A Pathophysiologic Primary Prevention Review of Aspirin Administration to Prevent Cardiovascular Thrombosis.

OBJECTIVE: Cardiovascular disease is the leading metabolic cause of mortality in the United States. Among current therapies, low-dose aspirin has been shown to reduce cardiovascular thrombosis. However, aspirin also causes major complications (hemorrhagic stroke and gastrointestinal bleeding). The American Heart Association recommends that aspirin only be prescribed for "high-risk" individuals. No guidelines are available as to the duration of aspirin therapy. METHODS: A reasonable approach to aspirin administration is to determine the appropriateness of aspirin therapy based on the pathophysiology of coronary artery thrombosis. It suggests that the coronary artery calcium (CAC) score be used as the basis for determining "high risk." This score was shown to accurately predict future cardiovascular events. The greater the CAC score, the greater the extent of coronary artery atherosclerotic plaque and future cardiovascular risk. RESULTS: A CAC score >400 places an individual at very-high 10-year risk for an atherosclerotic event. Since aggressive medical therapy initiates stabilization of unstable atherosclerotic plaques within 1 month and reversal within 2 years, this treatment significantly reduces the risk of the individual for a cardiovascular event. Thus, most individuals aged <75 years with a CAC score of >400 should receive aspirin therapy for a maximum of 2 years. CONCLUSION: Utilization of a CAC score greatly simplifies the decision of whom to treat with aspirin and for what duration. Importantly, focusing on two factors (hemorrhage and plaque stabilization) is easily understood by both the physician and the patient. ABBREVIATIONS: CAC = coronary artery calcium; CVD = cardiovascular disease; LDL = low-density lipoprotein; OCT = optical coherence tomography.

Cholesterol Review: A Metabolically Important Molecule.

OBJECTIVE: Cholesterol is an important molecule in humans and both its excess and its deficiency cause disease. Most clinicians appreciate its role in stabilizing cellular plasma membranes but are unaware of its myriad other functions. METHODS: This review highlights cholesterol's newly recognized important roles in human physiology and pathophysiology. RESULTS: The basis for cholesterol's ubiquitous presence in eukaryote organisms is its three part structure involving hydrophilic, hydrophobic, and rigid domains. This structure permits cholesterol to regulate multiple cellular processes ranging from membrane fluidity and permeability to gene transcription. Cholesterol not only serves as a molecule of regulation itself, but also forms the backbone of all steroid hormones and vitamin D analogs. Cholesterol is responsible for growth and development throughout life and may be useful as an anticancer facilitator. Because humans have a limited ability to catabolize cholesterol, it readily accumulates in the body when an excess from the diet or a genetic abnormality occurs. This accumulation results in the foremost cause of death and disease (atherosclerosis) in the Western world. Identification of cholesterol's disease-producing capabilities dates back 5,000 years to the Tyrolean iceman and more recently to ancient mummies from many cultures throughout the world. In contrast, a deficiency of cholesterol in the circulation may result in an inability to distribute vitamins K and E to vital organs with serious consequences. CONCLUSION: Understanding the benefits and hazards of cholesterol in the clinical setting will improve the endocrinologist's ability to control diseases associated with this unique molecule. ABBREVIATIONS: CVD = cardiovascular disease; HDL = high-density lipoprotein; LDL = low-density lipoprotein; NPC1L1 = Niemann-Pick C-1-like-1 protein; U.S. = United States; USDA = U.S. Department of Agriculture.

Interpreting the Coronary Artery Calcium Score - Critical Information for the Practicing Physician.

Coronary artery calcium scanning is a routine test for assessing the severity of atherosclerosis in asymptomatic individuals. This inexpensive, noninvasive test quantifies the calcium deposition in the 4 principal coronary arteries. Correct interpretation is important to the physician (for recommending therapy) and to the patient (for determining his or her lifetime risk of a cardiovascular event). A score of 0 indicates that a cardiovascular event is extremely unlikely in the next 5 years. In contrast, a score greater than 0 portends a coronary event. The higher the score, the greater the risk. Both the arterial location of the calcium and the number of coronary arteries involved alter the interpretation of the calcium score. At any given age, females have significantly lower scores than males. One-third of individuals with scores greater than 1000 will have a cardiovascular event within 3 years. For all elevated calcium scores, aggressive treatment is warranted, including significant lifestyle changes and medications to reduce low-density lipoprotein cholesterol. Understanding the importance of the coronary artery calcium score will result in improved therapy and patient compliance.

A Simplified Approach to Reducing Cardiovascular Risk.

CONTEXT: Cardiovascular disease remains the number one cause of morbidity and mortality in the United States, despite major advances in our understanding of its pathogenesis and prevention. One reason for this continued epidemic is the poor adherence to treatment guidelines by caregivers and the lack of understanding by patients relative to its reversibility with treatment. Current guidelines are complex and often contradictory; there are at least 21 organizations publishing guidelines. OBJECTIVE: This article proposes a simplified approach that is based on the low-density lipoprotein (LDL) hypothesis stating that the lower the LDL cholesterol (LDL-C), the less the cardiovascular disease. This goal focuses on obtaining a plasma LDL-C <50 mg/dL. DESIGN: A positive coronary artery calcium scan in conjunction with an intermediate online cardiovascular risk score will identify individuals with substantial cardiovascular disease risk. With lifestyle improvements (including a low cholesterol diet) and low-dose hypolipemic generic oral medications, this LDL-C concentration is readily achievable in the majority of asymptomatic patients at risk for atherosclerosis. CONCLUSION: Controlling the cardiovascular epidemic will require participation of both the patient and the physician caregiver. By simplifying the therapeutic regimen, patient compliance will increase, and an important reduction in cardiovascular morbidity and mortality will follow.

Management of Asymptomatic Patients With Positive Coronary Artery Calcium Scans.

BACKGROUND: The widespread availability of the coronary artery calcium scan to diagnose coronary artery atheroma semiquantitatively and its prognostic significance has frequently resulted in a difficult therapeutic decision for physicians caring for asymptomatic patients. PATIENTS AND RISK FACTORS: Of particular concern are patients over 40 years of age and young adults characterized by multiple cardiovascular risk factors. The correct prognostic interpretation of coronary artery calcium scores and the potential benefits and risks of various therapeutic modalities need to be understood. CONCLUSION: This review describes the therapeutic choices available to endocrinologists and provides recommendations for various treatment options.

The Role of a Coronary Artery Calcium Scan in Type 1 Diabetes.

The coronary artery calcium (CAC) scan has recently emerged as a reproducible noninvasive test to detect asymptomatic atherosclerotic coronary artery disease. It has several advantages over the traditional cardiac stress testing modalities, including lower cost, greater sensitivity for nonobstructing coronary artery lesions, and excellent prognostic value when combined with the Framingham risk parameters. Its chief disadvantage is that it does not identify obstructing coronary artery lesions or noncalcified coronary artery plaque. A CAC scan utilizes a chest computed tomogram and computer software to calculate the amount of calcium in the four main coronary vessels. Calcium is deposited in coronary plaques so that the greater the calcium score, the greater the plaque burden. This, in turn, is the basis for predicting a 10-15-year risk of a cardiovascular event. Individuals with a zero calcium score have a very low 10-year risk of a cardiovascular event. Obtaining a calcium score in a diabetic patient permits rational decisions for prescribing statin therapy. In patients with a zero score, the initiation of statin therapy is not recommended because the 5-year incidence of atherosclerotic cardiovascular disease is so low. In patients with diabetes, it is recommended to repeat the calcium scan in 4-5 years to permit timely therapy in the event that the score becomes positive. Since statins mildly increase coronary calcium as part of the stabilization of plaque, a reduction in the calcium score should not be anticipated. However, progression of the calcium score by more than 15%/year (calculated from a repeat CAC scan) provides additional prognostic information of an indication of progression of atherosclerosis. In summary, the coronary calcium score is a major clinical advance for noninvasively detecting coronary artery disease and managing antiatherosclerotic therapy in type 1 diabetes.