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Kones R.,The Cardiometabolic Research Institute
Drug Design, Development and Therapy | Year: 2010

The major public health concern worldwide is coronary heart disease, with dyslipidemia as a major risk factor. Statin drugs are recommended by several guidelines for both primary and secondary prevention. Rosuvastatin has been widely accepted because of its efficacy, potency, and superior safety profile. Inflammation is involved in all phases of atherosclerosis, with the process beginning in early youth and advancing relentlessly for decades throughout life. C-reactive protein (CRP) is a well-studied, nonspecific marker of inflammation which may reflect general health risk. Considerable evidence suggests CRP is an independent predictor of future cardiovascular events, but direct involvement in atherosclerosis remains controversial. Rosuvastatin is a synthetic, hydrophilic statin with unique stereochemistry. A large proportion of patients achieve evidence-based lipid targets while using the drug, and it slows progression and induces regression of atherosclerotic coronary lesions. Rosuvastatin lowers CRP levels significantly. The Justification for Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial was designed after the observation that when both low density lipoprotein and CRP were reduced, patients fared better than when only LDL was lowered. Advocates and critics alike acknowledge that the benefits of rosuvastatin in JUPITER were real. After a review, the US Food and Drug Administration extended the indications for rosuvastatin to include asymptomatic JUPITER-eligible individuals with one additional risk factor. The American Heart Association and Centers of Disease Control and Prevention had previously recognized the use of CRP in persons with "intermediate risk" as defined by global risk scores. The Canadian Cardiovascular Society guidelines went further and recommended use of statins in persons with low LDL and high CRP levels at intermediate risk. The JUPITER study focused attention on ostensibly healthy individuals with "normal" lipid profiles and high CRP values who benefited from statin therapy. The backdrop to JUPITER during this period was an increasing awareness of a rising cardiovascular risk burden and imperfect methods of risk evaluation, so that a significant number of individuals were being denied beneficial therapies. Other concerns have been a high level of residual risk in those who are treated, poor patient adherence, a need to follow guidelines more closely, a dual global epidemic of obesity and diabetes, and a progressively deteriorating level of physical activity in the population. Calls for new and more effective means of reducing risk for coronary heart disease are intensifying. In view of compelling evidence supporting earlier and aggressive therapy in people with high risk burdens, JUPITER simply offers another choice for stratification and earlier risk reduction in primary prevention patients. When indicated, and in individuals unwilling or unable to change their diet and lifestyles sufficiently, the benefits of statins greatly exceed the risks. Two side effects of interest are myotoxicity and an increase in the incidence of diabetes. © 2010 Kones, publisher and licensee Dove Medical Press Ltd. Source

The potential importance of both prevention and personal responsibility in controlling heart disease, the leading cause of death in the USA and elsewhere, has attracted renewed attention. Coronary artery disease is preventable, using relatively simple and inexpensive lifestyle changes. The inexorable rise in the prevalence of obesity, diabetes, dyslipidemia, and hypertension, often in the risk cluster known as the metabolic syndrome, drives the ever-increasing incidence of heart disease. Population-wide improvements in personal health habits appear to be a fundamental, evidence based public health measure, yet numerous barriers prevent implementation. A common symptom in patients with coronary artery disease, classical angina refers to the typical chest pressure or discomfort that results when myocardial oxygen demand rises and coronary blood flow is reduced by fixed, atherosclerotic, obstructive lesions. Different forms of angina and diagnosis, with a short description of the significance of pain and silent ischemia, are discussed in this review. The well accepted concept of myocardial oxygen imbalance in the genesis of angina is presented with new data about clinical pathology of stable angina and acute coronary syndromes. The roles of stress electrocardiography and stress myocardial perfusion scintigraphic imaging are reviewed, along with the information these tests provide about risk and prognosis. Finally, the current status of gender disparities in heart disease is summarized. Enhanced risk stratification and identification of patients in whom procedures will meaningfully change management is an ongoing quest. Current guidelines emphasize efficient triage of patients with suspected coronary artery disease. Many experts believe the predictive value of current decision protocols for coronary artery disease still needs improvement in order to optimize outcomes, yet avoid unnecessary coronary angiograms and radiation exposure. Coronary angiography remains the gold standard in the diagnosis of coronary artery obstructive disease. Part II of this two part series will address anti-ischemic therapies, new agents, cardiovascular risk reduction, options to treat refractory angina, and revascularization. © 2010 Kones, publisher and licensee Dove Medical Press Ltd. Source

Kones R.,The Cardiometabolic Research Institute
Hospital practice (1995) | Year: 2014

Despite remarkable decreases in the mortality of coronary heart disease, there is concern that continued high levels of cardiovascular risk in the population may reverse these gains. By 2015, the prevalence of cardiovascular disease in the United States will be 37.8%. Obesity, hypertension, dyslipidemia, diabetes mellitus (DM), metabolic syndrome, and inflammation are the primary components driving cardiovascular risk. Approximately 70% of adults are overweight or obese, yet diet quality continues to deteriorate and authoritative information is insufficiently promoted. More than half of US adults have lipid abnormalities; 27% of US adults have high values of low-density lipoprotein cholesterol, 23% have low values of high-density lipoprotein cholesterol concentrations, and 30% have high triglyceride levels. Approximately 34% of adults have hypertension; 40% of these adults are unaware of the diagnosis. In patients with hypertension who are treated, 54% remain uncontrolled. The prevalence of hypertension in elderly patients has increased from 35% to 41%. In addition, 30% of adults have prehypertension. The burden of hypertension alone accounts for approximately 1000 deaths per day. Trends in the prevalence of glucose intolerance are similar. The prevalence of DM is approximately 12%, with 27% of cases remaining undiagnosed. Thirty-five percent of US adults aged > 20 years have prediabetes and 7.3% of adults are unaware of the diagnosis. If the present trends continue, 1 in 3 of US adults will have DM by 2050. Participation in exercise has been low and a "straight line" for > 2 decades. Accelerometer data indicate that individuals who attain minimal exercise goals are only a fraction of the often quoted levels of > 35%. Control of risk factors in primary prevention, although improved, remains decidedly incomplete. Lowering the burden of cardiovascular risk factors at the population level has been exceptionally difficult. For reasons outlined, the solution to this problem is multifaceted and extends well beyond the delivery of medical care into the structure of society and the environment. Source

Kones R.,The Cardiometabolic Research Institute | Rumana U.,The Cardiometabolic Research Institute
Cardiology Clinics | Year: 2014

Classical angina refers to typical substernal discomfort triggered by effort or emotions, relieved with rest or nitroglycerin. The well-accepted pathogenesis is an imbalance between oxygen supply and demand. Goals in therapy are improvement in quality of life by limiting the number and severity of attacks, protection against future lethal events, and measures to lower the burden of risk factors to slow disease progression. New pathophysiological data, drugs, as well as conceptual and technological advances have improved patient care over the past decade. Behavioral changes to improve diets, increase physical activity, and encourage adherence to cardiac rehabilitation programs, are difficult to achieve but are effective. © 2014 Elsevier Inc. Source

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