Statin Use and 25-Hydroxyvitamin D Blood Level Response to Vitamin D Treatment of Older Adults.

OBJECTIVES: To determine whether statin use alters response of 25-hydroxyvitamin D (25(OH)D) level to vitamin D treatment. DESIGN: Pooled analysis. SETTING: Three double-blind randomized controlled trials that tested different doses of vitamin D. PARTICIPANTS: Participants of three trials (N = 646; mean age 76.3 ± 8.4, 65% female). MEASUREMENTS: In all three trials, 25(OH)D status and statin use were assessed repeatedly over time (baseline, 6 and 12 months). Repeated-measures analysis was used to compare 25(OH)D response to vitamin D treatment at baseline and 6 and 12 months of statin users and nonusers, controlling for age, sex, body mass index, Charlson Comorbidity Index, vitamin D dose, trial, and season. RESULTS: At baseline, 17.5% were statin users, and 65% were vitamin D deficient (25(OH)D < 20 ng/mL). Baseline 25(OH)D levels did not differ significantly between groups at baseline (18.8 for statin users, 17.2 ng/mL for nonusers, P = .07), but according to the longitudinal analyses, the total increase over 12 months in 25(OH)D concentration was significantly lower in statin users (13.1 ng/L) than nonusers (15.9 ng/mL; 21.4% difference; P = .009). CONCLUSION: Of persons aged 60 and older at high risk of vitamin D deficiency, statin users had a 21.4% smaller increase in 25(OH)D serum concentrations over time than nonusers, independent of vitamin D dose and other covariates.

Vascular Effects of Eplerenone in Coronary Artery Disease With Preserved Ejection Fraction: A Double-Blind, Randomized, Placebo-Controlled Trial.

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) reduce morbidity and mortality in heart failure with reduced ejection fraction (HFrEF). Their role in patients without heart failure, particularly in patients with coronary artery disease (CAD) and preserved EF, is still a matter of debate. HYPOTHESIS: The MRA eplerenone on top of standard medical therapy improves endothelial dysfunction and other markers of vascular health in CAD patients with preserved EF. METHODS: In this double-blind, randomized, placebo-controlled study, 42 patients (mean age: 63.5 ± 9.1 years; 37 males) were randomized to 4-week treatment with eplerenone 25 mg daily or placebo. The primary endpoint was difference in endothelial function as assessed by flow-mediated dilatation (FMD) of the brachial artery. Secondary endpoints included 24-hour blood pressure (BP), endothelial progenitor cells, and platelet adhesion. RESULTS: No difference in the primary endpoint FMD was noted after 4 weeks of treatment with eplerenone compared with placebo (FMD: 4.7% ± 2.0% and 4.9% ± 2.1%, respectively; P = 0.77). There were no significant differences between eplerenone and placebo in 24-hour BP (mean systolic BP: 126.9 ± 17.3 and 123.3 ± 9.7 mm Hg, P = 0.41; diastolic BP: 73.3 ± 12.9 and 72.0 ± 7.5 mm Hg, respectively, P = 0.69), number of endothelial progenitor cells, and platelet adhesion. CONCLUSIONS: Adding low-dose eplerenone to standard medical therapy did not improve important markers of vascular health in patients with CAD and preserved EF. Our results may help understand conflicting evidence from larger clinical trials on MRAs in patients with preserved EF.

Antihypertensive combination therapy in primary care offices: results of a cross-sectional survey in Switzerland.

BACKGROUND: Most hypertensive patients need more than one substance to reach their target blood pressure (BP). Several clinical studies indicate the high efficacy of antihypertensive combinations, and recent guidelines recommend them in some situations even as initial therapies. In general practice they seem widespread, but only limited data are available on their effectiveness under the conditions of everyday life. The objectives of this survey among Swiss primary care physicians treating hypertensive patients were: to know the frequency of application of different treatment modalities (monotherapies, free individual combinations, single-pill combinations); to see whether there are relationships between prescribed treatment modalities and patient characteristics, especially age, treatment duration, and comorbidities; and to determine the response rate (percentage of patients reaching target BP) of different treatment modalities under the conditions of daily practice. METHODS: This cross-sectional, observational survey among 228 randomly chosen Swiss primary care physicians analyzed data for 3,888 consecutive hypertensive patients collected at one single consultation. RESULTS: In this survey, 31.9% of patients received monotherapy, 41.2% two substances, 20.9% three substances, and 4.7% more than three substances. By combination mode, 34.9% took free individual combinations and 30.0% took fixed-dose single-pill combinations. Combinations were more frequently given to older patients with a long history of hypertension and/or comorbidities. In total, 67.8% of patients achieved their BP target according to their physician's judgment. When compared, single-pill combinations were associated with a higher percentage of patients achieving target BP than free individual combinations and monotherapies for the total sample and for patients with comorbidity. CONCLUSION: Antihypertensive combination therapy was widely used in Swiss primary care practices. The number of prescribed substances depended on age, treatment duration, and type and number of comorbidities. Although the response rate was generally modest under the conditions of daily practice, it was higher for single-pill combinations than for monotherapies and free individual combinations. Further studies are needed to confirm these observations.

Cocoa, blood pressure, and vascular function.

The consumption of a high amount of fruits and vegetables was found to be associated with a lower risk of coronary heart disease and stroke. Epidemiologically, a similar relationship has been found with cocoa, a naturally polyphenol-rich food. Obviously, double blind randomized studies are difficult to perform with cocoa and chocolate, respectively. However, intervention studies strongly suggest that cocoa has several beneficial effects on cardiovascular health, including the lowering of blood pressure, the improvement of vascular function and glucose metabolism, and the reduction of platelet aggregation and adhesion. Several potential mechanisms through which cocoa might exert its positive effects have been proposed, among them activation of nitric oxide synthase, increased bioavailability of nitric oxide as well as antioxidant, and anti-inflammatory properties. It is the aim of this review to summarize the findings of cocoa and chocolate on blood pressure and vascular function.

Nonsteroidal antiinflammatory drugs, acetaminophen, and hypertension.

Selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) as well as acetaminophen belong to the most widely prescribed therapeutic agents worldwide. Their efficacy in pain relief notwithstanding, the use of NSAIDs is associated with an increased cardiovascular risk, which can be partly attributed to their blood pressure raising potential. Adequately powered placebo-controlled trials specifically evaluating the cardiovascular safety of NSAIDs vs. selective COX inhibitors are currently underway. This review summarizes the current knowledge on the cardiovascular effects of NSAIDs and acetaminophen, and their potential clinical consequences.

Vascular abnormalities in essential hypertension.

Arterial hypertension is a very common disease and an important risk factor for cardiovascular disease. Patients with arterial hypertension are characterized by functional and structural vascular abnormalities. Vascular endothelium plays a fundamental role in modulating vascular tone and structure. The physiological production of the relaxing factors including nitric oxide, prostacyclin and hyperpolarizing relaxing factors protects the vessel wall by antagonizing the first pathogenetic steps of atherosclerosis and thrombosis. Endothelial cells may also produce endothelium-derived contracting factors. The principal component of these contracting factors is endothelin-1, which promotes the growth of the smooth muscle cells and has a vasoconstrictive and blood pressure raising effect. Defective nitric oxide production is already detectable in normotensive offspring of hypertensive patients and young essential hypertensives. A dysfunctional endothelium due to reduced nitric oxide availability associated with an increased production of oxidative stress and vasoconstricting factors is considered as an early indicator of atherothrombotic damage and of cardiovascular events also in patients with arterial hypertension. Moreover, patients with arterial hypertension are also characterized by increased arterial stiffness. This parameter, known as a sign of cardiovascular risk since the 19th century, has been shown to be a predictor of adverse cardiovascular outcome and its measurement in hypertensive patients is suggested by the European guidelines for the diagnosis and treatment of hypertension.

Left ventricular dyssynchrony in patients with left bundle branch block and patients after myocardial infarction: integration of mechanics and viability by cardiac magnetic resonance.

AIMS: To quantify left ventricular (LV) dyssynchrony in patients with left bundle branch block (LBBB) and in patients after myocardial infarction (MI) applying an accelerated three-dimensional (3D) tagging cardiac magnetic resonance (CMR) technique, and to combine dyssynchrony information with viability data obtained by late gadolinium enhancement (LGE) CMR. METHODS AND RESULTS: Thirty-two patients (59 +/- 11 years) after first MI (Pats(MI)), 10 patients (63 +/- 10 years) with LBBB (ejection fraction < 40%; Pats(LBBB<40)), 13 patients (63 +/- 11) with LBBB (ejection fraction >or= 40%; Pats(LBBB >or=40 )), and 15 healthy controls (53 +/- 10 years) underwent 3D tagging CMR and LGE imaging at 1.5 T. As a measure of mechanical LV dyssynchrony, the standard deviation of T(max) over the LV, the circumferential uniformity ratio estimate (CURE) index, and a segmental-based circumferential systolic dyssynchrony index (SDI) were calculated. All three parameters detected significantly increased circumferential dyssynchrony in patients compared with controls. The CURE and SDI showed a good correlation (r = 0.93, P < 0.0001) and detected most severe dyssynchrony in Pats(LBBB<40) (P < 0.001 vs. controls, P < 0.005 vs. Pats(MI)). Systolic dyssynchrony index additionally allowed integration of localized viability information to yield SDI(viable) which was highest in Pats(LBBB<40). CONCLUSION: Dyssynchrony patterns in the LV can be quantified globally and regionally by 3D tagging CMR. Combination of viability and dyssynchrony information allows for a comprehensive dyssynchrony quantification in patients with LBBB or post-MI. Future studies are required to test the value of the method to predict responsiveness to resynchronization.