Effect of Vitamin D on Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: In nonhypertensive individuals, lower levels of 25-hydroxyvitamin D (25[OH]D) have been associated with an increased risk of hypertension, and vitamin D deficiency has been associated with endothelial dysfunction in such individuals. However, the effect of vitamin D supplementation on endothelial dysfunction in nonhypertensive individuals has not been examined in a rigorous fashion.

Methods: In this randomized, double-blind, placebo-controlled trial of nonhypertensive, nondiabetic overweight, or obese individuals with vitamin D deficiency (body mass index ≥25 and 25[OH]D ≤ 20 ng/ml), we assigned subjects to receive either ergocalciferol (50,000 units) or matching placebo, once a week for 8 weeks.

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.

Maximum renal responses to renin inhibition in healthy study participants: VTP-27999 versus aliskiren.

Background: Renin inhibition with aliskiren induced the largest increases in renal plasma flow (RPF) in salt-depleted healthy volunteers of all renin-angiotensin system (RAS) blockers. However, given its side-effects at doses higher than 300 mg, no maximum effect of renin inhibition could be established. We hypothesized that VTP-27999, a novel renin inhibitor without major side-effects at high doses, would allow us to establish this.

Impaired cerebrovascular hemodynamics are associated with cerebral white matter damage.

White matter hyperintensities (WMH) in elderly individuals with vascular diseases are presumed to be due to ischemic small vessel diseases; however, their etiology is unknown. We examined the cross-sectional relationship between cerebrovascular hemodynamics and white matter structural integrity in elderly individuals with vascular risk factors. White matter hyperintensity volumes, fractional anisotropy (FA), and mean diffusivity (MD) were obtained from MRI in 48 subjects (75±7years).

Neurovascular coupling, cerebral white matter integrity, and response to cocoa in older people.

Objective: To investigate the relationship between neurovascular coupling and cognitive function in elderly individuals with vascular risk factors and to determine whether neurovascular coupling could be modified by cocoa consumption.

Methods: Sixty older people (aged 72.9 ± 5.

Habitual flavonoid intake and endothelial function in healthy humans.

Objective: Endothelial function, as measured by noninvasive techniques, is known to vary widely within populations. Our study was designed to test the hypothesis that this variation is determined in large part by a person's habitual dietary intake of flavonoids.

Methods: This was an analytical study examining the relationship between endothelial function and dietary flavonoids in 19 healthy older adults (mean age 72 years).

Renal responses to three types of renin-angiotensin system blockers in patients with diabetes mellitus on a high-salt diet: a need for higher doses in diabetic patients?

Objective: Activation of the renal renin-angiotensin system in patients with diabetes mellitus appears to contribute to the risk of nephropathy. Recently, it has been recognized than an elevation of prorenin in plasma also provides a strong indication of risk of nephropathy. This study was designed to examine renin-angiotensin system control mechanisms in the patient with diabetes mellitus.

Renin inhibitors.

KEY POINTS AND PRACTICAL RECOMMENDATIONS: •  Aliskiren, the sole oral renin inhibitor approved by the US Food and Drug Administration, is indicated for the treatment of hypertension, either as monotherapy or in combination, with reductions in blood pressure similar to other agents. •  Early evidence suggests that aliskiren confers additional benefit in patients with diabetic nephropathy. Data are not yet available to determine whether protection will extend to cardiovascular disease.

Brief intervention for women with risky drinking and medical diagnoses: a randomized controlled trial.

This is a randomized controlled trial of 511 eligible women treated for diabetes, hypertension, infertility, or osteoporosis on an outpatient basis to test the hypothesis that those randomized to a brief intervention (BI) will drink less than those in the control condition 12 months later. A secondary goal was to identify the characteristics associated with changes in drinking outcome. All 511 completed the initial alcohol assessment, and 96% completed the 12-month follow-up interview.

Identification of risk drinking women: T-ACE screening tool or the medical record.

Background: Risk drinking for women is defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) as >7 drinks per week or >3 drinks per occasion. This study compares the T-ACE screening tool and the medical record for identification of risk drinking by 611 women receiving outpatient treatment for diabetes, hypertension, infertility, or osteoporosis in Boston, Massachusetts, between February 2005 and May 2009.

Methods: All subjects completed a diagnostic interview about their health habits, and medical records were abstracted.

Brain blood flow and velocity: correlations between magnetic resonance imaging and transcranial Doppler sonography.

Objective: Because transcranial Doppler sonography (TCD) is unable to measure arterial diameter, it remains unproven whether the changes in cerebral blood velocity it measures are representative of changes in cerebral blood flow (CBF). Our study was designed to compare velocity changes with flow changes measured by two magnetic resonance imaging (MRI) techniques, perfusion MRI and arterial spin labeling (ASL), using flavanol-rich cocoa to induce CBF changes in healthy volunteers.

Methods: We enrolled 20 healthy volunteers aged 62 to 80 years (mean, 73 years).

Renal plasma flow: glomerular filtration rate relationships in man during direct renin inhibition with aliskiren.

We examined the relation between change in renal plasma flow (RPF) and change in glomerular filtration rate (GFR) in healthy humans on a low-salt diet during direct renin inhibition with aliskiren. We measured the renal hemodynamic response to acute dosing of 300mg aliskiren by mouth to 19 healthy normotensive subjects (age, 33+/-3 years; baseline RPF, 575+/-23; GFR, 138+/-14mL/min/1.73m(2)) on a low-sodium diet (10mmol/day).

Flavanols, the Kuna, cocoa consumption, and nitric oxide.

The Kuna Indians, who reside in an archipelago on the Caribbean Coast of Panama, have very low blood pressure (BP) levels, live longer than other Panamanians, and have a reduced frequency of myocardial infarction, stroke, diabetes mellitus, and cancer-at least on their death certificates. One outstanding feature of their diet includes a very high intake of flavanol-rich cocoa. Flavonoids in cocoa activate nitric oxide synthesis in healthy humans.

Plasma 25-hydroxyvitamin D and regulation of the renin-angiotensin system in humans.

Vitamin D regulates the renin-angiotensin system (RAS) in experimental animals, but corresponding human data are limited. We examined the relation between plasma 25-hydroxyvitamin D and elements of the RAS in 184 normotensive individuals in high sodium balance; these included circulating levels of plasma renin activity and angiotensin II (Ang II) and the renal plasma flow response to infused Ang II, which is an indirect measure of the intrinsic RAS activity in the kidney. Compared with individuals with sufficient 25-hydroxyvitamin D levels (> or = 30.

Physical activity and albuminuria.

Higher urinary albumin excretion predicts future cardiovascular disease, hypertension, and chronic kidney disease. Physical activity improves endothelial function so activity may reduce albuminuria. Among diabetics, physical activity decreases albuminuria.

Post-menopausal hormone use and albuminuria.

Background: Higher levels of urinary albumin excretion predict future hypertension and chronic kidney disease. Post-menopausal hormone use may influence the renin-angiotensin system and renal endothelial function, impacting albumin excretion. The association between post-menopausal hormone use and albuminuria is not well defined.

Genetic polymorphisms and the risk of accelerated renal function decline in women.

Background: Reduced glomerular filtration rate is an important predictor of cardiovascular disease and death. Genetic polymorphisms, particularly in genes involved in the renin-angiotensin system (RAS), may influence the rate of renal function decline.

Methodology/principal Findings: We examined the relation between specific single nucleotide polymorphisms (SNPs), including those in the RAS, apolipoprotein E and alpha-adducin, and renal function decline assessed by estimated glomerular filtration rate (eGFR) over an 11-year period in 2578 Caucasian participants of the Nurses' Health Study.

Vitamin D-mediated hypercalcemia and Cushing syndrome as manifestations of malignant pleural mesothelioma.

Objective: To report a case of coincident hypercalcemia and Cushing syndrome arising from mesothelioma.

Methods: We describe the clinical, laboratory, imaging, and pathologic findings of a patient with malignant pleural mesothelioma and elucidate the underlying biologic mechanisms resulting in concurrent overexpression of steroid and polypeptide hormones.

Results: A 62-year-old woman presented with chest discomfort and cough.

Aliskiren accumulates in Renin secretory granules and binds plasma prorenin.

The vascular effects of aliskiren last longer than expected based on its half life, and this renin inhibitor has been reported to cause a greater renin rise than other renin-angiotensin system blockers. To investigate whether aliskiren accumulation in secretory granules contributes to these phenomena, renin-synthesizing mast cells were incubated with aliskiren, washed, and exposed to forskolin in medium without aliskiren (0.1 to 1000 nmol/L).

Cerebral blood flow response to flavanol-rich cocoa in healthy elderly humans.

Background And Purpose: Cerebral ischemia is a common, morbid condition accompanied by cognitive decline. Recent reports on the vascular health benefits of flavanol-containing foods signify a promising approach to the treatment of cerebral ischemia. Our study was designed to investigate the effects of flavanol-rich cocoa (FRC) consumption on cerebral blood flow in older healthy volunteers.

Higher levels of albuminuria within the normal range predict incident hypertension.

Higher levels of albumin excretion within the normal range are associated with cardiovascular disease in high-risk individuals. Whether incremental increases in urinary albumin excretion, even within the normal range, are associated with the development of hypertension in low-risk individuals is unknown. This study included 1065 postmenopausal women from the first Nurses' Health Study and 1114 premenopausal women from the second Nurses' Health Study who had an albumin/creatinine ratio <25 mg/g and who did not have diabetes or hypertension.

Renal and hormonal responses to direct renin inhibition with aliskiren in healthy humans.

Background: Pharmacological interruption of the renin-angiotensin system focuses on optimization of blockade. As a measure of intrarenal renin activity, we have examined renal plasma flow (RPF) responses in a standardized protocol. Compared with responses with angiotensin-converting enzyme inhibition (rise in RPF approximately 95 mL x min(-1) x 1.

Angiotensinogen genotype predicts abnormal renal hemodynamics in young hypertensive patients.

Objective: In essential hypertensive patients, blunted renal plasma flow responsiveness to angiotensin II suggests a pathologic increase in angiotensin II in the kidneys. This blunting has been associated with the angiotensinogen 235TT genotype. As several measures of renal function decline with age, we sought to determine the interaction of age and genotype on this intermediate phenotype.

Renin-angiotensin system polymorphisms and risk of hypertension: influence of environmental factors.

Renin-angiotensin system (RAS) polymorphisms have been studied as candidate risk factors for hypertension with inconsistent results, possibly due to heterogeneity among various environmental factors. We analyzed the association between RAS candidate gene polymorphisms and risk of hypertension among 2722 women and also explored whether these associations varied according to menopausal status, body mass index, and dietary factors. In a main-effects analysis of all 2722 women adjusted for age and race, homozygosity for the AT1R A1166C polymorphism was associated with hypertension (odds ratio, 1.