A randomized pilot trial for aggressive therapeutic approaches in aspirin-resistant patients undergoing percutaneous coronary intervention.

BACKGROUND: There is great variability among individual patients in platelet inhibition after aspirin intake. Aspirin resistance has been associated with a higher incidence of ischemic events after percutaneous coronary intervention (PCI). The optimal antiplatelet therapy in aspirin-resistant patients undergoing PCI is unknown. The objective of this study was to evaluate whether aggressive antiplatelet therapy would reduce ischemic events in aspirin-resistant patients after PCI. METHODS: A total of 330 patients undergoing PCI (with bivalirudin) were screened for aspirin responsiveness. The resulting 36 aspirin-resistant patients were randomized into two arms: 1) conventional strategy patients received 325 mg aspirin orally and a loading dose of 600 mg clopidogrel at the time of the procedure; and 2) aggressive strategy patients received similar amounts of aspirin and clopidogrel, with the addition of an intravenous glycoprotein IIb/IIIa inhibitor bolus intraprocedurally. The primary outcome was an elevation of cardiac enzymes within 24 hours post procedure. The secondary outcome was a composite of major adverse cardiac events including death, myocardial infarction, stent thrombosis and urgent revascularization, and bleeding up to 30 days. RESULTS: Primary outcome occurred in 22% of the conventional strategy group and 11% of the aggressive strategy group (p = 0.36). The secondary outcome was reached in 27.8% of the conventional group and 5.5% of the aggressive strategy group (p = 0.17), which is suggestive of a statistical trend toward more ischemic events with conventional therapy. Importantly, there were 2 cases of definite stent thrombosis in the conventional strategy group. CONCLUSION: In aspirin-resistant patients, aggressive antiplatelet therapy tended to show better outcomes after PCI, without an increase in bleeding. These findings need validation in a large, randomized study.

Metabolic syndrome in African Americans: implications for preventing coronary heart disease.

The metabolic syndrome represents a specific clustering of cardiovascular risk factors in the same individual (abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, insulin resistance, a prothrombotic state, and a proinflammatory state). Almost 50 million American adults (about one in four) have the metabolic syndrome, which puts them at increased risk for the development of diabetes mellitus and cardiovascular disease. African Americans, especially African-American women, have a high prevalence of the metabolic syndrome. This is attributable mainly to the disproportionate occurrence in African Americans of elevated blood pressure, obesity, and diabetes. Management of the metabolic syndrome consists primarily of modification or reversal of the root causes (overweight/obesity and physical inactivity) and therapy to reduce or control the risk factors. Although all components of the metabolic syndrome should be addressed, optimal control of atherogenic dyslipidemia and elevated blood pressure may reduce cardiovascular risk by more than 80%.

Cardiovascular disease in diabetes and the cardiometabolic syndrome: focus on minority women.

Diabetes and the cardiometabolic syndrome (CMS) are evolving as global epidemics. In the United States, diabetes affects 20 million people, with 47 million afflicted with the CMS. These disorders have a higher propensity for women, particularly in minority populations with disproportionate increase in cardiovascular disease (CVD) morbidity and mortality. Despite the decline in CVD mortality rates in the general population over the past 35 years parallel to the advances in therapeutic interventions, these rates have increased in women with diabetes. Early preventive measures for CVD risk factor through behavioral and lifestyle modification, smoking cessation, and reduction in psychosocial stressors, as well as pharmacotherapy, are among the currently supported approaches to CVD risk reduction in this high-risk population. In this article, we discuss CVD in people with diabetes and the CMS, with emphasis on minority women, a particularly vulnerable population.

Stroke prevention in diabetic and other high cardiovascular risk patients.

Diabetes is a major risk factor for stroke that is usually associated with risk factors such as hypertension, obesity, albuminuria, and dyslipidemia. Furthermore, atrial fibrillation and heart failure, two of the most important risk factors of stroke, are common in the diabetic population. With the rising epidemic of diabetes, the incidence of stroke is also on the rise. Implementations of effective stroke prevention strategies appear to be the most rational option to curb this growing epidemic. In this review, we examine the epidemiologic and the pathophysiologic association between stroke and diabetes, highlighting the population-based stroke preventive measures. These include hygienic and lifestyle changes, that if applied effectively could offer a great potential for stroke prevention and reduction of the cardiovascular burden in the diabetic populations.

Control of blood pressure and other cardiovascular risk factors at different practice settings: outcomes of care provided to diabetic women compared to men.

Cardiovascular disease (CVD) is the major cause of morbidity and mortality in diabetes. To determine the proportion of patients who met the American Diabetes Association guidelines for control of CVD risk factors and to assess the achievement of these guidelines in women compared with men, we conducted a cross-sectional study of 3678 diabetic cohorts followed at seven medical centers, two Veteran Administration hospitals, three urban clinics, and two suburban clinics. Overall, 28% met the target blood pressure of <130/80 mm Hg, 48.8% achieved a goal low-density lipoprotein cholesterol of <100 mg/dL, and 35.8% had hemoglobin A1c of <7%. Gender comparisons of 2788 diabetic patients at urban and suburban centers showed that women had a lower percentage of low-density lipoprotein cholesterol <100 mg/dL (45.8 vs. 51.3, p<0.01) and a lower percentage of screening for retinopathy (54 vs. 60, p<0.01) and nephropathy (37 vs. 49, p<0.01). However, overall there were no gender differences in the percentage of patients who achieved a goal blood pressure <130/80 mm Hg or hemoglobin A1c <7%. Control of blood pressure and other CVD risk factors in diabetic patients was largely suboptimal, especially for diabetic women. These observations underscore the need for better strategies for control of CVD risk in the diabetic population in general, and women in particular.

The relationship between hyperinsulinemia, hypertension and progressive renal disease.

The incidence of end-stage renal disease (ESRD) has risen dramatically in the past decade, mainly due to the increasing prevalence of diabetes mellitus, and both impaired glucose tolerance and hypertension are important contributors to rising rates of ESRD. Obesity, especially the visceral type, is associated with peripheral resistance to insulin actions and hyperinsulinemia, which predisposes to development of diabetes. A common genetic predisposition to insulin resistance and hypertension and the coexistence of these two disorders predisposes to premature atherosclerosis. A constellation of metabolic and cardiovascular derangements, which also includes dyslipidemia, dysglycemia, endothelial dysfunction, fibrinolytic and inflammatory abnormalities, left ventricular hypertrophy, microalbuminuria, and increased oxidative stress, is referred to as the cardiometabolic syndrome. The components of this syndrome, individually and interdependently, substantially increase the risk of renal disease, cardiovascular disease (CVD) and mortality. Similar findings and cardiorenal risk factors can occur in subjects with android obesity without excess body weight.Recently, microalbuminuria has been gaining momentum as a component and marker for the cardiometabolic syndrome, in addition to being an early marker for progressive renal disease in patients with this syndrome or in those with diabetes. Furthermore, it is now established as an independent predictor of CVD and CVD mortality. This review examines the relationship between insulin resistance/hyperinsulinemia and hypertension in the context of cardiometabolic syndrome, progressive renal disease and accelerated CVD. The importance of microalbuminuria as an early marker for the cardiometabolic syndrome is also discussed in this review.

Diabetes, hypertension, and cardiovascular derangements: pathophysiology and management.

Hypertension frequently coexists with diabetes mellitus, occurring twice as frequently in diabetic as in nondiabetic persons. It accounts for up to 75% of added cardiovascular disease (CVD) risk in people with diabetes, contributing significantly to the overall morbidity and mortality in this high-risk population. Patients with hypertension are two times more prone to have diabetes than are normotensive persons. Hypertension substantially increases the risk for coronary heart disease (CHD), stroke, retinopathy, and nephropathy. In patients with type 2 diabetes, hypertension usually clusters with the other components of the cardiometabolic syndrome, such as microalbuminuria, central obesity, insulin resistance, dyslipidemia, hypercoagulation, increased inflammation, and left ventricular hypertrophy (LVH). In type 1 diabetes, hypertension often occurs subsequent to the development of diabetic nephropathy. Hypertension in people with diabetes is characterized by volume expansion, increased salt sensitivity, isolated systolic blood pressure (BP) elevation, loss of the nocturnal dipping of BP and pulse, and increased propensity toward orthostatic hypotension and albuminuria. Among the treatment strategies tested in hypertensive diabetic persons, low-density lipoprotein (LDL)-cholesterol lowering to less than 100 mg/dL and aggressive BP control to less than 130/80 mm Hg have proven effective in CVD risk reduction. The combination of two or more drugs is usually necessary to achieve the target BP.

Sudden cardiac death in patients with diabetes.

Sudden cardiac death (SCD) affects over 450,000 people in the United States annually. The mechanisms involved are poorly understood. The predictors currently known include traditional coronary heart disease risk factors, electrocardiographic abnormalities, cardiac autonomic neuropathy, left ventricular hypertrophy, cardiomyopathy, and conduction abnormalities. Diabetes mellitus and impaired glucose tolerance are of special importance due to their increased prevalence reaching epidemic proportions and the elevated risk of SCD in people with these disorders. This article reviews the current predictors of SCD with a focus on people with diabetes, hoping to offer physicians and researchers a better understanding of and a solid ground for further needed research on this important cause of premature death.

Hypertension and obesity.

Obesity is a common problem in much of the western world today in that is linked directly with several disease processes, notably, hypertension. It is becoming clear that the adipocyte is not merely an inert organ for storage of energy but that it also secretes a host of factors that interact with each other and may result in elevated blood pressure. Of particular importance is the putative role of leptin in the causation of hypertension via an activation of the sympathetic nervous system and a direct effect on the kidneys, resulting in increased sodium reabsorption leading to hypertension. Obesity per se may have structural effects on the kidneys that may perpetuate hypertension, leading to an increased incidence of end-stage renal disease that results in further hypertension. Adipose tissue may elaborate angiotensin from its own local renin-angiotensin system. The distribution of body fat is considered important in the genesis of the obesity-hypertension syndrome, with a predominantly central distribution being particularly ominous. Weight loss is the cornerstone in the management of the obesity-hypertension syndrome. It may be achieved with diet, exercise, medications, and a combination of these measures. Anti-obesity medications that are currently undergoing clinical trials may play a promising role in the management of obesity and may also result in lowering of blood pressure. Antihypertensives are considered important components in the holistic approach to the management of this complex problem.

Cardiometabolic syndrome: pathophysiology and treatment.

The cardiometabolic syndrome, an interesting constellation of maladaptive cardiovascular, renal, metabolic, prothrombotic, and inflammatory abnormalities, is now recognized as a disease entity by the American Society of Endocrinology, National Cholesterol Education Program, and World Health Organization, among others. These cardiovascular and metabolic derangements individually and interdependently lead to a substantial increase in cardiovascular disease (CVD) morbidity and mortality, making the cardiometabolic syndrome an established and strong risk factor for premature and severe CVD and stroke. Established and evolving treatment strategies including moderate physical activity, weight reduction, rigorous blood pressure control, correction of dyslipidemia, and glycemic control have proven beneficial in reversing these abnormal responses and decreasing the CVD risk.

Obesity and hypertension.

This article has discussed some of the mechanisms involved in the causal relation between obesity and hypertension. Obesity causes a constellation of maladaptive disorders that individually and synergistically contribute to hypertension, among other cardiovascular morbidities. Well-designed population-based studies are needed to assess the individual contribution of each of these disorders to the development of hypertension. In addition, because the control of obesity may eliminate 48% of the hypertension in whites and 28% in blacks, this article has offered an up-to-date on the management of this problem. It is hoped that this article will help scientists formulate a thorough understanding of obesity hypertension and form the basis for more research in this field, which has a huge impact on human life.