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Results of the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) showed that therapy with the fibric acid gemfibrozil significantly reduced the incidence of coronary artery disease events in men with known coronary artery disease and a low level of high-density lipoprotein cholesterol (HDL-C). Coronary artery disease event reduction was inversely related to levels of HDL-C achieved with gemfibrozil and, even at relatively low concentrations of HDL-C, coronary artery disease event reduction with gemfibrozil was significantly greater than with placebo. Subjects with a low HDL-C level who were recruited for VA-HIT had a high prevalence of features of the metabolic syndrome with obesity, type 2 diabetes, and hyperinsulinemia. These individuals especially benefited from gemfibrozil, and thus, fibrate therapy may have an increasing role in reducing coronary artery disease risk in a setting of an increasing worldwide prevalence of obesity and diabetes.
Am J Cardiol 2001 Dec 20
PMID:Targeting low high-density lipoprotein cholesterol for therapy: lessons from the Veterans Affairs High-density Lipoprotein Intervention Trial. 1178 26

The inverse relation between coronary artery disease and the concentration of high-density lipoprotein cholesterol (HDL-C) is well established. A low HDL-C concentration is frequently accompanied by the features of the metabolic syndrome found in patients with type 2 diabetes and in individuals who are abdominally obese. Results from 3 independent trials are consistent in showing that fenofibrate is able to increase HDL-C levels across a wide range of dyslipidemic states. The HDL-C-increasing effect of fenofibrate is proportionately greater when baseline levels are low. Comparing results from published trials, the absolute increase in HDL-C produced by fenofibrate is greater than that with statins across all baseline HDL-C levels, and a 40-mg/dL treatment target HDL-C level is more likely to be achieved with fenofibrate therapy. Fenofibrate has favorable pleiotropic effects on several features of the metabolic syndrome, which are likely to explain the clinical benefits of fibrate therapy, beyond an impact on HDL-C levels. The additional reciprocal beneficial effect of fenofibrate in lowering low-density lipoprotein cholesterol (LDL-C) benefits those patients with low HDL-C and moderately increased LDL-C; the American Diabetes Association now recommends fibrate therapy in this case. Another trial, the Diabetes Atherosclerosis Intervention Study (DAIS) has also provided angiographic evidence to show that fenofibrate treatment may slow coronary artery disease progression in type 2 diabetes. Treatment effects on apolipoproteins suggest that not all fibrates affect HDL-C to an equal degree. A trial with fenofibrate focusing on coronary artery disease risk and mortality reduction in patients with type 2 diabetes that is currently under way, the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial is expected to report in 2005.
Am J Cardiol 2001 Dec 20
PMID:Increasing high-density lipoprotein cholesterol: an update on fenofibrate. 1178 28

Type 2 diabetes is increasingly recognized as a major risk factor for coronary heart disease (CHD). The recent Adult Treatment Panel III of the National Cholesterol Education Program makes special mention of diabetes and the metabolic syndrome and proposes a secondary goal of therapy following achievement of the LDL goal, namely non-HDL cholesterol (the sum of VLDL and LDL cholesterol, i.e. total cholesterol-HDL cholesterol). In addition diabetes is recognized as a CHD risk equivalent. Much information is available from subgroup analysis of the major CHD secondary prevention trials of lipid-lowering with regard to the benefits for diabetic patients. However little information is available from clinical trials in primary prevention. Ongoing trials will help fill this gap. Recently the first report of a large lipid-lowering trial addressing coronary atherosclerosis in a specific diabetic population has been published-the Diabetes Atherosclerosis Intervention Study (DAIS). In this study fenofibrate therapy was associated with reduced progression of coronary atherosclerosis assessed by quantitative coronary angiography.
Curr Opin Lipidol 2001 Dec
PMID:Lipid-lowering trials in diabetes. 1180 61

The importance of the obesity-lipid connection has suffered from the traditional reductionism view of science. Excess body weight has rarely been deemed an independent risk factor for coronary heart disease, directing physicians to target therapies towards the risk factors that excess body weight modifies (e.g. raising HDL, lowering blood pressure) instead of targeting the cause. The efforts of Adult Treatment Panel III to define and identify the metabolic syndrome as a secondary target may spur practitioners to revisit the need for weight management in patients with lipid disorders.
Curr Opin Lipidol 2001 Dec
PMID:Connections between obesity and dyslipidaemia. 1180 62

Morbid obesity is a crucial risk factor in the development of type 2 diabetes and is often associated with a metabolic syndrome closely linked to insulin resistance. This case report illustrates the natural history of morbid obesity, starting during the adolescence and ending with an extremely severe type 2 diabetes at the age of 40. Numerous attempts of weight loss with various medical approaches failed and diabetes mellitus rapidly became insulin-requiring in a context of extreme insulin resistance. Finally, the patient was submitted to a gastric bypass which resulted in a drastic weight loss over 50 kg during the year following surgery without any significant side-effects or complications. Type 2 diabetes almost disappeared and the classical markers of insulin resistance were markedly improved. This clinical case clearly demonstrates that successful management of obesity with bariatric surgery can reverse severe type 2 diabetes.
Rev Med Liege 2001 Dec
PMID:[Clinical case of the month. Natural history of morbid obesity: towards insulin-requiring type 2 diabetes and reversal after bariatric surgery]. 1182 33

The lipid triad: hypertriglyceridemia, low HDL, small dense LDL represents a high risk group for excessive cardiovascular morbidity and mortality in type 2 diabetes. In poorly controlled diabetes LDL are increasingly oxydized and glycosylated whereas HDL degradation is accelerated. The high lipid risk in coincidence with the diseases of the metabolic syndrome leads to the conclusion that diabetes today is a cardiovascular disease demanding an aggressive correction of the lipid triad. The benefit of lipid lowering treatment has been proven not only for statins but there is more and more evidence also in favour of fibrates. Fibrates are particularly useful in the treatment of hypertriglyceridemia/low HDL. This also leads to a reduction in small dense LDL. In the case of insufficient correction of LDL a combination with a low dose of a statin is recommended. A definite answer with respect to the benefit/risk ratio of fibrates should be provided by large ongoing studies with these drugs in representative groups of diabetes patients (LDS, TrUMPET, FIELD).
Herz 2001 Dec
PMID:[Hyperlipidemia and fibrates with special reference to diabetes]. 1182 Jan 55

Objectives. To examine the associations between smokeless tobacco use, smoking, cardiovascular risk factors, inflammation and ultrasound-assessed measures of atherosclerosis in the carotid and femoral arteries. Subjects. The study was performed in a population-based sample of clinically healthy men (n = 391) all 58 years old. Exclusion criteria were cardiovascular or other clinically overt diseases or continuous medication with cardiovascular drugs. Methods. The habits of smoking and oral moist snuff use were assessed by questionnaires. C-reactive protein (CRP) was assessed by high sensitive enzyme-linked immunosorbent assay (ELISA). Intima-media thickness (IMT) in the carotid bulb, the common carotid artery and the common femoral artery and plaque occurrence were measured by ultrasound. Results. The use of oral moist snuff was associated with serum triglycerides and waist-hip ratio (WHR), but not with CRP or ultrasound-assessed measures of subclinical atherosclerosis. Smoking, on the other hand, was associated with CRP, the components in the metabolic syndrome and IMT as well as plaques in the carotid and femoral arteries. In comparison to never-smokers the current smokers had higher values of WHR, triglycerides, C-reactive protein and IMT in carotid bulb and femoral artery. Ex-smokers were in general more obese and had a femoral IMT that was in-between that of never-smokers and current smokers. Conclusions. Tobacco smoking, but not oral moist snuff use, was associated with carotid and femoral artery IMT, and increased levels of CRP. Current smoking was also associated with abdominal obesity. Ex-smokers though, are generally more obese. Smoking was also associated with hyperinsulinaemia, dyslipidaemia and high blood pressure, i.e. the metabolic syndrome. The inhaled smoke from the combustion of tobacco seems to be an important aetiological factor in the atherosclerotic process.
J Intern Med 2001 Dec
PMID:Carotid and femoral atherosclerosis, cardiovascular risk factors and C-reactive protein in relation to smokeless tobacco use or smoking in 58-year-old men. 1190 17

C-reactive protein (CRP) is a prototypic marker of inflammation. Numerous prospective studies in healthy volunteers have confirmed that high-sensitivity CRP (hsCRP) predicts cardiovascular events (CVEs), and hsCRP seems additive to an elevated total cholesterol level and a total/high-density lipoprotein cholesterol ratio in men and women in predicting risk. In smokers and people with metabolic syndrome, hsCRP levels are elevated; in elderly people, there seems to be a relationship between hsCRP and CVEs and mortality. Several properties of CRP make it proatherogenic; however; pending further studies, it should be considered as a risk marker. In people with acute coronary syndromes, hsCRP measurement may be valuable. Elevated levels in the highest quantile seem to predict greater mortality and poorer prognosis in patients with unstable angina and myocardial infarction (MI). While hsCRP is a strong independent predictor of risk of future MI, stroke, peripheral arterial disease, and vascular death, the validity of hsCRP as a risk marker needs to be assessed in all populations. Weight loss, statin drugs, aspirin, and high-dose alpha tocopherol therapy could affect hsCRP. It has its greatest validity as an adjunctive measure in the primary prevention of cardiovascular disease.
Am J Clin Pathol 2001 Dec
PMID:Inflammation and atherosclerosis: the value of the high-sensitivity C-reactive protein assay as a risk marker. 1199 95

From Nov. 1 1990 to Dec. 31 2001 4928 applicants (61 % female, 39 % male) were examined, totalling 6580 pre-employment examinations, to decide whether they fulfilled the health requirement criteria for civil servants. Standardised aptitude criteria were used, career-specific requirements taken into account. To exclude with a high probability were any risks of premature disability for service or frequent disorders. In 394 cases (= 5.99 %) the results were negative. This assessment was final in 298 cases (= 4.53 % of all examinations) or was confirmed negative in repeated examinations even after special conditions had been imposed. Main reasons for disqualification were second- and third-degree adipositas with additional risk factors or a metabolic syndrome, chronic cardio-vascular and metabolic diseases requiring permanent treatment, malignant neoplasms or non-fulfilment of the criteria for special careers. The comparatively high rate of disqualification is mainly due to the high average age of the applicants examined (40 % of all applicants were over 40, 13 % were older than 50). Purpose, sensitivity and specifics of such examinations are discussed. Taking into consideration the high rate of civil servants prematurely unfit for work, such pre-employment examinations are regarded as highly justified. Moreover, it is necessary to have clear guidelines, aptitude criteria and examination procedures for individual careers. It is also important to adhere strictly to local responsibility for pre-employment examinations.
 ...
PMID:["Fitness for public service" - results of standardised acceptance examinations]. 1222 15

Cardiovascular complications are frequently encountered in the HIV-infected population. Cardiac care providers should implement appropriate preventive, screening, and therapeutic strategies to maximize survival and quality of life in this increasingly treatable, chronic disease. All HIV-infected individuals should undergo periodic cardiac evaluation, including echocardiography, in order to identify subclinical cardiac dysfunction. Left ventricular (LV) dysfunction can result from, or be exacerbated by, a variety of treatable infectious, endocrine, nutritional, and immunologic disorders. Aggressive diagnosis and treatment of these conditions may lead to improvement or even normalization of myocardial function. Endomyocardial biopsy should be considered to direct etiology-specific therapy. Standard measures for the prevention and treatment of congestive heart failure are recommended for HIV-infected patients. Afterload reduction with angiotensin-converting enzyme inhibitors may be indicated for patients with elevated afterload and preclinical LV dysfunction diagnosed by echocardiogram. However, judicious drug selection and titration are necessary in this cohort of patients with frequent autonomic dysfunction, at risk for a number of potentially lethal drug interactions. Carnitine, selenium, and multivitamin supplementation should be considered, especially in those with wasting or diarrhea syndromes. Monthly intravenous immunoglobulin (IVIG) infusions have been demonstrated to preserve LV parameters in HIV-infected children; ventricular recovery has been documented in some children with recalcitrant HIV-related cardiomyopathy following IVIG infusion. We support the use of immunomodulatory therapy in the pediatric population, and look forward to further study into the efficacy and broader application of this approach. Highly active antiretroviral therapy (HAART) may be associated with dyslipidemia and the metabolic syndrome. This should be treated with dietary and possibly with pharmacologic interventions. Drug interactions need to be considered when instituting pharmacologic therapies. Pericardial effusions are often seen in patients with advanced HIV infection. Asymptomatic effusions are most often nonspecific in nature, related to the proinflammatory milieu found in advanced AIDS. Nonspecific effusions are a marker of advanced disease and do not require exhaustive etiologic evaluation. In contrast, large or symptomatic effusions are often associated with infection or malignancy, and warrant thorough investigation and etiology-specific treatment.
Curr Treat Options Cardiovasc Med 2002 Dec
PMID:Myocardial and Pericardial Disease in HIV. 1240 91


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