The significance of hypothermia in preserving ischemic myocardium.

The clinical use of mild hypothermia to preserve ischemic cardiac and cerebral tissue continues to grow in popularity. This is a result of the known fact that hypothermia reduces myocardial oxygen demands more than any other intervention. The Advanced Life Support (ALS) Task Force of the International Liaison Committee on Resuscitation (ILCOR) made the following recommendations a year ago, in October 2002: "Unconscious adult patients with spontaneous circulation after out-of-hospital cardiac arrest should be cooled to 32 degrees C to 34 degrees C for 12 to 24 hours when the initial rhythm was VF," or in-hospital even when arrest is due to other rhythms. Therapeutic use of hypothermia is in progress.

Anger and acute coronary events.

A high level of anger has a powerful effect on the incidence of preventable cardiovascular death. Persuasive clinical evidence indicates that anger evokes physiological responses that are potentially life-threatening in the setting of CAD. Finally, emotional stress, anger, or worry have a dominant influence on the severity, frequency, and treatment of angina. The natural history of angina is characterized by episodic variations in the frequency and severity of symptoms coincident with periods of emotional stress. When angina is associated with periods of emotional stress or anger, the angina is not usually a result of progressive coronary disease, but rather is due to an increase in oxygen demand. Appreciation of this concept will help to rule out "true" unstable angina due to progressive coronary disease from recurrent angina that results from an increase in oxygen demand related to emotional stress. The former requires aggressive medical or surgical therapy; the latter, a demand-induced angina, responds to beta-adrenergic blockade and a tranquilizer.

Seminal changes in the management of the acute coronary event: current concepts.

In the past era, we held high-grade arterial stenosis responsible for the acute complications of atherosclerosis. These concepts are being reassessed. Qualitative rather than quantitative aspects of plaques (e.g., inflammation rather than plaque size) have been established as decisive determinants of their probabilities to cause acute complications. Numerous beneficial effects of statins have been demonstrated. These include lipid lowering, plaque stability, enhanced endothelial function, and antiplatelet, antiatherothrombotic, and antimacrophage activities. However, the successful medical management of CAD is also multifactorial and in addition to use of statins include beta-blockers, ACE inhibitors, and aspirin, as well as blood pressure control, diet, and exercise (see [figure: see text] Figure). The results have been not only the preventions of acute complications of atherosclerosis, but also the successes in stabilizing acute coronary events and preventing infarctions.

Obesity and the metabolic syndrome.

The prevalence of marked obesity is increasing rapidly among adults and has more than doubled in 10 years. Sixty-one percent of the adult population of the United States is overweight or obese. Americans are the fattest people on earth. Paradoxically these increases in the numbers of persons who are obese or overweight have occurred during recent years when Americans have been preoccupied with numerous dietary programs, diet products, weight control, health clubs, home exercise equipment, and physical fitness videos, each "guaranteed" to bring rapid results. Overweight and obesity are also world problems. The World Health Organization estimates that 1 billion people around the world are now overweight or obese. Westernization of diets has been part of the problem. Fruits, vegetables, and whole grains are being replaced by readily accessible foods high in saturated fat, sugar, and refined carbohydrates. Since class 3 obesity (morbid or extreme obesity) is associated with the most severe health complications, the incidence of hypertension, stroke, heart disease, diabetes, and peripheral vascular disease will increase substantially in the future. Recently, obesity alone has been implicated in the development of cardiac hypertrophy and CHF. The metabolic syndrome associated with abdominal obesity, which includes insulin resistance, dyslipidemia, and elevated CRP levels, identifies subjects who have an increase in cardiovascular morbidity and mortality. Twenty to 25% of the adult population in the United States have the metabolic syndrome, and in some older groups this prevalence approaches 50%. The prevalence of overweight children in the United States has also been increasing dramatically, especially among non-Hispanic blacks and Mexican-American adolescents. Overweight children usually become overweight adults. Atherosclerosis begins in childhood. The degree of atherosclerotic changes in children and young adults can be correlated with the presence of the same risk factors seen in adults. As health providers, our direction is obvious!

A quick test predicts acute coronary events.

Inflammation of the coronary arterial wall plays a major role in atherosclerosis and ultimately thrombosis by contributing to vascular constriction, spasm, and thrombus formation. Measurement of hs-CRP level is a readily available laboratory blood test that serves as a gauge of coronary plaque inflammation. As a result, hs-CRP has become a very useful biological marker for predicting the risk of acute coronary events and for making decisions regarding treatment. It is important to recognize that lipid-lowering therapy decreases plaque inflammation and slows the progression of calcium buildup in the coronary arteries, which is readily verified by reduction in hs-CRP levels. Endothelial dysfunction is a product of plaque inflammation and as such can predict acute CV events. Endothelial function can be assessed during cardiac catheterization by measuring the vasoactive response to pharmacological or physiological stress. However, the routine use of cardiac catheterization to measure drug-induced coronary vasoactivity can have potential adverse effects in patients with unstable coronary disease. Time and costs can also be additional constraints in the routine use of this procedure. Consequently the simple and readily available hs-CRP test is accurate and preferable.

The cocaine-abused heart.

Recreational use of cocaine dates back to the Incas in South America 5000 years ago. Cocaine is derived from the leaves of Erythroxylon coca, a shrub native to South America. In the late 1800s, Sigmund Freud popularized the drug in Europe. He used cocaine to treat depression, asthma, cachexia, and for overcoming morphine addiction. Also in this period cocaine rapidly gained acceptance in surgical procedures as a local anesthetic and vasoconstrictor. Cocaine reached the United States in the early 1900s, and its popularity led President Taft to declare it public enemy number one in 1910. Cocaine became popular again in the 1980s. Currently cocaine use is responsible for more ED visits then any of the other illicit drugs. Because most cocaine users are young, they are at a lower risk for coronary artery atherosclerotic disease. An estimated 25 million people between the ages of 26 and 34 years have used cocaine at least once, 20% were women and 30% men. Habitual users of cocaine are estimated to number 1.5 million. Most cocaine-induced chest pains do not progress to MI, and in fact many originate in the chest wall. The chest pains due to cocaine, however, are induced by myocardial ischemia, a result of vasospasm and not a thrombotic occlusion of a coronary artery that has a ruptured atheromatous plaque. ECG findings can be misleading in the diagnosis because the early repolarization syndrome, a normal variant, is a frequent finding in young African American men. Measurement of cardiac troponin levels is the most reliable diagnostic test. Percutaneous coronary intervention and angioplasty, rather than thrombolysis, is the treatment of choice because intense coronary vasospasm is the primary pathophysiology in cocaine-induced MI.

Diuretics, the most critical therapy in heart failure, yet often neglected in the literature.

Dietary sodium restriction and diuretics are basic requirements in the treatment of CHF. The reduction in pulmonary venous congestion following the use of diuretics leads to a rapid improvement in dyspnea, promotes natriuresis without direct positive inotropic effects, and does not reflexively activate the neuroendocrine system. The recent literature has been replete with reports on the treatment of HF. However, very little has been said about the importance and the methods of use of diuretics in HF. Treatment of HF cannot succeed without regard for the role of the sodium ion in HF. There are nearly 5 million cases of HF in the United States. More than 500,000 new cases are diagnosed each year. Hospital discharges and deaths due to HF have increased more than 100% in the past 2 decades with a 5-year mortality rate close to 50%. Since the leading cause of HF in Western countries is ischemic heart disease, aggressive therapy to halt progression of coronary atherosclerosis can have a major impact on controlling and often curing HF.

Cardiac repair with autologous bone marrow stem cells.

All adults have stem cells in their body that can act like embryonic stem cells when given an appropriate stimulus. When VEGF is given, the bone marrow is stimulated to release stem cells, which grow new coronary arteries and also replenish damaged or dead cardiomyocytes. Transplanting autologous bone marrow stem cells into coronary arteries reduced infarct size, improved the prognosis following an acute MI and in patients with chronic congestive heart failure. Since patients are the source of their own stem cells, there would be a ready supply, with no rejection or immunological issues, and political debate on stem cell research would end. It is worth noting that statin therapy stimulates mobilization of EPCs, which repair damaged or dead myocardial cells and stimulate growth of new coronary arteries.

The resurrection of spironolactone on its golden anniversary.

The edematous states, specifically those in CHF and cirrhosis of the liver, are associated with excessive aldosterone secretion and represent states of secondary hyperaldosteremia. Aldosterone promotes sodium retention by the renal tubules. Spironolactone, first introduced 50 years ago (1953), blocks the action of aldosterone on renal transport of electrolytes, thus acting as an effective diuretic, and in addition, has potentiating effects on other diuretics, including the thiazides. Spironolactone has undesirable side effects that have limited its clinical use; the most significant are impotence, gynecomastia, and hirsutism. Eplerenone, a recently introduced selective ARA, decreases morbidity and mortality in patients with CHF following MI and has none of the androgenic or estrogenic side effects of spironolactone. Eplerenone is an effective alternative for spironolactone.

Statin pleiotropy: fact or fiction?

Accumulating evidence from clinical trials and basic research indicates that statin therapy favorably influences a number of diverse clinical events through both effects related to lowering of LDL cholesterol levels and effects independent of the lowering of LDL cholesterol levels. The latter effects are referred to as pleiotropic. The full potential of this exciting class of drugs in vascular and nonvascular protection is only just being realized. The pleiotropic effects of the statins improve vascular relaxation, promote new vessel formation, and stabilize unstable plaques. Statins reduce glomerular injury, renal disease progression, insulin resistance, and bone resorption. Ezetimibe, a recently approved medication, enhances the lipid-lowering effects of the statins by lowering LDL and increasing HDL levels through its property of inhibiting absorption of cholesterol in the small intestine. These salutary effects of ezetimibe on statin levels presumably enhance the beneficial effects attributed to statin pleiotropy. It is noteworthy that the pleiotropic properties of the statins have been beneficial in a variety of diseases that involve a number of organs and organ systems. No other therapeutic agent can claim equally stellar results in such a wide variety of diseases. The common denominator in all of the diseases that have been shown to improve with statin pleiotropy could be arteriolar pathology due to hyperlipidemia, which improves in response to statins by a return of arteriolar function to normal rather than through statin pleiotropy. Recent reports indicate that higher doses of statins reverse atheromatous changes in the coronary artery when the LDL cholesterol level is lowered to well below 2.59 mmol/L (100 mg/dL). These results lend additional support to the probability that similar pathological changes that may be present in the small arteries and arterioles also can respond to adequate statin therapy. Statin pleiotropy: fact or fiction?

Prinzmetal's angina.

Prinzmetal's angina, often referred to as "variant" angina, is a temporary increase in coronary vascular tone (vasospasm) causing a marked, but transient reduction in luminal diameter. This coronary vasospastic state is usually focal at a single site and can occur in either a normal or diseased vessel. Patients are predominantly younger women who may not have the classical cardiovascular risk factors (except for cigarette use). PVA has been associated with vasospastic disorders such as Raynaud's phenomenon and migraine headaches. Arrhythmias are common and may be life threatening especially when the effects of vasospasm are seen in those ECG leads that reflect the potential variations of the epicardial surface of the left ventricle. Endothelial dysfunction has been considered as primarily responsible for PVA. The diagnosis is made by observing transient ST-segment elevation during the attack of angina. Since PVA is not a "demand"- induced symptom, but rather a supply (vasospastic) abnormality, exercise treadmill stress testing is of no value in the diagnosis of PVA. The most sensitive and specific test for PVA is the administration of ergonovine intravenously. Fifty micrograms at 5-minute intervals is given until a positive result or a maximum dose of 400 microg has been administered. When positive, the symptoms and associated ST-segment elevation should be present. Nitroglycerin rapidly reverses the effects of ergonovine if refractory spasm occurs. Medical therapy classically employs vasodilator drugs, which include nitrates and calcium channel blockers. The prognosis is good when there is no significant coronary artery stenosis. Treatment of associated coronary atherosclerosis in elderly patients with PVA is advised. When PVA is associated with coronary atherosclerosis, the prognosis is determined by the severity of the underlying disease. beta-Blockers and large doses of aspirin are contraindicated in PVA.

Focus: hypertension in the aged population.

The treatment of the elderly hypertensive patients has reduced the incidence of strokes, cardiovascular events, and cardiovascular morbidity. Regrettably, few hypertensive patients over 80 years of age are being treated, and those who are, are not being treated effectively. Hypertension, at any age, should be treated with a goal of BP <140/90 mmHg, as set by the Joint National Committee on Hypertension. This message should be spread throughout the medical community.

Novel markers in the acute coronary syndrome: BNP, IL-6, PAPP-A.

Most patients (about 85%) seen in the ED to rule out an acute coronary event do not have acute coronary disease. In addition, the presenting ECG findings have been nondiagnostic in 50% of patients with acute MI. Our current knowledge of atherosclerosis as being a chronic low-grade inflammatory process triggered the search for reliable serum markers that have improved the diagnostic accuracy management and prognosis of this prevalent disease. Newer and potential inflammatory markers currently under investigation deserve watching in future reports. These among others include those markers produced by the arterial wall itself, that is, cell adhesion molecules (CAM), inter-cellular adhesion molecules (ICAM), and vascular adhesion molecules (VCAM). The expression of CAM is a marker of dysfunctional endothelial cells. It is likely that more cardiac markers will be reported in the future. Time will tell.

A silent killer--often preventable.

Deep vein thrombosis and its potentially fatal complication, PE, accounts for more than 250,000 hospitalizations annually in the United States. Pulmonary embolism is the most serious complication and has a 3-month mortality of 17%. Two million people each year are affected by VTE, and the prevalence is rising because of the aging population. Deep vein thrombosis and its potential complication, PE, is preventable. However, there still is widespread failure to screen, diagnose, and initiate prophylactic therapy in patients at risk. This failure can be corrected by development of a heightened awareness of risk factors among emergency department physicians and nurses and by similar personnel caring for bedridden hospitalized patients. A recent landmark study Prophylaxis in Medical Patients With Enoxaparin Study (MEDENOX) revealed the risk factors of VTE in order of frequency: (1) previous VTE, (2) acute infectious disease, (3) cancer, (4) age greater than 75 years, and (5) chronic respiratory disease. This study confirmed the effectiveness of a LMWH, enoxaparin, in the prevention of VTE.

The effects of aging on arteries.

The age association and alterations in vascular structure and function at both the cellular and molecular levels are increasingly recognized as major risk factors for CV disease. The arterial remodeling during aging that may be enhanced by the CV risk factors are supersensitive to the age-related risk factors. The aging process may well be influenced by a combination of hereditary and environmental factors. Much can be done to modify environmental risk factors, very little to genetics except for choosing your parents.

High-sensitivity C-reactive protein is the most effective prognostic measurement of acute coronary events.

Inflammation plays a major role in the pathogenesis of arterial atherosclerosis. The stages of atheroma development from early recruitment of leukocytes and fatty streaks to the unstable plaque and finally rupture are mediated by the inflammatory process. Several markers of vascular wall inflammation that can predict future risk of plaque rupture have been identified. However, these lack the specificity of CRP. Numerous large-scale prospective studies established hs-CRP as a strong biochemical marker for the prediction of future first or recurrent coronary events. A Food and Drug Administration-approved method for measuring hs-CRP is currently available.

Retirement is no excuse for physical inactivity or isolation.

At all age levels and especially in the elderly population, a sedentary lifestyle and low fitness levels are independent risk factors for all causes of mortality, including cardiovascular mortality. Exercise improves cardiovascular outcomes by increasing vagal activity and attenuating sympathetic hyperactivity. The risk of diabetes mellitus type 2 developing is reduced by 40% in men of normal weight and 60% in overweight men when on a regular exercise program. Physical activity in the elderly sustains cerebral perfusion, maintaining cognitive function. Isolation, which is not uncommon among the elderly, fosters cognitive decline. Stimulating mental activity can protect against dementia.

Peripheral arterial disease is only the tip of the atherosclerotic "iceberg".

The peripheral vascular system makes up the largest single "organ system" and holds many biological secrets that, when unlocked, can open doors for new treatments for all vascular beds, including those of the coronary and cerebral arteries. The coronary and noncoronary circulations are inseparable and interdependent. Cardiologists as well as primary care physicians should have a global view in the management of patients with PAD. The treatment of atherosclerosis in any of the arterial beds is a multifactorial problem. PAD is underrecognized. Antiplatelet and lipid-lowering therapy is underutilized in patients with PAD. Clopidogrel, an antiplatelet drug, has proven to prevent adverse cardiovascular events in patients with PAD. Therapeutic angiogenesis has been reported to improve severe claudication.