Ala92 type 2 deiodinase allele increases risk for the development of hypertension.

Accumulating evidence suggests that genes of the hypothalamic-pituitary-thyroid pathway influence susceptibility to hypertension. Type 2 iodothyronine deiodinase is responsible for the conversion of thyroxine to tri-iodothyronine for use in peripheral tissues. The present study evaluated whether a type 2 iodothyronine deiodinase nonsynonymous polymorphism, threonine 92 to alanine (Thr92Ala), is a determinant of hypertension susceptibility. A total of 372 euthyroid subjects were genotyped for Thr92Ala polymorphism using the Sequenom MassARRAY platform. Associations with hypertension and hypertension-related intermediate phenotypes were performed with generalized estimating equations. Type 2 iodothyronine deiodinase Thr92Ala allele frequencies differed significantly between hypertensive and normotensive subjects, with an excess of Ala92 carriers in hypertensive compared with normotensive subjects (64.8% versus 47.1%; P=0.011). Adjusted for age, gender and race, the estimated odds ratio for hypertension in Ala92 allele carriers compared with Thr92 homozygotes was 2.11 (95% CI: 1.15 to 3.89). Among euthyroid adults, the common Ala92 allele of the type 2 iodothyronine deiodinase increases risk for the development of hypertension. These data support an important role for genetic variation in the hypothalamic-pituitary-thyroid pathway in influencing susceptibility to hypertension.

Uric acid and the development of hypertension: the normative aging study.

Experimental evidence supports a causative role for uric acid in the pathogenesis of hypertension. Prospective studies have variably adjusted for relevant confounders and have been of relatively limited duration. We prospectively examined the relationship between uric acid level and the development of hypertension in the Normative Aging Study, a longitudinal cohort of healthy adult men. Of the 2280 initial men in the Normative Aging Study, 2062 had available information for inclusion in the analysis. Cox proportional hazards model was used to examine the relationship between baseline serum uric acid level and the development of hypertension adjusting for age, body mass index, abdominal circumference, smoking, alcohol, plasma triglycerides, total cholesterol, and plasma glucose. A total of 892 men developed hypertension over a mean of 21.5 years of follow-up. Serum uric acid level independently predicted the development of hypertension in age-adjusted (relative risk [RR]: 1.10; 95% CI: 1.06 to 1.15: P<0.001) and multivariable (RR: 1.05; 95% CI: 1.01 to 1.10; P=0.02) models. Among 1277 men at risk for the development of hypertension at the time of their first serum creatinine measurement, 508 (39.8%) developed hypertension over a mean of 10.3+/-5.5 years of follow-up. Additionally adjusting for calculated glomerular filtration rate in this subset, serum uric acid remained associated with the development of hypertension (RR: 1.06; 95% CI: 1.01 to 1.12; P=0.03). The baseline serum uric acid level is a durable marker of risk for the development of hypertension. The association is independent of elements of the metabolic syndrome, alcohol intake, and renal function.

Aggregation of high-normal thyroid-stimulating hormone in hypertensive families.

BACKGROUND: Studies suggest that there are genetic variants that influence both blood pressure regulation and serum TSH levels. We investigated whether high-normal TSH values aggregate in hypertensive families. The influence of hypertension family history on serum TSH levels in healthy normotensive individuals was also examined. METHODS: All subjects were euthyroid (TSH, 0.5-5.0 mIU/liter). The study subjects were 333 hypertensives, including 229 members of multiple sibling families. The subjects had blood samples for serum TSH determination drawn in the morning after overnight bed rest. High-normal TSH was defined as values above 2.0 mIU/liter and equal to or less than 5.0 mIU/liter. Thirty-one healthy normotensives provided information about their family history of hypertension by telephone. RESULTS: The concordance for high-normal TSH values among hypertensive, multiple sibling families was greater than expected by chance (P = 0.009). There were nearly twice as many families concordant for high-normal TSH status as expected (13.2% vs. 7.0%), whereas the observed proportion concordant for normal TSH status was similar to that expected (58.3% vs. 54.1%). Family membership explained a significant proportion of variance in TSH status (P = 0.038). Healthy normotensives with a family history of hypertension had significantly higher TSH values (2.2 +/- 1.2 mIU/liter) than those with a negative family history of hypertension (TSH 1.3 +/- 0.7 mIU/liter) independent of other characteristics (P = 0.025). CONCLUSIONS: There is familial aggregation of high-normal TSH values in hypertensive families, and a hypertension family history influences serum TSH levels in healthy individuals. These findings are consistent with the existence of genetic variants affecting both blood pressure regulation and serum TSH levels.

Diabetes self-management among low-income Spanish-speaking patients: a pilot study.

BACKGROUND: The prevalence of type 2 diabetes and diabetes-related morbidity and mortality is higher among low-income Hispanics when compared to that of Whites. However, little is known about how to effectively promote self-management in this population. PURPOSE: The objectives were first to determine the feasibility of conducting a randomized clinical trial of an innovative self-management intervention to improve metabolic control in low-income Spanish-speaking individuals with type 2 diabetes and second to obtain preliminary data of possible intervention effects. METHODS: Participants for this pilot study were recruited from a community health center, an elder program, and a community-wide database developed by the community health center, in collaboration with other agencies serving the community, by surveying households in the entire community. Participants were randomly assigned to an intervention (n = 15) or a control (n = 10) condition. Assessments were conducted at baseline and at 3 months and 6 months postrandomization. The intervention consisted of 10 group sessions that targeted diabetes knowledge, attitudes, and self-management skills through culturally specific and literacy-sensitive strategies. The intervention used a cognitive-behavioral theoretical framework. RESULTS: Recruitment rates at the community health center, elder program, and community registry were 48%, 69%, and 8%, respectively. Completion rates for baseline, 3-month, and 6-month assessments were 100%, 92%, and 92%, respectively. Each intervention participant attended an average of 7.8 out of 10 sessions, and as a group the participants showed high adherence to intervention activities (93% turned in daily logs, and 80% self-monitored glucose levels at least daily). There was an overall Group x Time interaction (p = .02) indicating group differences in glycosylated hemoglobin over time. The estimated glycosylated hemoglobin decrease at 3 months for the intervention group was -0.8% (95% confidence intervals = -1.1%, -0.5%) compared with the change in the control group (p = .02). At 6 months, the decrease in the intervention group remained significant, -0.85% (95% confidence intervals = -1.2, -0.5), and the decrease was still significantly different from that of the controls (p = .005). There was a trend toward increased physical activity in the intervention group as compared to that of the control group (p = .11) and some evidence (nonsignificant) of an increase in blood glucose self-monitoring in the intervention participants but not the control participants. Adjusting for baseline depressive scores, we observed a significant difference in depressive symptoms between intervention participants and control participants at the 3-month assessment (p = .02). CONCLUSIONS: Low-income Spanish-speaking Hispanics are receptive to participate in diabetes-related research. This study shows that the pilot-tested diabetes self-management program is promising and warrants the conduct of a randomized clinical trial.

Uric acid and the state of the intrarenal renin-angiotensin system in humans.

BACKGROUND: Experimental hyperuricemia is marked by an activated intrarenal renin-angiotensin system (RAS). The renal vascular response to exogenous angiotensin II (Ang II) provides an indirect measure of intrarenal RAS activity. We tested the hypothesis that the serum uric acid concentration predicts the renal vascular response to Ang II. METHODS: A total of 249 subjects in high sodium balance had the renal plasma flow (RPF) response to Ang II measured. Para-aminohippuric acid (PAH) clearance was used to estimate RPF. Multivariable regression analysis determined if the serum uric acid concentration independently predicts the RPF response to Ang II. Variables considered included age, gender, race, body mass index (BMI), hypertension status, blood pressure, basal RPF, creatinine clearance, serum insulin, serum glucose, serum high-density lipoprotein (HDL), serum triglycerides, and plasma renin activity (PRA). RESULTS: Uric acid concentration negatively correlated with the RPF response to Ang II (r=-0.37, P < 0.001). In univariate analysis, age, BMI, hypertension, triglycerides, and blood pressure were negatively associated, and basal RPF, HDL, and female gender were positively associated with the RPF response to Ang II. In multivariable analysis, serum uric acid concentration independently predicted the RPF response to Ang II (beta=-5.3, P < 0.001). CONCLUSION: Serum uric acid independently predicted blunted renal vascular responsiveness to Ang II, consistent with results from experimental hyperuricemia showing an activated intrarenal RAS. This could be due to a direct effect of uric acid or reflect a more fundamental renal process. These data may have relevance to the association of uric acid with risk for hypertension and nephropathy.

Mineralocorticoid receptor antagonists and hypertension: is there a rationale?

Accumulating evidence indicates that aldosterone is involved in cardiovascular disease by inducing inflammation in the presence of moderate amounts of salt in the diet. Spironolactone and eplerenone are the mineralocorticoid receptor (MR) antagonists currently available for the treatment of hypertension. They have similar safety and antihypertensive efficacy. The advantage of eplerenone is the lower incidence of anti-androgenic and progestational side effects. The rationale for using MR blockade in the treatment of hypertension is threefold: the evidence of antihypertensive efficacy, the phenomenon of "aldosterone escape" occurring with angiotensin-converting enzyme inhibitor and angiotensin-receptor blockade therapy, and the compelling evidence that MR antagonism reduces target-organ damage in hypertensive patients and improves survival in patients with cardiovascular disease. Thus, blockade of the MR may be very useful in many patients with hypertension, particularly those at risk for or having evidence of target-organ damage.

Thyroid function and blood pressure homeostasis in euthyroid subjects.

Overt and subclinical hypothyroidism are associated with increased systemic vascular resistance and hypertension. We examined the relationship between thyroid function and blood pressure homeostasis in euthyroid individuals. A total of 284 subjects (68% hypertensive) consumed high- (200 mmol) and low- (10 mmol) sodium diets, and their blood pressure responses were assessed as percentage change in the mean arterial pressure (MAP). p-Aminohippuric acid clearance was used to estimate effective renal plasma flow. Renal vascular resistance (RVR) was calculated as MAP divided by effective renal plasma flow. Serum free T(4) index (FTI) was lower (P < 0.0001) and TSH was higher (P = 0.046) in hypertensive compared with normotensive subjects independent of other baseline characteristics. FTI (beta = -1.51, P < 0.0001), baseline MAP, and race independently predicted MAP salt sensitivity. The FTI relationship with salt sensitivity adjusted for baseline MAP and race was similar among normotensive (beta = -1.42, P = 0.008) and hypertensive subjects (beta = -1.66, P = 0.0001). FTI correlated negatively with high- (P = 0.0001) and low- (P = 0.008) salt RVR, whereas TSH correlated positively with high- (P = 0.016) and low- (P = 0.012) salt RVR independent of age, gender, race, and body mass index. We have found that FTI is lower and TSH is higher in hypertensive compared with normotensive euthyroid subjects and that FTI independently predicts blood pressure salt sensitivity. These data show that the influence of thyroid function on blood pressure homeostasis extends into euthyroid range and likely reflects the action of thyroid hormone on peripheral vasculature.