent study performed in a cohort of overweight and obese patients , never treated by antihypertensive treatment , showed that obesity is associated to the tendency to higher systolic blood pressure and lower diastolic blood pressure , at least before that hypertension becomes stable , corresponding to profound alterations in artery structural and functional characteristics . the same study has shown that daily noradrenaline production contributes to higher 24  h mean systolic blood pressure levels . these results seem to suggest that obesity per se is associated to higher pulse pressure , that is , the difference between systolic and diastolic blood pressure . interestingly , ft3 serum levels are higher in women with abdominal obesity and are independently associated with waist circumference . noteworthy , systolic blood pressure is typically elevated , and diastolic pressure is often low in patients of thyrotoxicosis , which results in a higher pulse pressure , and these findings are attributable to increased cardiac output , stroke volume , heart rate , and cardiac contractility and a marked fall in systemic vascular resistance . therefore , it may well be that patients with abdominal obesity having higher ft3 serum levels have also higher pulse pressure . however , at the best of our knowledge , no study has investigated a possible significant relationship between free thyroid hormones and blood pressure levels in obesity . in particular , we examined whether tsh , ft3 , and ft4 serum levels may predict 24  h   mean systolic and diastolic blood pressure levels and pulse pressure in a cohort of 231 euthyroid overweight and obese patients , aged 1868 yrs , who had never received antihypertensive medication , independently of other parameters . the patients were consecutively enrolled at the outpatient clinic for the study of hypertension , department of internal medicine and clinical oncology , university of bari , school of medicine . concerning the inclusion criteria , all of them were addressed to the outpatient clinic by their general practitioners because of a recent increase of their ambulatory blood pressure levels . to obtain the selected population for this study , patients with the following disorders were excluded : endocrinological diseases , diabetes mellitus , stroke , transient ischemic attack , angina pectoris , heart infarction , claudicatio intermittens , congenital heart disease , or ecg abnormalities . thus , the study enrolled 231 patients , including 103 women and 128 men , aged 1868 yrs . the trial protocol has been approved by an ethical committee and meets the standards of the declaration of helsinki in its revised version of 1975 and its amendments of 1983 , 1989 , and 1996 . all patients reported to have normal fasting blood glucose levels before enrolment into the study , but 7 had a fasting blood glucose  126  mg / dl , but lower than 140  mg / dl . all study subjects were judged in good health on the basis of physical examination , medical history , routine blood work , urinalysis , and electrocardiogram . none of patients were receiving any medication ( including oral contraceptives for premenopausal women and hormone replacement therapy for postmenopausal women ) since at least three months before the enrollment into the study . moreover , none of them had been involved into intensive or competitive physical activity prior to the enrollment . during the testing period , all subjects were asked to keep their normal mixed diet and not to perform any sporting activity . the day before the measurement , they were abstained from both caffeinated and alcoholic drinks but maintained their normal diet . bmi was calculated as the weight ( kg ) divided by the square of height ( m ) . waist circumference was measured at the narrowest part of the abdomen , that is , at the natural indentation between the 10th rib and the iliac crest ( minimum waist ) . outpatient clinic blood pressure was recorded on at least three different occasions , using a mercury manometer with an appropriate cuff size . ambulatory blood pressure was measured with 15-minute intervals from 07:00 to 23:00 and with 30-minute intervals from 23:00 to 07:00 for consecutive 24  h , starting from 08:30 ( ultralite abpm monitor 90217 , spacelabs media inc , redmond , wa ) . all abpm measurements were valid , meaning that < 30% of the measurements were missing , data were lacking for an interval of < 2  h , and the nighttime sleep period was never < 6  h or > 12  h. according to the 2007 esh - esc practice guidelines for the management of arterial hypertension , hypertension was confirmed when 24  h mean systolic blood pressure was 125  mmhg and/or 24  h mean diastolic blood pressure was 80  mmhg . pulse pressure was formally defined as the daily mean systolic pressure minus the daily mean diastolic pressure . blood samples were drawn between 08:00  h and 09:00  h after an overnight fast , within one week from the day of the ambulatory blood pressure measurement . serum insulin concentrations were measured by radioimmunoassay ( behring , scoppitto , italy ) , and intra- and interassay coefficients of variation were 3.7% and 7.5% , respectively . plasma glucose levels were determined by the glucose - oxidase method ( sclavo , siena , italy ) , and plasma lipids ( triglycerides , total cholesterol , and hdl cholesterol ) were measured by an automatic colorimetric method ( hitachi ; boehringer mannheim , mannheim , germany ) . significant relationships between 24  h mean sbp , 24  h mean dbp , and 24  h mean pp and all other parameters were evaluated by pearson 's correlation coefficient . a multiple regression analysis was performed to test the joint effect of different variables on 24  h mean sbp or 24  h mean dbp or 24  h mean pp . , tulsa , oklahoma ) , and the statistical analyses were made using statistica 6.1 software ( statsoft inc . table 1 shows general and anthropometric parameters , abpm data , and metabolic and hormone variables in overweight and obese subjects under study . table 2 shows the relationship between 24  h mean systolic ( sbp ) and 24  h mean diastolic blood pressure ( dbp ) with all other parameters . sbp showed a direct significant association only with waist circumference and ft3 levels , whereas dbp showed a significant relationship only with age ( positive ) and bmi ( negative ) . table 3 shows the results of a linear multivariate analysis , with 24  h sbp considered as the dependent variable and ft3 levels , male sex , and age as independent parameters ( adjusted r = 0.054 , p < 0.001 ) . ft3 levels , male sex , and age showed an independent significant association with 24  h sbp ; however , when waist circumference was also entered into the analysis ( adjusted r = 0.071 , p < 0.001 ) , only age and waist circumference maintained an independent association with 24  h systolic blood pressure ( table 4 ) . table 5 shows the relationship between 24  h pulse pressure ( pp ) with all other parameters . 24  h pp showed a significant positive association with bmi , waist circumference , insulin and ft3 levels . table 6 shows the results of a linear multivariate analysis , with 24  h pp considered as the dependent variable and male sex , age , and insulin and ft3 levels as independent parameters ( adjusted r = 0.137 , p < 0.001 ) . only ft3 levels and waist circumference maintained an independent significant association with 24  h pp . again , when homair was introduced in the multivariate analysis in substitution of insulin , only ft3 levels and waist circumference maintained an independent significant association with 24  h pp ( data not shown ) . at the best of our knowledge , this is the first study examining the relationship between free thyroid hormones and 24  h mean blood pressure levels in euthyroid overweight and obese subjects , who had never received antihypertensive medication . on the basis of a direct independent relationship between daily mean pulse pressure and waist circumference , this study shows that abdominal obesity is characterized by higher pulse pressure , at least before artery remodeling and hypertension stabilization , thus confirming the results of a recent study performed by our group . the strongest novel finding of this study was the direct relationship between ft3 levels and pulse pressure , independently of age , sex , insulin levels , and homair . these results support the hypothesis that higher ft3 circulating levels per se may be responsible for an increase in systolic blood pressure and a decrease of diastolic blood pressure in subjects with abdominal obesity . the relationship between insulin levels ( or homair ) and pulse pressure was not maintained when ft3 levels were introduced in the multiple regression analysis , thus apparently excluding that insulin or insulin resistance has a significant role in the association between pulse pressure and abdominal obesity or between pulse pressure and ft3 levels . we found also a direct relationship between ft3 levels and daily mean sbp , independently of age and sex . all these results are in line with the effects of t3 on systolic and diastolic blood pressure . in fact , t3 is well known to increase the effect of catecholamines on cardiac output , stroke volume , heart rate , and cardiac contractility . moreover , napoli et al . have shown that t3 directly enhances endothelium - dependent vasodilation on resistance vessels . in addition , thyroid hormones have been shown to have direct vasodilatory effects on vascular muscle cells , endothelial dysfunction may be more prevalent in hypothyroid patients [ 26 , 27 ] , and increased diastolic blood pressure and higher arterial stiffening are present in subclinical hypothyroid patients . since ft3 serum levels have been shown to be higher in obese women with higher waist circumference , the effects of higher ft3 concentrations on the heart and on resistance vessels may contribute to the relationship between waist circumference and pulse pressure in our overweight and obese patients . it is to note that the positive association between ft3 levels and daily mean sbp was not maintained when data were adjusted for waist circumference in multiple regression analysis , suggesting that the increase of ft3 levels and the possible influence of higher ft3 levels on systolic in obese subjects are just secondary to central fat accumulation .   in conclusion , the present study , performed in overweight and obese subjects , either normotensive or with recently discovered hypertension , shows that ft3 circulating levels are positively associated with pulse pressure , independently of age , sex , insulin levels , and insulin resistance . these results support the hypothesis that higher ft3 circulating levels per se may be responsible for an increase in systolic blood pressure and a decrease of diastolic blood pressure in subjects with abdominal obesity .
objective . 
 this study examined whether obesity is characterized by higher 24  h mean pulse pressure ( 24  h mean sbp-24  h mean dbp ) and whether free thyroid hormones ( ft3 and ft4 ) have a relationship with 24  h mean pulse pressure . 
 methods . 
 a total of 231 euthyroid overweight and obese patients , 103 women and 128 men , aged 1868  yrs , normotensive ( n = 69 ) or with recently developed hypertension ( n = 162 ) , never treated with antihypertensive drugs , were investigated . 
 fasting insulin , tsh , ft3 , ft4 , glucose , and lipid serum concentrations were measured . 
 waist circumference was measured as an indirect parameter of central fat accumulation . 
 ambulatory blood pressure monitoring ( abpm ) was performed . 
 results . 
 24  h mean pulse pressure ( pp ) showed a significant positive correlation with bmi ( p < 0.001 ) , waist circumference ( p < 0.001 ) , and ft3 ( p 
 < 0.001 ) and insulin serum levels ( p < 0.05 ) . 
 when a multivariate analysis was performed , and 24  h pp was considered as the dependent variable , and waist circumference , ft3 , insulin , male sex , and age as independent parameters , 24  h mean pp maintained a significant association only with waist circumference ( p < 0.001 ) and ft3 levels ( p < 0.05 ) . 
 conclusion . 
 our results suggest that ft3 per se may contribute to higher pulse pressure in obese subjects .