The Effect of Calcium Channel Blockers on Moderate or Severe Albuminuria in Diabetic, Hypertensive Patients.

OBJECTIVES: Inhibitors of the renin-angiotensin system are recommended for the management of albuminuria in patients with hypertension and diabetes mellitus, but there is little consensus about alternative therapies. Calcium channel blockers are recommended for the management of hypertension, but the data are controversial regarding their role in patients with albuminuria. This review was designed to assess the efficacy of calcium channel blockers compared with inhibitors of the renin-angiotensin system in decreasing albuminuria in diabetic, hypertensive patients with nephropathy. METHODS: We searched MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov for records that compared calcium channel blockers to inhibitors of the renin-angiotensin system and reported pre- and postintervention albuminuria measurements. Two reviewers independently screened abstracts for randomized, controlled trials in adults. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to select 29 trials from 855 records. We synthesized the data through a random-effects model. RESULTS: We analyzed data from 2113 trial participants with hypertension and diabetes mellitus who had the equivalent of ≥30 mg/day of urinary albumin excretion. Inhibitors of the renin-angiotensin system were more effective than calcium channel blockers in decreasing albuminuria (standardized difference in means -0.442; confidence interval, -0.660 to -0.225; P < .001). This finding was independent of the blood pressure response to treatment. There was no difference between the 2 drug classes regarding markers of renal function. CONCLUSIONS: Inhibitors of the renin-angiotensin system are superior to calcium channel blockers for the reduction of albuminuria in nephropathy due to hypertension and diabetes mellitus. The net clinical benefit, however, is small.

The Effect of Vegan Diets on Blood Pressure in Adults: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Vegan diets are increasing in popularity and have beneficial effects on glycemia and blood lipids, but the evidence is inconclusive regarding their effect on blood pressure. The purpose of this study was to review the effect of vegan diets on blood pressure in adults. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov for records that compared a vegan diet with any less restrictive diet and reported pre- and postintervention systolic and diastolic blood pressures. Two reviewers independently screened abstracts for randomized, controlled clinical trials in individuals ≥18 years of age and older. We used the PRISMA guidelines to select 11 clinical trials from 1673 records. Data synthesis was performed through a random-effects model. RESULTS: The pooled data included 983 participants. Compared with less restrictive diets, a vegan diet did not result in a significant change in systolic (-1.33 mm Hg; 95% confidence interval [CI], -3.50-0.84; P = .230) or diastolic (-1.21 mm Hg; 95% CI, -3.06-0.65; P = .203) blood pressure. A prespecified subgroup analysis of studies with baseline systolic blood pressure ≥130 mm Hg revealed that a vegan diet resulted in a mean decrease in the systolic (-4.10 mm Hg; 95% CI, -8.14 to -0.06; P = .047) and diastolic (-4.01 mm Hg; 95% CI, -5.97 to -2.05; P = 0.000) blood pressures. CONCLUSION: The changes in blood pressure induced by a vegan diet without caloric restrictions are comparable with those induced by dietary approaches recommended by medical societies and portion-controlled diets.

A Rare Cause of Dysphagia and Cough: Bronchoesophageal Fistula from Silicosis.

Dysphagia and cough in an older male smoker raise concern for malignancy. However, a history of environmental exposures led to a much more interesting diagnosis in this case of pneumoconiosis due to silicosis. Silicosis is an uncommon pulmonary disease with rare associated gastrointestinal symptoms. We report a bronchoesophageal fistula resulting from silicosis causing dysphagia and cough. This is the first report of using endoscopic stenting to manage an esophageal fistula from silicosis. This case highlights how common symptoms of cough and dysphagia can masquerade as a pulmonary or oropharyngeal problem, when they are actually gastrointestinal manifestations of a rare disease.

Central sympatholytic drugs.

KEY POINTS: • Central sympatholytic drugs reduce blood pressure mainly by stimulating central α(2) -adrenergic receptors in the brainstem centers, thereby reducing sympathetic nerve activity and neuronal release of norepinephrine to the heart and peripheral circulation. • This class of drugs, however, is currently used mainly as fourth-line (or beyond) drug therapy for hypertension because of side effects of drowsiness, fatigue, and dry mouth. • Rebound hypertension is also another major concern in certain drugs with a short half-life, particularly in patients who are nonadherent to the regimen. Therefore, their use on a "PRN" basis for treatment of blood pressure surge in the absence of symptoms or acute target complications should also be avoided.

Association between transforming growth factor-beta(1) and left ventricular mass and diameter in hypertensive patients.

Angiotensin II influences development of left ventricular hypertrophy (LVH) by stimulating cardiomyocyte hypertrophy, fibroblast proliferation, and collagen synthesis. Because pro-fibrotic actions of angiotensin may be mediated by increased production of transforming growth factor-beta(1) (TGF-beta(1)), we assessed whether serum TGF-beta(1) levels might reflect involvement in LVH development. We analyzed relationships between left ventricular mass and levels of renin, aldosterone, and TGF-beta(1) in 67 hypertensive subjects (mean age 64 +/- 11.3 years) with electrocardiographic evidence of LVH. Levels were obtained after a 2-week washout of antihypertensive medications; two-dimensional echocardiography was subsequently performed. Linear regression analysis showed a correlation between TGF-beta(1) and LV mass (r = 0.36, P = .002). This was apparently explained by the correlation between TGF-beta(1) and left ventricular diastolic internal diameter (r = 0.42, P < .001), because no correlation between TGF-beta(1) levels and LV wall thickness was found. In multivariate analysis, the correlation between TGF-beta(1) and internal diameter remained significant (r = 0.39, P = .0014). There were no racial differences in levels of TGF-beta(1) or left ventricular geometry, and no correlations between age, blood pressure, renin, aldosterone, and left ventricular mass or dimensions. These findings indicate that serum TGF-beta(1) levels are related to left ventricular structure in hypertensive subjects, suggesting its possible involvement in the process of hypertensive left ventricular remodeling.

The renin-angiotensin aldosterone system: pathophysiological role and pharmacologic inhibition.

BACKGROUND: The renin-angiotensin aldosterone system (RAAS) is a hormonal cascade that functions in the homeostatic control of arterial pressure, tissue perfusion, and extracellular volume. Dysregulation of the RAAS plays an important role in the pathogenesis of cardiovascular and renal disorders. OBJECTIVES: To review the role of the RAAS in the development of hypertensive cardiovascular disease and related conditions and provide an overview of the classes of pharmacologic agents that inhibit this system. RESULTS: The RAAS is initiated by the regulated secretion of renin, the rate-limiting enzyme that catalyzes the hydrolysis of angiotensin (Ang) I from the N-terminus of angiotensinogen. Ang I is in turn hydrolyzed by angiotensin-converting enzyme (ACE) to form Ang II, a potent vasoconstrictor and the primary active product of the RAAS. Recent evidence has suggested that other metabolites of Ang I and II may have biological activity, particularly in tissues. Development of agents that block the RAAS (e.g., beta blockers, ACE inhibitors [ACE Is], and angiotensin receptor blockers [ARBs]) began as a therapeutic strategy to treat hypertension. Preclinical and clinical studies have indicated important additional cardiovascular and renal therapeutic benefits of ACE Is and ARBs. However, blockade of the RAAS with these agents is incomplete. CONCLUSION: Therapeutic approaches that target more complete inhibition of the RAAS may offer additional clinical benefits for patients with cardiovascular and renal disorders. These approaches may include dual blockade using ACE Is and ARBs in combination, or new therapeutic modalities such as direct renin inhibition with aliskiren, recently approved for the treatment of hypertension.

Clinical events in high-risk hypertensive patients randomly assigned to calcium channel blocker versus angiotensin-converting enzyme inhibitor in the antihypertensive and lipid-lowering treatment to prevent heart attack trial.

The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) provides a unique opportunity to compare the long-term relative safety and efficacy of angiotensin-converting enzyme inhibitor and calcium channel blocker-initiated therapy in older hypertensive individuals. Patients were randomized to amlodipine (n=9048) or lisinopril (n=9054). The primary outcome was combined fatal coronary heart disease or nonfatal myocardial infarction, analyzed by intention-to-treat. Secondary outcomes included all-cause mortality, stroke, combined cardiovascular disease (CVD), end-stage renal disease (ESRD), cancer, and gastrointestinal bleeding. Mean follow-up was 4.9 years. Blood pressure control was similar in nonblacks, but not in blacks. No significant differences were found between treatment groups for the primary outcome, all-cause mortality, ESRD, or cancer. Stroke rates were higher on lisinopril in blacks (RR=1.51, 95% CI 1.22 to 1.86) but not in nonblacks (RR=1.07, 95% CI 0.89 to 1.28), and in women (RR=1.45, 95% CI 1.17 to 1.79), but not in men (RR=1.10, 95% CI 0.92 to 1.31). Rates of combined CVD were higher (RR=1.06, 95% CI 1.00 to 1.12) because of higher rates for strokes, peripheral arterial disease, and angina, which were partly offset by lower rates for heart failure (RR=0.87, 95% CI 0.78 to 0.96) on lisinopril compared with amlodipine. Gastrointestinal bleeds and angioedema were higher on lisinopril. Patients with and without baseline coronary heart disease showed similar outcome patterns. We conclude that in hypertensive patients, the risks for coronary events are similar, but for stroke, combined CVD, gastrointestinal bleeding, and angioedema are higher and for heart failure are lower for lisinopril-based compared with amlodipine-based therapy. Some, but not all, of these differences may be explained by less effective blood pressure control in the lisinopril arm.