Dual inhibition, newer paradigms for cholesterol lowering.

Coronary heart disease (CHD) is the leading cause of death in United States. The National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III recommends new lower cholesterol levels, particularly for patients at moderate and high risk for coronary disease. Low-density lipoprotein (LDL) cholesterol is primarily the target of hypolipidemic drugs. The NCEP ATP III recommends an LDL cholesterol goal of <100 mg/dL in high-risk patients and an LDL cholesterol goal of <70 mg/dL as a therapeutic option, especially in patients with very high risk of CHD. Statins are potent LDL cholesterol-lowering drugs, but they are not as effective as fibrates and niacin in improving levels of triglycerides or high-density lipoprotein cholesterol. Ezetimibe represents a new class of hypolipidemic drugs that inhibit cholesterol absorption in the small intestine. The combination of ezetimibe with statins has been more effective than monotherapy alone in many randomized trials. LDL cholesterol reduction with statin occurs mainly with the initial dose, with relatively smaller reductions seen at higher doses. Ezetimibe was also shown to be useful in various population subgroups such as African-Americans, men and women, elderly and aged, and also those with kidney disease. We review various randomized clinical trials that used ezetimibe along with other hypolipidemic drugs like statins and fibrates. We also discuss the adverse effects of the various lipid-lowering drugs and their important drug interactions.

Role of angiotensin-converting enzyme inhibitors in vascular modulation: beyond the hypertensive effects.

Angiotensin-converting enzyme (ACE) inhibitors are being widely used as antihypertensives by clinicians worldwide. One in every three Americans has hypertension. Hypertension, diabetes, obesity, active smoking, hypercholesterolemia, and inactivity are the major cardiovascular risk factors, which can produce compounding effects on human health, leading to cardiovascular morbidity and mortality. We review the mechanism of action of ACE inhibitors and explain the rationale for using ACE inhibitors not only in hypertensive patients but also in patients with congestive heart failure, acute myocardial infarction, or coronary artery disease. ACE inhibitors can reduce preload and afterload on the heart, prevent ventricular remodeling, and even retard atherogenic changes in the vessel walls. ACE inhibitors can also be helpful in slowing the progression of kidney disease, especially in diabetics. Some studies such as the Heart Outcomes Prevention Evaluation study have shown that ACE inhibitors can reduce the risk of cardiovascular morbidity and mortality, particularly in high-risk individuals. The renin-angiotensin-aldosterone system plays an important role in regulating blood pressure and body volume in the human body. ACE inhibitors and angiotensin-receptor blockers are the two classes of antihypertensives that primarily act on the renin-angiotensin-aldosterone system. We discuss randomized, controlled trials that evaluated different ACE inhibitors and compare them with angiotensin-receptor blockers.

Combination therapy in hypertension: A focus on angiotensin receptor blockers and calcium channel blockers.

Every third adult in the United States has hypertension. Hypertension is a continuous, independent, potent risk factor for cardiovascular events like stroke, myocardial infarction, and heart failure. The blood pressure control achieved with most hypertensives is way below the recommended goal. Recent trials suggest that for nearly half of hypertensive patients, a monotherapy regimen is not adequate to control blood pressure. Investigators recommend from randomized, controlled studies that combination therapy be considered when blood pressure is above the goal of 20/10 mm Hg. In this review we discuss clinical trials that establish the need for combination therapy, with the primary focus on a new combination: calcium channel blockers (CCBs) and angiotensin receptor blockers (ARBs). ARBs and CCBs in combination can complement each other in lowering blood pressure, with a lower incidence of adverse effects, as compared with individual monotherapy components at high doses.

Therapeutic implications of diabetes in cardiovascular disease.

Insulin-resistant diabetes is becoming more prevalent among the general U.S. population. Approximately 20 million people had diabetes in 2005, of which one third of the population had impaired fasting glucose. The prevalence rate is 9%, a more alarming rate in the 20- to 39-year age group, which suggests a significant degree of how even the young are affected. We review how the prediabetic stage (impaired glucose tolerance-impaired fasting glucose and impaired glucose tolerance-impaired glucose tolerance) plays a vital role as a risk factor for cardiovascular disease, and the effectiveness of lifestyle modifications with drug therapy reduces the cardiovascular risk of early diabetes and its complications. A lifestyle modification like effective weight loss and exercise, with or without antidiabetic drugs, prevents the proatherogenic effects of diabetes. Controlled, randomized studies have shown that progression to diabetes among those with prediabetes is not inevitable; people with prediabetes who lose weight and increase their physical activity can prevent or delay diabetes and could even return their blood glucose levels to normal. Although prevention of prediabetes is a huge challenge, a tight glycemic control with lifestyle modifications and antihyperglycemics like thiazolidinediones play a vital role in increasing the insulin sensitivity of tissues and decreasing the cardiovascular risk factor of diabetes.

Pharmacotherapy plus endoscopic intervention is more effective than pharmacotherapy or endoscopy alone in the secondary prevention of esophageal variceal bleeding: a meta-analysis of randomized, controlled trials.

BACKGROUND: Previous clinical trials on the treatment of esophageal variceal bleeding yielded mixed results regarding the efficacy of endoscopic procedures compared with pharmacotherapy only. OBJECTIVE: To compare the efficacy of endoscopic procedures with that of pharmacotherapy in the prevention of mortality and rebleeding. DESIGN AND SETTING: A systematic literature review was performed to identify randomized, controlled trials of the efficacy of pharmacotherapy and endoscopic therapy. A meta-analysis was performed by using the Comprehensive MetaAnalysis software package. A 2-sided alpha error <.05 was considered statistically significant (P < .05). PATIENTS: Twenty-five clinical trials with a total of 2159 patients were eligible for meta-analysis. OUTCOME MEASUREMENTS: Relative risk (RR) with 95% confidence interval (CI) was computed for all-cause mortality, mortality from rebleeding, all-cause rebleeding, and rebleeding caused by varices. RESULTS: Pharmacotherapy was as effective as endoscopic procedures in preventing rebleeding (RR 1.067; 95% CI, 0.865-1.316; P = .546), variceal rebleeding (RR 1.143; 95% CI, 0.791-1.651; P = .476), all-cause mortality (RR 0.997; 95% CI, 0.827-1.202, P = .978), and mortality from rebleeding (RR 1.171; 95% CI, 0.816-1.679; P = .39). Pharmacotherapy combined with endoscopic procedures did not reduce all-cause mortality (RR 0.787; 95% CI, 0.587-1.054; P = .108) or mortality caused by rebleeding (RR 0.786; 95% CI, 0.445-1.387; P = .405) compared with endoscopic procedures. However, combination therapy (endoscopic procedure plus pharmacotherapy) significantly reduced the incidence of all rebleeding (RR 0.623; 95% CI, 0.523-0.741; P < .001) and variceal rebleeding (RR 0.601; 95% CI, 0.440-0.820; P < .001). LIMITATIONS: Heterogeneity of patient population and different treatment protocols may have affected our meta-analysis. CONCLUSION: Pharmacotherapy may be as effective as endoscopic therapy in reducing rebleeding rates and all-cause mortality. Pharmacotherapy plus endoscopic intervention is more effective than endoscopic intervention alone.

Endurance exercise and resistance training in cardiovascular disease.

Contrary to the age old taboo of exercise in cardiac patients, resistance training has been gaining importance recently as a safe, healthy fitness option in prevention of cardiovascular diseases, the leading killer disease in the population above 45 years in the United States. Endurance or aerobic exercise helps improve overall stamina and the ability of the heart to pump oxygenated blood in those with and without prior cardiovascular disease. In addition to modifying cardiovascular risks, resistance training has profound beneficial effects on improving muscle strength and endurance, preventing osteoporosis and improving quality of life both in the healthy and cardiovascular patients including women and heart failure patients. So resistance training should be regarded as a complementary fitness program rather that a substitute to endurance training. This review discusses the physiological phenomenon and benefits of exercise training programs on cardiovascular disease patients focusing on endurance exercise and resistance training.