Influence of leptin, adiponectin, and resistin on the association between abdominal adiposity and arterial stiffness.

BACKGROUND: Adiposity is associated with arterial stiffness, and both adiposity and arterial stiffness independently predict morbidity and mortality. Because adipocytes account for most adipokine production, the objectives of this study were to examine the influence of adipokines such as leptin, adiponectin, and resistin on the relationship between abdominal adiposity and arterial stiffness. METHODS: This is a cross-sectional analysis of data from the Baltimore Longitudinal Study of Aging (BLSA). Adiposity was measured as kilograms of abdominal adipose tissue using dual-energy X-ray absorptiometry (DXA). Arterial stiffness was assessed as carotid-femoral pulse wave velocity (PWV). Leptin, adiponectin, and resistin were assayed in fasting serum samples. The influence of adipokines on the relationship between adiposity and arterial stiffness by adipokines was examined using standard mediation pathway analysis. RESULTS: Among 749 participants ages 26-96 years (mean age 67, 52% men, 27% black), abdominal adiposity was positively associated with PWV (relative ratio (RR) = 1.04, P = 0.02), after adjusting for potential confounders but was attenuated and no longer significant after adjusting for leptin (RR = 0.99, P = 0.77). The relationship between adiposity and PWV was not substantially influenced by adiponectin (RR = 1.03, P = 0.06) or resistin (RR = 1.05, P = 0.010). Leptin (RR = 1.02, P < 0.001), resistin (RR = 0.92, P < 0.0001), and adiponectin (RR = 0.97, P = 0.004), but not abdominal adiposity (RR = 1.00, P = 0.94), retained significant associations with PWV when adjusting for each other and confounders. CONCLUSIONS: Our findings are consistent with the hypothesis that leptin explains, in part, the observed relationship between abdominal adiposity and arterial stiffness. Adiponectin, leptin, and resistin are independent correlates of PWV.

Effect of Beta-blocker therapy on rehospitalization rates in women versus men with heart failure and preserved ejection fraction.

Beta blockers are empirically used in many patients with heart failure (HF) and preserved ejection fraction (HFpEF) because they allow more time for diastolic filling and because they improve outcomes in patients with systolic HF. However, recent data suggest that impaired chronotropic and vasodilator responses to exercise, which can worsen with beta blockade, may play a key role in the pathophysiology of HFpEF. We prospectively examined the association between beta-blocker therapy after hospitalization for decompensated HF and HF rehospitalization at 6 months in 66 consecutive patients with HFpEF (71 +/- 13 years old, 68% women, 42% Black). Subjects were stratified based on receiving (BB+; 15 men, 28 women) or not receiving (BB-) beta-blockers at hospital discharge. In men, HF rehospitalization occurred less frequently in the BB+ than in the BB- group, albeit nonsignificantly (20% vs 50%, p = 0.29). In women, HF rehospitalization occurred more frequently in the BB+ than in the BB- group (75% vs 18%, p <0.001). In univariate analyses, discharge beta-blocker was associated with HF rehospitalization in women (odds ratio [OR] 14.00, 95% confidence interval [CI] 3.09 to 63.51, p = 0.001), but not in men (OR 0.25, 95% CI 0.03 to 1.92, p = 0.18). In a forward logistic regression model that offered all univariate predictors of HF rehospitalization, discharge beta blocker remained an independent predictor of HF rehospitalization in women (OR 11.06, 95% CI 1.98 to 61.67, p = 0.006). In conclusion, this small observational study suggests that beta-blocker therapy may be associated with a higher risk of HF rehospitalization in women with HFpEF. The risks and benefits of beta-blocker therapy in patients with HFpEF should be evaluated in randomized, controlled trials.

Is longitudinal pulse pressure a better predictor of 24-hour urinary albumin excretion than other indices of blood pressure?

The strong relationship between urinary albumin excretion (UAE) and pulse pressure (PP) in cross-sectional studies suggests that pressure pulsatility may contribute to renal microvascular injury. The longitudinal relationships between UAE and the various indices of blood pressure (BP) are not well studied. We compared the associations of UAE with the longitudinal exposure to PP and systolic, diastolic, and mean BPs. UAE was measured from 24-hour urine collections in 450 community-dwelling subjects (age: 57+/-15 years, 53% women, all with UAE <200 microg/min). For each subject, longitudinal indices of BP were estimated by dividing the area under the curve of serial measurements of BP (median: 5) during 1 to 22 years preceding UAE measurement by the number of follow-up years. Median (interquartile range) UAE was 4.7 microg/min (3.3 to 7.8 microg/min) in women and 5.2 microg/min (3.7 to 9.8 microg/min) in men. In women, UAE was not related to longitudinal indices of BP. In men, in multivariable-adjusted models that included either longitudinal systolic and diastolic BPs or longitudinal PP and mean BP, UAE was independently associated with systolic (standardized regression coefficient [beta]=0.227; P=0.03) but not with diastolic (beta=-0.049; P=0.59) BP and with PP (beta=0.216; P=0.01) but not with mean BP (beta=0.032; P=0.72). Comparisons of these 2 models and stepwise regression analyses both indicated that, of the 4 longitudinal indices of BP, PP was the strongest predictor of UAE in men. The pulsatile component of BP confers the highest risk for BP-induced renal microvascular injury. Future studies should examine whether PP reduction provides additional renoprotection beyond that attained by conventional BP goals alone.

Do hypertensive individuals have enlarged aortic root diameters? Insights from studying the various subtypes of hypertension.

BACKGROUND: Aortic root diameter (AoD) increases with aging and is related to body size. AoD is also presumed to increase in hypertension. In prior studies, however, after adjusting for age and body size, AoD did not differ between hypertensive and normotensive (NT) individuals. Hypertension is a heterogeneous condition with various subtypes that differ in pathophysiology and age distribution. We assessed whether AoD differs among subjects with the various subtypes of hypertension and nonhypertensive individuals. METHODS: In 1,256 volunteers aged 30-79 years (48% women, 48% hypertensive; all untreated), AoD was measured at the sinuses of Valsalva with transthoracic echocardiography. Using cutoff values based on the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, subjects were identified as NT (23%), or prehypertensive (PH, 29%), or as having isolated diastolic (IDH, 6%), isolated systolic (ISH, 12%), or systolic-diastolic (SDH, 30%) hypertension. Groups were compared using analysis of variance with Bonferroni's correction. RESULTS: AoD increased with age and body surface area (BSA) in both men (r = 0.25 and 0.19, respectively) and women (r = 0.30 and 0.22, respectively) (all P < 0.0001). In men, those identified as having IDH, ISH, and SDH each had a 6% larger AoD than NT individuals (all P < 0.05). In women, those identified with ISH and SDH had a 10 and 8% larger AoD than NT individuals, respectively (all P < 0.05). In both sexes, after indexing to BSA, only ISH individuals exhibited larger AoD compared with NT individuals (both P < 0.05). But, with further adjustment for age, these differences were no longer observed. CONCLUSIONS: Even when the subtypes of hypertension are examined separately, age and BSA, not hypertension status, account for the AoD differences between NT and hypertensive subjects.

Pulse pressure is inversely related to aortic root diameter implications for the pathogenesis of systolic hypertension.

Hypertension accelerates the age-associated increase in aortic root diameter (AoD), likely because of chronically elevated distending pressures. However, the pulsatile component of blood pressure may have a different relationship with AoD. We sought to assess the relationship between AoD and pulse pressure (PP) while accounting for left ventricular and central arterial structural and functional properties, which are known to influence PP. The study population was composed of 1256 individuals, aged 30 to 79 years (48% women and 48% hypertensive), none of whom were on antihypertensive medications. Blood pressure was measured in the sitting position with conventional sphygmomanometry. PP was calculated as the difference between systolic and diastolic blood pressures. AoD was measured at end diastole at the level of the sinuses of Valsalva with echocardiography. The relationship between AoD and PP was evaluated with multiple regression analyses. PP was 50+/-14 mm Hg in men and 54+/-18 mm Hg in women, and AoD was 31.9+/-3.5 mm in men and 28.9+/-3.5 mm in women. After adjusting for age, age(2), height, weight, and mean arterial pressure, AoD was independently and inversely associated with PP in both sexes. After further adjustments for central arterial stiffness and wall thickness, reflected waves, and left ventricular geometry, AoD remained inversely associated with PP in both men (coefficient=-0.48; P=0.0003; model R(2)=0.51) and women (coefficient=-0.40; P=0.01; model R(2)=0.61). Thus, AoD is inversely associated with PP, suggesting that a small AoD may contribute to the pathogenesis of systolic hypertension. Longitudinal studies are needed to examine this possibility.