Search

The identification of patients at high risk for cardiovascular events is imperative in the reduction of cardiovascular mortality and morbidity. Although coronary artery disease, peripheral arterial disease, cerebrovascular disease, hypertension, and diabetes mellitus contribute to the risk of developing cardiovascular events, we are now faced with emerging fronts because of an increase in life expectancy and the epidemic of hypertension, obesity, metabolic syndrome, and diabetes. Recent data emphasize the beneficial role of renin-angiotensin-aldosterone system (RAAS) blockers. This article addresses the role of RAAS activation in the high-risk metabolic milieu and the role of angiotensin receptor blockers in targeting and inhibiting the RAAS for cardiovascular protection.

This article reviews the results from several recent reports describing the safety and efficacy of statin therapy in the setting of heart failure. It additionally discusses the ongoing controversy regarding the lipid paradox and possible mechanisms responsible for potential benefit of statin therapy in heart failure.

The role of the RAAS in development and maintenance of blood pressure is well established. In addition, the deleterious effects of angiotensin II on the heart, vasculature, and kidneys have been clearly defined. There seems to be a close relationship between endothelial dysfunction, insulin resistance (a precursor to diabetes and coronary artery disease) and angiotensin II. The signaling pathways for insulin in the vascular wall interacts with the angiotensin signaling, giving rise to potential mechanisms for development of diabetes and resulting harmful effects. A large number of clinical trials using ACE inhibitors or ARBs have shown significant reduction in secondary endpoints in the development of new onset of diabetes. Ongoing prospective studies involving ARBs (eg, the Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research trial) and ACE inhibitors (eg, the Diabetes Re-duction Assessment with Ramipril and Rosiglita-zone Medication trial) are testing the ability of certain agents to prevent type 2 diabetes. In the meantime, it is important to recognize insulin resistance and metabolic syndrome as entities that increase the risk for cardiovascular disease. In addition to lifestyle modifications, managing endothelial dysfunction and protecting the vasculature will help prevent diabetes and cardiovascular disease.

Large, placebo-controlled RCTs that involve only diabetic patients who have hypertension have not been performed. Subgroup analyses of hyper-tension control from several recent RCTs un-equivocally demonstrated greater benefit in diabetic populations (see Table 3) with ACE inhibitors, TDs, and CCBs. Treatment with fBs(atenolol) also was beneficial in diabetic patients who had hypertension in the actively-controlled UKPDS. The results of three RCTs support intensive BP control in diabetic patients (see Table 4). In these trials, diabetic patients gained more benefit than nondiabetic patients. Such an effect is consistent with the fact that diabetics are at higher risk for CV events. Although there are limited data from RCTs with head-to-head comparison of newer agents (eg,ACE inhibitors, ARBs, CCBs) to show that these drugs are better than diuretics and betaBs in reducing CV events by treating hypertension in the diabetic population, the available data support ACE inhibitors (and ARBs if ACE inhibitors are not tolerated) as an initial drug of choice in diabetic,hypertensive patients (see Table 5). Most diabetic patients require three or four drugs to control their BP to target range; as such, it is not necessary to justify the choice of any single class of drug. Tight BP control is cost-effective and is more rewarding than hyperglycemic control in diabetic,hypertensive patients. The optimal goal in diabetics should be to achieve BP that is less than 130/80 mm Hg. Appropriate action should be taken if BP is greater than 140/85 mm Hg. In subjects who have diabetes and renal insufficiency,the BP should be decreased to less than 125/75 mm Hg to delay the progression of renal failure. Limited data suggest that an ACE inhibitor or an ARB is the agent of choice, especially in patients who have proteinuria or renal insufficiency. betaBs can be the first-line agent in diabetics who have CAD. TDs and CCBs are the second line drugs.AAAs should be avoided. Most hypertensive patients require more than one agent to adequately control their BP. There is no evidence to support one combination regimen over the others, nevertheless, the combination of an ACE inhibitor with a TD or a fPB may be more beneficial and cost effective than other combinations in the diabetic population. Large outcome studies that compare different combination therapies in hypertensive,diabetic patients are needed.

As we enter the twenty-first century, the burden of chronic diseases, such as obesity, type 2 diabetes, and CVDs, is expected to increase dramatically. These diseases are a consequence of several factors that include an aging population,changes in demographic composition, and an excess of contemporary lifestyle. The prevention and control of overweight, obesity, metabolic syndrome, and diabetes pose special challenges for clinical and public heath practice as well as for basic, clinical, and population science research.

Diabetes is a vascular disease. Endothelial dysfunction is the initial process in vascular manifestations of diabetes mellitus (DM). There are multiple pathways involved in the pathophysiologic process related to endothelial dysfunction in DM. Most of these abnormalities occur secondary to insulin resistance. In this article the role of insulin, glucose,dyslipidemia, oxidative stress and various cellular mechanisms related to endothelial dys-function in diabetes are discussed in detail.

Although a large number of clinical studies during the past decade have documented that myocardial ischemia, acute myocardial infarction, and sudden cardiac death have definite circadian patterns, recently published work suggests that it is not necessarily a specific time of the day but the sleep/wake cycle and postural changes as well as the balance between triggers and protective factors that determine the onset of cardiovascular events. A clear understanding of the pathophysiologic processes responsible for ischemic events and the specific roles played by various triggers would be helpful in better defining the therapeutic strategies designed for the prevention and treatment of acute cardiac events. Because changes in hemodynamic parameters are of paramount importance in initiating an ischemic event, it is critical to review their role and relationship in the pathogenesis of acute coronary events.

A clear understanding of the hemodynamic changes involved in the pathophysiologic process responsible for the genesis of myocardial ischemia is essential for the selection of the most appropriate anti-ischemic therapy. Based on the predominant mechanism responsible for myocardial ischemia, the therapeutic choice can vary widely.

The medical management of patients with CHF and ventricular arrhythmias is one of the most challenging clinical situations frequently encountered by physicians on a daily basis. Reviewed and examined in this article are available data regarding the clinical relevance and prevalence of ventricular arrhythmias, their prognostic importance in patients with CHF, and the role of available therapeutic modalities and their limitations in the management of these patients.

Heart failure is a frequently encountered clinical condition with an extremely guarded short- and long-term prognosis. Although recently a great deal of effort has been directed toward early recognition and aggressive treatment of patients with heart failure, considerable work lies ahead if we are to alter the overall prevalence of CHF and reduce the excessive mortality associated with it. Because the prognosis is poor after the onset of heart failure, it seems logical to direct public health measures toward prevention of this condition.

Identification of accurate predictors of mortality in patients with heart failure is important in making rational treatment decisions as well as in the design of clinical trials. The following four categories of variables have been found to be independent predictors of mortality: 1) functional capacity, 2) hemodynamic measures of cardiac pump performance, 3) spontaneous arrhythmias, and 4) laboratory evidence of neurohormonal activation. Within each category, multiple variables are predictive and are correlated with each other. These variables are operative only over a 1- to 5-year time period. Most patients with clinically manifest heart failure undergo inexorable disease progression and die within 10 years of diagnosis, despite important recent advances in the pharmacologic treatment of this syndrome.

Considerable efforts have been made during the past decade to understand better the pathophysiologic processes involved in LV remodeling and the progression of LV dysfunction. A clear understanding of the pathogenetic mechanism has resulted in the search for the ideal therapeutic approach to prevent such progression. The main focus of this article is to review the recent progress in this area and to discuss the results of several large clinical trials that have demonstrated the benefit of early intervention to prevent heart failure and progression of cardiac dysfunction.

Transient episodes of myocardial ischemia can be reliably detected by AEM in patients with known CAD. AEM appears to be particularly useful for patients in whom symptom control has been achieved with conventional antianginal drugs because many of these patients (up to 50%) continue to have residual silent ischemia that would otherwise remain undetected. Despite the lack of symptoms, numerous studies in patients with stable and unstable coronary syndromes have shown that the presence of silent ischemia during AEM is associated with an increased risk of subsequent coronary events and cardiac death. Although Holter monitoring is a practical and reliable tool for prolonged evaluation of myocardial ischemia, its routine use can not be advocated until its clinical role has been clearly defined in the ongoing large prospective studies.

The preceding review indicates that silent myocardial ischemia has definite prognostic implications in both symptomatic and asymptomatic patients with coronary artery disease. Patients surviving an acute myocardial infarction are at a particularly high risk if they show evidence of myocardial ischemia. At present, many noninvasive diagnostic modalities are available to the physician for the evaluation of symptomatic and silent myocardial ischemia in such patients. Because as many as 30 per cent of patients may become asymptomatic after myocardial infarction, physicians must be aggressive in evaluating their patients for the presence of silent myocardial ischemia. The presence of silent ischemia would help identify those patients at high risk of postinfarction complications. Future use of currently available therapeutic modalities directed toward treatment of total ischemic burden on the myocardium may help lower morbidity and mortality in these patients by reducing the risk of subsequent cardiac events.