WNK1 kinase polymorphism and blood pressure response to a thiazide diuretic

Single nucleotide polymorphisms (SNPs) in genes encoding or influencing renal sodium transport systems were investigated as potential predictors of blood pressure (BP) response to a thiazide diuretic. A sample of 585 adults with essential hypertension (30 to 59.9 years of age; 50% blacks; 47% women) were treated with hydrochlorothiazide for 4 weeks (25 mg daily, orally) to determine office BP responses. Ambulatory BP responses were measured in a subset of 228 subjects. After adjustment for ethnicity, sex, age, and waist-to-hip ratio, 3 SNPs in WNK1 (rs2107614, rs2277869, and rs1159744), encoding a lysine-deficient protein kinase that regulates thiazide-sensitive sodium-potassium cotransport, made statistically significant contributions to predicting ambulatory BP responses, accounting for 2% to 4% of variation in systolic and diastolic responses (P<0.05). SNPs in the beta2-adrenoceptor (rs2400707) and the epithelial sodium channel gamma-subunit (rs5723 and rs5729) were associated with similar magnitude of variation in ambulatory systolic BP response (P=0.028) or office diastolic BP response (P<0.05), respectively. However, SNPs evaluated in the furosemide-sensitive sodium-potassium chloride cotransporter, potassium inwardly rectifying channel, chloride channel, thiazide-sensitive sodium chloride cotransporter, epithelial sodium channel beta-subunit, and the mineralocorticoid receptor were not associated with significant variation in ambulatory or office BP responses. Polymorphisms in genes regulating renal sodium transport, in particular WNK1, predict interindividual differences in antihypertensive responses to hydrochlorothiazide.     

Insulin and blood pressure during weight loss in obese adolescents

The role of insulin in the regulation of blood pressure was evaluated in 50 obese adolescents before and after a 20-week weight loss program. When compared with 10 nonobese adolescents, the obese subjects had significantly higher systolic, diastolic, and mean arterial pressures (p = 0.005), an elevated 24-hour urinary sodium excretion (p = 0.002), an elevated fasting insulin concentration (p = 0.001), and an abnormal insulin response to an oral glucose tolerance test (sum of the insulins at 0, 1, and 2 hours post-oral glucose load; p = 0.001). We also observed a significant correlation between systolic and diastolic blood pressure (age and sex normalized) and body weight (r = 0.57, p less than 0.01 and r = 0.7, p less than 0.01), fasting insulin (r = 0.49, p less than 0.01 and r = 0.54, p less than 0.01), and sum of insulins (r = 0.42, p less than 0.01 and r = 0.46, p less than 0.01). To study the effect of weight loss on the relationship between blood pressure and insulin, the obese subjects were randomly assigned to three groups: 15 to a diet and behavior change group, 18 to a diet, behavior change, and exercise group, and 17 to an obese control group. Compared with the obese control group, the two weight loss groups each experienced a significant decrease in insulin (p less than 0.01), sum of the insulins (p less than 0.01), and blood pressure (p less than 0.01). The decrease in blood pressure during the weight loss program significantly correlated with the change in both insulin and body weight.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of weight loss on blood pressure and drug consumption in normal weight patients

The effect of weight loss on blood pressure and on antihypertensive drug consumption was examined in 81 nonobese subjects with essential hypertension who had been chronically treated with antihypertensive drugs. A hypocaloric diet was prescribed for 5 months. A weight loss greater than 2 kg in 5 months was considered significant. Quality and quantity of antihypertensive medications were scored according to a formula. In the subjects whose medication and weight did not change, mean arterial pressure remained unchanged, whereas it decreased significantly (-7.1 +/- 1.9 mm Hg) in those who showed significant weight loss (-3.28 +/- 0.34 kg) with no change in medication. Among the subjects whose antihypertensive medication remained constant during the diet program there was a significant correlation between the change in weight and mean arterial pressure (r = 0.45, p less than 0.01). Mean arterial pressure increased significantly (+5.1 +/- 1.7 mm Hg) in subjects whose weight remained unchanged with a decrease in medication, whereas it remained significantly lower than the control (by -3.1 +/- 2.0 mm Hg) in those whose weight decreased significantly (-4.57 +/- 0.69 kg) with the decrease in medication. The weight loss-induced decrease in blood pressure occurred independently of the initial degree of obesity and the initial level of mean arterial pressure. Urinary sodium excretion in the control period and at the end of the diet program did not differ significantly between subgroups. These results indicate that, even in subjects of normal weight with essential hypertension, weight loss can induce a fall in blood pressure that leads to a reduction of antihypertensive medication.(ABSTRACT TRUNCATED AT 250 WORDS)     

Circadian variation and blood pressure: response to rapid weight loss by hypocaloric hyponatraemic diet in obesity.

Ambulatory intra-arterial blood pressure was monitored in 15 obese hypertensive and 10 obese normotensive subjects weighing more than 30% of their ideal body weight. Measurements were taken before and after 1 month in hospital on a diet of 330kCal/day designed to ensure 34 g protein and 65 mmol sodium. Mean +/- s.d. body mass index in the whole group fell from 40.8 +/- 7.6 to 37.2 +/- 7.4 kg/m2 (P less than 0.0001). Daytime intra-arterial blood pressure fell from 176 +/- 19/102 +/- 14 to 162 +/- 16/95 +/- 14 mmHg (P less than 0.0005 and P less than 0.002) in the hypertensive group and from 141 +/- 15/82 +/- 5 to 131 +/- 13/79 +/- 4 mmHg (P less than 0.005 for systolic pressure) in the normotensive group. Circadian variation of systolic intra-arterial blood pressure comparing the mean daytime with the mean night-time blood pressure recordings showed a day-night difference of 27 +/- 10 mmHg in the normotensive group compared with 12 +/- 13 mmHg in the hypertensive group (P less than 0.01). This trend was reversed after weight loss, when the normotensive group showed a day-night difference of 20 +/- 13 mmHg compared with 18 +/- 17 mmHg in the hypertensive group. Thus, circadian variation of systolic intra-arterial blood pressure in the hypertensive group was significantly (P less than 0.01) reduced compared with the normotensive group prior to, but not after, weight loss. These data show that, in obese subjects, weight loss produced a significant reduction in ambulatory intra-arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of weight loss on clinic and ambulatory blood pressure in normotensive men

Obesity and physical inactivity are associated with both elevated cardiovascular risk and blood pressure (BP), but the interrelation of exercise, weight loss and BP is poorly understood. This study examines the independent effects of exercise and weight loss on both standard clinic and automated, ambulatory BP in 115 overweight, sedentary, normotensive men (aged 30 to 59 years) who were randomly assigned to control status or to lose weight over 1 year by moderate caloric restriction (dieting) or by increased caloric expenditure (exercise). Median daytime and evening BP were determined from measurements made every 20 minutes while the subjects were awake. After 1 year, the control group gained (mean +/- standard deviation) 0.5 +/- 3.8 kg while the diet group lost 6.9 +/- 4.4 kg and the exercise group lost 4.6 +/- 3.5 kg. Clinic BP decreased similarly in all 3 groups, but daytime and evening ambulatory BP decreased in both intervention groups and increased in the control group. Relative to the 1-year change in control subjects, net change in daytime ambulatory BP averaged -2 to -3 mm Hg in both dieters and exercisers, while net change in evening ambulatory BP averaged -3 to -4 mm Hg. These changes were all statistically significant (p less than 0.05) when compared with control subjects except for daytime systolic BP in both intervention groups and evening diastolic BP in dieters. Weight loss achieved through caloric restriction or expenditure may cause important decreases in BP in normotensive men; exercise appears to confer no unique benefit. If confirmed, these results have important public health implications for the prevention of cardiovascular disease.     

Reactivity to norepinephrine and effect of sodium on blood pressure during weight loss

Eighteen moderately obese middle-aged men with untreated mild hypertension were randomized to two groups and placed on a low energy diet regimen for 9 to 11 weeks. In Group I (n = 10) the amount of sodium chloride in the diet maintained the urinary sodium excretion at the predieting level. Mean body mass was reduced by 9.1 +/- 0.7 (SEM) kg. Mean intra-arterial pressure showed no significant change. There were significant decreases in heart rate (p less than 0.05) and urinary norepinephrine excretion (p less than 0.05) but not in plasma concentration of norepinephrine. In Group II (n = 8) energy as well as sodium intake was restricted, with a 95 +/- 22 mmol/24 hour reduction of urinary sodium excretion. Body mass decreased by 9.3 +/- 1.1 kg, and mean arterial pressure decreased by -18.9 to -4.3 mm Hg (95% confidence interval). There were also significant reductions in heart rate (p less than 0.001) and plasma norepinephrine concentrations (p less than 0.01) but not in urinary norepinephrine excretion. The pressor response (mean arterial pressure) to norepinephrine infusion at different dose rates was significantly elevated (p less than 0.05) in Group I during dieting in comparison with baseline. The blood pressure response to norepinephrine during dieting in patients in Group II was not changed from baseline.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in blood pressure and body weight following smoking cessation in women

OBJECTIVE: Few have studied the long-term effects of smoking and smoking cessation on weight gain and blood pressure increase and compared with the age-related increases experienced by most adults. This study compared the development of weight and blood pressure in female never smokers, continuing smokers and smokers who quit smoking. DESIGN: Weight, systolic (SBP) and diastolic (DBP) blood pressure and smoking habits were assessed at baseline and re-assessed after a mean follow-up of 9.0 +/- 5.8 years. SETTING: Population-based cohort. SUBJECTS: A total of 2381 female never smokers and 1550 female smokers. At the re-examination, 388 of the smokers had quit smoking. RESULTS: Mean weight gain was 7.6 +/- 6.1, 3.2 +/- 5.8 and 3.7 +/- 5.2 kg, respectively, in quitters, continuing smokers and never smokers (P < 0.001). In women without blood pressure treatment, mean SBP increase was 20.9 +/- 16.8, 19.1 +/- 15.8 and 16.1 +/- 16.3 mmHg, respectively, in these groups (P < 0.001). Mean DBP increase was 6.2 +/- 8.7, 5.7 +/- 9.3 and 3.1 +/- 8.0 mmHg, respectively (P < 0.001). After adjustments for potential confounders, the increased weight gain in quitters remained highly significant. The differences in SBP and DBP increase were attenuated after adjustments, but remained significant. Incidence of hypertension (> or = 160/95 mmHg or treatment) was significantly higher in quitters [adjusted odds ratio (OR): 1.8; CI: 1.4-2.5] when compared with continuing smokers (OR: 1.3; CI: 1.07-1.6) and never smokers (reference). CONCLUSION: Over a long follow-up, weight gain was approximately 3-4 kg higher in quitters when compared with continuing smokers or never smokers. Although the differences in blood pressure increase were moderate, smoking cessation was associated with an increased incidence of hypertension.     

Association between blood pressure and insulin resistance in obese females during weight loss and weight rebound phenomenon.

The purpose of this study was to investigate the effect of weight loss on blood pressure and its related variables in moderately obese Japanese females, including an investigation of the rebound phenomenon. Study I examined the effects of weight loss on blood pressure in 138 moderately obese, nondiabetic females (BMI 29.3+/-0.3 kg/M2; age, 46.3+/-0.8 years) during a 3-month therapeutic dietary and exercise program. Study II investigated the effect of weight rebound on blood pressure over an additional 21 months of exercise in 48 subjects from Study I subjects. After 3 months, the BMI significantly decreased to 27.9+/-0.3 kg/m2. Abdominal total fat, visceral fat (V), and subcutaneous fat (S) also decreased significantly. In addition, the summation of insulin (sigmaIRI), plasma glucose (sigmaPG) and HOMA during 75 g oral glucose tolerance test also all significantly decreased. Significant decreases in both the SBP and DBP were observed after the 3 month weight reduction program. Multiple regression analysis revealed that the reduction in SBP was significantly and positively associated with the reduction in log sigmaIRI and the reduction in log 24h-urinary norepinephrine excretion at the end of Study I. The DBP showed a significantly positive association with the log sigmaIRI. With regard to the weight rebound phenomenon, Study II showed that the SBP, DBP and sigmaIRI all increased significantly, and a positive correlation was observed between the changes in the SBP and those in the log sigmaIRI. However, no such correlation was observed regarding the abdominal total fat and visceral fat during both periods. These results suggest that weight loss therefore caused the BP to decrease due to both an improvement in hyperinsulinemia and a decrease in the adrenergic activity which may be involved in the urinary catecholamine. As a result, hyperinsulinemia is thus considered to play an important role in the pathogenesis of blood pressure due to obesity not only during weight loss, but also during the weight rebound phenomenon.     

Relationship between changes in serum leptin levels and blood pressure after weight loss.

Insulin resistance is thought to raise blood pressure. Recently, a significant positive relationship between mean blood pressure and plasma leptin levels, but there have been no reports dealing with the relationship between blood pressure and either insulin resistance or serum leptin levels after weight loss. In the present work, we attempted to clarify the relationship between changes in blood pressure and either the serum leptin level or the insulin level in 102 moderately obese females (mean body mass index (BMI), 29.5 +/- 0.5 kg/m2; age, 47.0 +/- 0.9) during a 3 month period. No differences in age, fat-mass, homeostasis model assessment (HOMA), the summation of insulin (sigmaIRI), plasma renin activity (PRA) or 24 h norepinephrine excretion (24hU-NE) were observed between the hypertensive (HT) group (n = 31) and normotensive (NT) group (n = 71) before weight loss, but the basal serum leptin was significantly higher in the HT (16.8 +/- 1.1 ng/ml) than in the NT group (15.2 +/- 0.8 ng/ml), after adjusting for abdominal total fat. After a 3 month weight reduction program, the total abdominal fat, serum leptin and sigmaIRI significantly decreased in both groups. The systolic blood pressure (SBP)/diastolic blood pressure (DBP) significantly decreased from 144/84 to 130/77 mmHg only in the HT but not in the NT group. The PRA decreased in both groups, while the 24hU-NE significantly decreased only in the HT group. The changes in the leptin level were significantly correlated with the changes in both sigmaIRI and HOMA after weight loss in the two groups, respectively. Finally, a statistically significant positive correlation was observed between the changes in the leptin and the changes in the mean blood pressure (MBP) (r = 0.412, p < 0.05) only in the HT group. Multiple regression analysis revealed that the changes in MBP were independently associated with the changes in 24hU-NE and the changes in either sigmaIRI or HOMA in all subjects. However, a statistically significant positive correlation was observed between the changes in MBP and the changes in leptin levels even after adjusting for the total abdominal fat, 24hU-NE and either sigmaIRI or HOMA (both expressed as a percentage of the baseline value) in a multiple regression analysis only in the HT group. These results suggest that leptin may play a role in the pathophysiology of obese hypertension.     

Patient- and physician-level determinants of blood pressure response to treatment in normal weight and overweight patients (the PREVIEW study)

Background and aimsObesity combined with hypertension places patients at greater risk for target-organ damage and cardiovascular disease. The purpose of this secondary analysis was to identify physician- and patient-levels determinants of blood pressure (BP) values and predictors of uncontrolled BP through subgroup analysis by body mass index (BMI).Methods and resultsWe conducted a subgroup analysis of 3006 patients with High-BMI (BMI >25 kg/m²; n = 2124) and Normal-BMI (BMI<25 kg/m²; n = 882) treated by 504 physicians and enrolled in PREVIEW, a Belgian prospective, multi-center, pharmaco-epidemiological study of 90-day second-line treatment with valsartan. Physician- and patient-level determinants of BP values and BP control were identified by means of hierarchical linear and logistic regression.Blood pressure values and control after 90 days of treatment were consistently lower for the High-BMI group. The 25.5% of variance in 90-day systolic and 28.3% of the variance in 90-day diastolic BP were attributable to physician-level determinants for the High-BMI group; versus 27.3% and 29.8% for the Normal-BMI group (ICC = 0.273 and 0.298, respectively). Determinants of 90-day BP values and predictors of uncontrolled BP varied considerably by BMI status.ConclusionSeveral common and unique patient- and physician-level determinants of BP values and control were identified for the High-BMI and Normal-BMI groups. These findings highlight the need for differentiating healthcare interventions to account for patient and physician variables, particularly with respect to effective BP management in vulnerable populations.     

Low birth weight and blood pressure

Evidence supporting the association of normal and pathologically elevated blood pressure with low birth weight is presented and discussed in this article because of the overwhelming global prevalence of hypertension and its impact on individuals and nations. The findings provide strong impetus for the medical and public health communities to consider the concept of the "developmental origins of health and disease" in developing approaches to address the growing burden of hypertension worldwide.     

Physical activity and weight loss following bariatric surgery

Physical activity is a cornerstone in the medical management of obesity and could be important for weight loss following bariatric surgery. This review aims to describe the evolution of physical activity following massive weight loss induced by bariatric surgery, and to identify the relationship between physical activity and amount of weight loss. A literature search identified 20 publications (19 studies) reporting physical activity data in relation to bariatric surgery. All studies were observational. Self‐assessment of physical activity was used in all the studies. Objective measures (pedometry) were used in two studies. The time frame for physical activity assessment varied: before surgery in two publications, after surgery in nine, and longitudinal pre‐ to post‐operative evolution in nine. The latter nine publications found an increase in physical activity after bariatric surgery. In 10/13 studies where it was described, there was a positive relationship between physical activity level and amount of weight loss. In conclusion, observational evidence of self‐reported physical activity suggests that physical activity increases after bariatric surgery and that physical activity is associated with surgically induced weight loss. However, these findings warrant further evaluation using objective measures of physical activity and testing in controlled trials.