Hypertension
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Higher arterial stiffness is associated with increased risk of atherosclerotic events. However, its contribution toward risk of heart failure (HF) and its subtypes, HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF), independent of other risk factors is not well established. In this study, we included Health ABC study (Health, Aging, and Body Composition) participants without prevalent HF who had arterial stiffness measured as carotid-femoral pulse wave velocity (cf-PWV) at baseline (n=2290). ⋯ In adjusted analysis, higher cf-PWV was associated with greater risk of HF after adjustment for age, sex, ethnicity, mean arterial pressure, and heart rate (hazard ratio [95% confidence interval] for cf-PWV tertile 3 versus tertile 1 [ref] =1.35 [1.05-1.73]). However, this association was not significant after additional adjustment for other cardiovascular risk factors (hazard ratio [95% confidence interval], 1.14 [0.88-1.47]). cf-PWV velocity was also not associated with risk of HFpEF and HFrEF after adjustment for potential confounders (most adjusted hazard ratio [95% confidence interval] for cf-PWV tertile 3 versus tertile 1 [ref]: HFpEF, 1.06 [0.72-1.56]; HFrEF, 1.28 [0.83-1.97]). In conclusion, arterial stiffness, as measured by cf-PWV, is not independently associated with risk of HF or its subtypes after adjustment for traditional cardiovascular risk factors.
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Randomized Controlled Trial
Effect of Uric Acid-Lowering Agents on Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Trial.
Higher levels of serum uric acid are independently associated with endothelial dysfunction, a mechanism for incident hypertension. Overweight/obese individuals are more prone to endothelial dysfunction than their lean counterparts. However, the effect of lowering serum uric acid on endothelial dysfunction in these individuals has not been examined thoroughly. ⋯ None of the interventions produced any significant change in endothelium-dependent vasodilation (probenecid, 7.4±5.1% at baseline and 8.3±5.1% at 8 weeks; allopurinol, 7.6±6.0% at baseline and 6.2±4.8% at 8 weeks; and placebo, 6.5±3.8% at baseline and 7.1±4.9% at 8 weeks). In this randomized, double-blind, placebo-controlled trial, uric acid lowering did not affect endothelial function in overweight or obese nonhypertensive individuals. These data do not support the hypothesis that uric acid is causally related to endothelial dysfunction, a potential mechanism for development of hypertension.
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A high-fructose diet is shown to induce salt-sensitive hypertension, but the underlying mechanism largely remains unknown. The major goal of the present study was to test the role of renal (pro)renin receptor (PRR) in this model. In Sprague-Dawley rats, high-fructose intake increased renal expression of full-length PRR, which were attenuated by allopurinol. ⋯ Radiotelemetry demonstrated that high-fructose or a high-salt diet alone did not affect mean arterial pressure, but the combination of the 2 maneuvers induced a ≈10-mm Hg increase of mean arterial pressure, which was blunted by PRO20 or allopurinol treatment. In cultured human kidney 2 cells, both fructose and uric acid increased protein expression of soluble PRR in a time- and dose-dependent manner; fructose-induced PRR upregulation was inhibited by allopurinol. Taken together, our data suggest that fructose via uric acid stimulates renal expression of PRR/soluble PRR that stimulate sodium/hydrogen exchanger 3 and Na/K/2Cl cotransporter expression and intrarenal renin-angiotensin system to induce salt-sensitive hypertension.
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Although microvascular disease is a hallmark of systemic sclerosis (SSc), a higher prevalence of macrovascular disease and a poorer related prognosis have been reported in SSc than in the general population. The simultaneous assessment of prognostically relevant functional properties of larger and smaller arteries, and their effects on central hemodynamics, has never been performed in SSc using the state-of-the-art techniques. Thirty-four women with SSc (aged 61±15 years, disease duration 17±12 years, and blood pressure 123/70±18/11 mm Hg) and 34 healthy women individually matched by age and mean arterial pressure underwent the determination of carotid-femoral (aortic) and carotid-radial (upper limb) pulse wave velocity (a direct measure of arterial stiffness), aortic augmentation (a measure of the contribution of reflected wave to central pulse pressure), and aortobrachial pulse pressure amplification (brachial/aortic pulse pressure) through applanation tonometry (SphygmoCor). ⋯ Age and mean arterial pressure were the only predictors of AIx@75. Women with SSc have increased aortic augmentation and decreased pulse pressure amplification (both measures of the contribution of reflected wave to central waveform) but no changes in aortic or upper limb arterial stiffness. Microvascular involvement occurs earlier than large artery stiffening in SSc.
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Masked hypertension is associated with increased risk for cardiovascular disease. Identifying modifiable risk factors for masked hypertension could provide approaches to reduce its prevalence. Life's Simple 7 is a measure of cardiovascular health developed by the American Heart Association that includes body mass index, physical activity, diet, cigarette smoking, blood pressure (BP), cholesterol, and glucose. ⋯ The multivariable-adjusted prevalence ratios for masked daytime hypertension comparing participants with 2, 3, and ≥4 versus ≤1 ideal Life's Simple 7 factors were 0.99 (95% confidence interval [CI], 0.74-1.33), 0.77 (95% CI, 0.57-1.03), and 0.51 (95% CI, 0.33-0.79), respectively. Masked daytime hypertension was less common among participants with ideal versus poor levels of physical activity (ratio, 0.74; 95% CI, 0.56-1.00), ideal or intermediate levels pooled together versus poor diet (prevalence ratio, 0.73; 95% CI, 0.58-0.91), ideal versus poor levels of cigarette smoking (prevalence ratio, 0.61; 95% CI, 0.46-0.82), and ideal versus intermediate levels of clinic BP (prevalence ratio, 0.28, 95% CI, 0.16-0.48). Better cardiovascular health is associated with a lower preva lence of masked hypertension.