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Biomedical subjects

S M Grundy

Publications and source records attributed to S M Grundy.

At least 19 recordsLinked to original sources

Meeting report on the Bellagio Conference 'prevention of vascular diseases in the emerging world: An approach to global health equity'.

Representatives from five international organizations (International Society of Nephrology, World Heart Federation, International Diabetes Federation, International Atherosclerosis Federation, and International Society of Hypertension) participated in a strategic planning workshop in December 2005 in Bellagio, Italy sponsored by the Rockefeller Foundation. There were equal representatives from developed and developing countries. Global perspectives on diabetes and cardiovascular and renal diseases were presented, with special emphasis on China, India, Latin America, and Africa. The rationale and effectiveness of preventive measures were discussed. It was apparent that measures for primary prevention and early intervention for all the chronic vascular diseases are similar. The five organizations agreed that an integrated global approach to chronic vascular diseases is needed. They resolved to collaborate and work towards an integrated approach to chronic vascular diseases with the establishment of a 5-year plan for the prevention and treatment of chronic vascular diseases, including public advocacy, advising international and national agencies, and improving education and the practice of established approaches.

Chronic Disease↗

Serum lipids in the GENECARD study of coronary artery disease identify quantitative trait loci and phenotypic subsets on chromosomes 3q and 5q.

Coronary artery disease (CAD) and dyslipidemia have strong genetic components. Heterogeneity complicates evaluating genetics of complex diseases such as CAD; incorporating disease-related phenotypes may help reduce heterogeneity. We hypothesized that incorporating lipoproteins in a study of CAD would increase the power to map genes, narrow linkage peaks, identify phenotypic subsets, and elucidate the contribution of established risk factors to genetic results. We performed ordered subset analysis (OSA) and quantitative trait linkage (QTL) using serum lipoproteins and microsatellite markers in 346 families with early-onset CAD. OSA defined homogeneous subsets and calculated lod scores across a chromosome after ranking families by mean lipoprotein values. QTL used variance components analysis. We found significantly increased linkage to chromosome 3q13 (LOD 5.10, p = 0.008) in families with higher HDL cholesterol, lower LDL and total cholesterol, lower triglycerides, and fewer CAD risk factors, possibly due to a concentrated non-lipoprotein-related genetic effect. OSA identified linkage on chromosome 5q34 in families with higher cholesterol, possibly representing a hereditary lipoprotein phenotype. Multiple QTLs were identified, with the strongest for: total cholesterol on chromosome 5q14 (LOD 4.3); LDL on 20p12 (LOD 3.97); HDL on 3p14 (LOD 1.65); triglycerides on 18q22 (LOD 1.43); and HDL/TC ratio on 3q27-28 (LOD 2.06). Our findings suggest the presence of etiologic heterogeneity in families with early-onset CAD, potentially due to differential effects of lipoprotein phenotypes. Candidate genes are under investigation.

Adult↗

Metabolic syndrome: therapeutic considerations.

The metabolic syndrome is a constellation of metabolic risk factors for atherosclerotic cardiovascular disease (ASCVD) occurring in one individual. There are five cardiovascular risk factors that accompany the metabolic syndrome: atherogenic dyslipidemia [elevated apolipoprotein B (apo B), elevated triglyceride, small low-density lipoprotein (LDL) particles, and low high-density lipoprotein (HDL)cholesterol], elevated blood pressure, elevated glucose, a prothrombotic state, and a proinflammatory state. The likelihood of an individual developing metabolic syndrome is enhance by underlying risk factors, notably, obesity, insulin resistance, lack of physical activity, advancing age, and hormonal factors (e.g., androgens and corticosteroids). Besides being at higher risk for ASCVD, persons with the metabolic syndrome are at increased risk for type 2 diabetes. Persons with the metabolic syndrome deserve management in the clinical setting to reduce the risk for both ASCVD and type 2 diabetes. The two major therapeutic strategies for treatment of affected persons are modification of the underlying risk factors and separate drug treatment of the particular metabolic risk factors when appropriate. First-line therapy for underlying risk factors is therapeutic lifestyle changes, i.e., weight loss in obese persons, increased physical activity, and anti-atherogenic diet. These changes will improve all of the metabolic risk factors. Whether use of drugs to reduce insulin resistance is effective, safe, and cost-effective before the onset of diabetes awaits the results of more clinical research. Turning to individual risk components, for atherogenic dyslipidemia, drug therapies that promote lowering of apo B and raise HDL cholesterol will be needed for higher risk patients. Treatment of categorical hypertension with drugs has become standard practice. When hyperglycemia reaches the diabetic level, glucose-lowering agents will become necessary when dietary control is no longer effective, and reduction of a prothrombotic state with low-dose aspirin may be indicated in higher-risk patients.

Atherosclerosis↗

United States Cholesterol Guidelines 2001: expanded scope of intensive low-density lipoprotein-lowering therapy.

The new clinical guidelines of the US National Cholesterol Education Program (NCEP) were released in May 2001. These guidelines were published as the NCEP's Adult Treatment Panel (ATP) III report. They are derived from an extensive review of the emerging literature so as to provide an evidence-based report. Thanks to recent clinical trials of cholesterol-lowering therapy, it is possible to expand the scope of clinical management for both dietary and drug therapies. This expansion derives from a conclusive demonstration of efficacy, safety, and cost-effectiveness of therapies. This article will review briefly the major features of ATP III.

Adult↗

Coronary plaque as a replacement for age as a risk factor in global risk assessment.

Risk assessment is assuming an increasing role for identification of high-risk persons for intensive medical intervention to reduce risk for coronary heart disease (CHD). Of particular importance is the need to identify those persons with CHD risk equivalents who can be managed with the same intensity as patients with established CHD. For example, the National Cholesterol Education Program (NCEP) recently classified diabetes as a CHD risk equivalent. The NCEP also recommended use of Framingham risk scoring in persons with multiple (2+) risk factors to uncover others without diabetes who have CHD risk equivalents. One limitation of Framingham risk scoring, however, is that age becomes the dominant risk factor after age 50. Age is a surrogate for coronary atherosclerotic plaque burden, which is the true risk factor. However, for individuals, coronary plaque burden can vary greatly at any given age. For this reason, if coronary plaque burden could be measured accurately with noninvasive techniques, the degree of plaque burden could be used to replace age as a risk factor in Framingham scoring for risk prediction. This article describes a technique whereby such a replacement can be made.

Adult↗

Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels.

BACKGROUND: Prospective studies indicate that baseline levels of C-reactive protein (CRP), the prototypic marker of inflammation, are associated with an increased risk for cardiovascular events. Limited studies have examined therapies that influence high-sensitive CRP (hs-CRP) levels, especially in hyperlipidemic patients. Thus, we tested the effects of 3 hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins), simvastatin (20 mg/d), pravastatin (40 mg/d), and atorvastatin (10 mg/d), on levels of hs-CRP in a randomized, double-blind, crossover trial of 22 patients with combined hyperlipidemia (LDL cholesterol >130 mg/dL and triglycerides of 200 to 600 mg/dL). METHODS AND RESULTS: After 6 weeks of an American Heart Association Step 1 diet, fasting blood samples were drawn at baseline and after 6 weeks of therapy with each drug. hs-CRP levels were significantly decreased after treatment with all 3 statins compared with baseline (median values: baseline, 2.6 mg/L; atorvastatin, 1.7 mg/L; simvastatin, 1.7 mg/L; and pravastatin, 1.9 mg/L; P<0.025). The reductions obtained with the 3 statins were similar. In addition, there was no significant effect on either plasma interleukin-6 or interleukin-6 soluble receptor levels. There was no relationship between reductions in hs-CRP and LDL cholesterol. CONCLUSIONS: Pravastatin, simvastatin, and atorvastatin significantly decreased levels of hs-CRP. These data support an anti-inflammatory effect of these drugs.

Atorvastatin↗

Translation of nutritional sciences into medical education: the Nutrition Academic Award Program.

For the past 40 y the scientific community has decried the inadequacy of the training of physicians and other health professionals in the subject of human nutrition. In 1997 the National Heart, Lung, and Blood Institute developed the Nutrition Academic Award (NAA) Program, an initiative to improve nutrition training across a network of US medical schools. The purpose of this funding, which began in 1998, is to support the development and enhancement of nutrition curricula for medical students, residents, and practicing physicians to learn principles and practice skills in nutrition. The NAA recipients developed the Nutrition Curricular Guide for Training Physicians, a plan to incorporate clinical guidelines into physician practice skills, create educational and assessment practice tools, and evaluate curricula, materials, and teaching tools. Dissemination of NAA activities and materials will be facilitated by a national website, presentations and publications, and consultants and advisors from the NAA nutrition education programs. The NAA Program constitutes a major new effort to enhance nutrition knowledge and skills among health care providers and to effectively apply the science of human nutrition to clinical medicine. This article describes the purpose and aims of the NAA Program, the organizational structure of the network of recipients, a profile of the recipients and individual programs at 21 medical schools, the various strategies to overcome barriers in training physicians in human nutrition, and collaborative and dissemination efforts.

Awards and Prizes↗