Showing papers by "Scott M. Grundy published in 2014"

Triglyceride–to–High-Density-Lipoprotein-Cholesterol Ratio Is an Index of Heart Disease Mortality and of Incidence of Type 2 Diabetes Mellitus in Men

Abstract: Background High triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) impart risk for heart disease. This study examines the relationships of TG/HDL-C ratio to mortality from all causes, coronary heart disease (CHD), or cardiovascular disease (CVD). Subjects and methods Survival analysis was done in 39,447 men grouped by TG/HDL-C ratio cut point of 3.5 and for metabolic syndrome. National Death Index International Classification of Diseases (ICD-9 and ICD-10) codes were used for CVD and CHD deaths occurring from 1970 to 2008. Incidence of type 2 diabetes mellitus (DM) according to ratio was estimated in 22,215 men. Triglyceride/HDL-C ratio and cross-product of TG and fasting blood glucose (TyG index) were used in analysis. Results Men were followed up for 581,194 person-years. Triglyceride/HDL-C ratio predicted CHD, CVD, and all-cause mortality after adjustment for established risk factors and non-HDL-C. Mortality rates were higher in individuals with a high ratio than in those with a low ratio. Fifty-five percent of men had metabolic syndrome that was also predictive of CHD, CVD, and all-cause mortality. Annual incidence of DM was 2 times higher in men with high TG/HDL-C ratio than in those with a low ratio. Individuals with high TG/HDL-C ratio had a higher incidence of DM than those with a low ratio. The TyG index was not equally predictive of causes of mortality to TG/HDL-C, but both were equally predictive of diabetes incidence. Conclusions Triglyceride/HDL-C ratio predicts CHD and CVD mortality as well as or better than do metabolic syndrome in men. Also, a high ratio predisposes to DM. The TyG index does not predict CHD, CVD, or all-cause mortality equally well, but like TG/HDL-C ratio, it predicts DM incidence.

Prediction of cardiovascular events in statin-treated stable coronary patients of the treating to new targets randomized controlled trial by lipid and non-lipid biomarkers.

Abstract: Several plasma non-lipid biomarkers have been shown to predict major cardiovascular events (MCVEs) in population studies. Our objective was to investigate the relationship between lipid and non-lipid biomarkers levels achieved during statin therapy and the incidence of MCVEs in patients with stable coronary heart disease (CHD). We conducted a substudy of the TNT (Treating to New Targets) study, which was a randomized trial that compared the efficacy of high (80 mg) versus low (10 mg) dose atorvastatin for the secondary prevention of CHD. Fasting plasma levels of standard lipids and of 18 non-lipid biomarkers were obtained after an 8-week run-in period on atorvastatin 10 mg in 157 patients who experienced MCVEs during the 4.9 years of study follow-up and in 1349 controls. MCVE was defined as CHD death, nonfatal, non-procedure-related myocardial infarction, resuscitated cardiac arrest, and fatal or nonfatal stroke. After adjusting for age, sex and treatment arm, plasma levels of high-density lipoprotein (HDL) cholesterol, triglycerides, high-sensitivity C-reactive protein (hsCRP), insulin, neopterin, N-terminal pro-brain natriuretic peptide (BNP), lipoprotein(a) [Lp(a)], and the soluble receptor for advanced glycation end products (sRAGE) were predictive of recurrent MCVEs (P≤0.02 for each doubling of plasma concentration). However, no significant association was observed between the risk of recurrent MCVEs and plasma levels of low-density lipoprotein cholesterol, adiponectin, cystatin C, lipoprotein-associated phospholipase A2, monocyte chemotactic protein-1, matrix metalloproteinase-9, myeloperoxidase, osteopontin, soluble CD40 ligand, soluble intercellular adhesion molecule-1, or soluble vascular cell adhesion molecule-1. After further adjustment for diabetes, hypertension, smoking, and BMI, the relationship between hsCRP, insulin and MCVE were no longer significant, while the relationship between Lp(a), neopterin, NT-proBNP and sRAGE and MCVE remained statistically significant. In conclusion, in patients with CHD treated with atorvastatin, plasma levels of Lp(a), neopterin, NT-proBNP, and sRAGE are associated with the risk of recurrent MCVEs.

Ethnic and Gender Susceptibility to Metabolic Risk

Abstract: Background: Aggregation of metabolic risk factors—i.e., elevated plasma triglyceride (TG), reduced high-density lipoprotein cholesterol (HDL-C), elevated blood pressure, and raised plasma glucose—convey increased risk for atherosclerotic cardiovascular disease and type 2 diabetes. Methods: This study was carried out to determine the association of waist girth, ethnicity, and gender with susceptibility for metabolic risk. Included were 1671 adult women (50.7% black) and 1339 men (46.5% black) enrolled in the Dallas Heart Study. Subjects were stratified into three categories by waist girth—low, intermediate, and high, corresponding to BMI ranges of <25 kg/m2, 25–29.9 kg/m2, and ≥30 kg/m2. Results: Risk factor prevalence rose progressively through each waist-girth category. However, even among those with high waist-girth, prevalence of three or more risk factors was less than 50%. Several differences among the ethnic groups were noted; for example, Hispanic men had a higher prevalence of elevated TG...

Statins: definitive translational research.

Abstract: The development of cholesterollowering statins is one of the highlights of transitional medicine. Statins reduce serum low-density lipoprotein cholesterol (LDL-C) and other atherogenic lipoproteins. Statin use in clinical practice is the outgrowth of extensive research into cholesterol and lipoprotein metabolism, drug discovery and randomized clinical trials (RCTs). Each of these areas is worthy of some review. Cholesterol was first discovered in gallstones. It was named cholesterine by the French chemist Chevreul in 1816. In 1856, Virchow found that lipid (cholesterol) is a key component of atherosclerotic plaques. Subsequently, 13 Nobel Prizes have been awarded to scientists who have studied the structure, chemistry, biochemistry and biology of cholesterol. It has been known for 100 years that high serum cholesterol produces atherosclerosis in animals (1). In the 1940s and 1950s, it was observed that high serum cholesterol consistently associates with premature atherosclerotic disease in humans. Shortly thereafter, cholesterol was discovered to be carried in lipid-protein complexes called lipoproteins (2). Among the lipoproteins, LDL is the predominant atherogenic lipoprotein. LDL from the blood filters into the arterial wall and starts the process of atherogenesis (3). All of the steps whereby LDL initiates atherogenesis and produces cholesterol-rich atherosclerotic plaques are still not fully understood. But importantly, in some individuals, a plaque becomes unstable and undergoes rupture. When this occurs, arterial thrombosis follows and precipitates an acute cardiovascular event (4). Coronary thrombosis and stroke are the major killers accompanying atherosclerosis. The zenith of cholesterol research was the discovery of the LDL receptor by Michael Brown and Joseph Goldstein (5). LDL receptors are located mainly on the surface of liver cells. They recognize the protein component of LDL, known as apolipoprotein B, and remove LDL from the circulation. In a word, LDL receptor expression regulates serum levels of LDL-C. Underexpression leads to hypercholesterolemia; overexpression reduces serum cholesterol levels. LDL receptors also remove some triglyceride-rich lipoproteins but mainly cholesterolenriched LDL. The discovery of the LDL receptor uncovered a potential pathway for markedly lowering levels of serum LDL and preventing atherosclerosis. The mechanisms underlying the regulation of LDL receptor expression have been worked out in exquisite detail by Brown, Goldstein and their colleagues (6). One consequence of the discovery of the LDL receptor was the uncovering of the cause of a condition called familial hypercholesterolemia (FH). In this condition, serum LDL-C levels are elevated from birth and remain elevated throughout life. High LDL-C levels cause the buildup of cholesterol in arteries leading to premature atherosclerotic cardiovascular disease (ASCVD). FH occurs in two forms: heterozygous and homozygous. The former confers half the normal number of LDL receptors; in the latter, receptors are absent. Heterozygous FH patients have twice the normal levels of LDL-C, whereas in homozygous FH levels, LDL-C concentrations are about four Statins: Definitive Translational Research

Statins for all

Abstract: Recent guidelines for cholesterol management proposed by the American College of Cardiology (ACC) and American Heart Association (AHA) recommended statin therapy for most men in their 60s and most women in their 70s. If these guidelines are followed in the United States, most adults will eventually take statins. A companion article in this journal goes a step further by proposing statin initiation for mostly everyone about 10 years earlier. Treatment in ACC/AHA guidelines does not depend on cholesterol levels, for either statin initiation or treatment goals. Selection of patients for statin therapy depends instead on multifactorial risk assessment derived from prospective studies in subgroups of the US population. Because of expansion of statin therapy, the issue of the reliability of risk assessment has come to the fore. Some evidence suggests that the ACC/AHA risk algorithm overestimates risk in many persons; if so, this would lead to statin therapy beyond what was intended. Some investigators favor assessment of risk based on presence or absence of categorical risk factors or higher risk conditions. Others propose selection of individuals for statin therapy grounded in measurement of atherosclerosis burden. Finally, an alternate approach to cholesterol management is to establish cholesterol goals for secondary and primary prevention. Cholesterol levels, and not global risk assessment, here define the intensity of therapy. The use of cholesterol goals allows more flexibility in treatment by taking advantage of lifestyle therapies and various drugs and their doses to attain defined goals.

Impact of the JUPITER trial on statin prescribing for primary prevention.

Abstract: tudy Objective As the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial identified a new population of individuals with cholesterol levels below traditional treatment thresholds but with elevated high-sensitivity C-reactive protein (hs-CRP) levels who may benefit from primary prevention with statin therapy, we sought to evaluate the impact of this trial on the incident prescription rates of rosuvastatin alone as well as all statins in a primary prevention population. Design Population-based, cross-sectional time-series analysis. Data Source Administrative health care databases in Ontario, Canada. Patients A total of 299,809 incident statin users 66 years or older were identified during the study period, from January 1, 2003, to March 31, 2011, who were prescribed statin therapy for primary prevention. Measurements and Main Results We evaluated the incident rate of rosuvastatin and all statin use during each quarter of the study period. Overall, no significant trends in all incident statin use were observed (p=0.99). Furthermore, no significant differences were observed in incident rates of rosuvastatin (p=0.21) or all statin (p=0.41) use after the publication of the JUPITER trial. Despite the lack of impact of the JUPITER trial on rosuvastatin or all statin utilization, the relative market share of rosuvastatin increased from 9% to 65% over the study period. Conclusion The publication of the JUPITER trial did not significantly affect trends in overall statin and rosuvastatin prescribing patterns for primary prevention in this study. Increases in the relative market share of rosuvastatin may be attributed to the impact of the pharmaceutical industry on prescribing patterns. Our results highlight the need to further improve the integration of evidence-based prescribing into cost-effective clinical practice.

the American Heart Association and American College of Cardiology Foundation Coronary and Other Atherosclerotic Vascular Disease: 2011 Update: A Guideline From AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients With

Abstract: Donald M. Lloyd-Jones, Margo Minissian, Lori Mosca, Eric D. Peterson, Ralph L. Sacco, John Barry A. Franklin, Raymond J. Gibbons, Scott M. Grundy, Loren F. Hiratzka, Daniel W. Jones, Sidney C. Smith, Jr, Emelia J. Benjamin, Robert O. Bonow, Lynne T. Braun, Mark A. Creager, the American Heart Association and American College of Cardiology Foundation Coronary and Other Atherosclerotic Vascular Disease: 2011 Update : A Guideline From AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients With Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 2011 American Heart Association, Inc. All rights reserved. is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Circulation doi: 10.1161/CIR.0b013e318235eb4d 2011;124:2458-2473; originally published online November 3, 2011; Circulation. http://circ.ahajournals.org/content/124/22/2458 World Wide Web at: The online version of this article, along with updated information and services, is located on the

[Official document of the International Society of Atherosclerosis: general recommendations for treatment of dyslipidemia. Executive summary].

Abstract: La Sociedad Internacional de Aterosclerosis (IAS) ha actualizado sus recomendaciones para el tratamiento de la hipercolesterolemia y la dislipidemia con el propósito de contribuir a la reducción del riesgo de las enfermedades cardiovasculares (ECV) de origen arteriosclerótico. En este resumen ejecutivo se destacan las principales conclusiones extraídas del amplio informe final, donde se analizan ampliamente los antecedentes del tema, las deliberaciones y los acuerdos alcanzados por los firmantes del documento y se detallan las recomendaciones propuestas por la IAS. Una vez revisadas y criticadas las pruebas documentadas disponibles actualmente, los autores elaboraron una serie de recomendaciones dirigidas a apoyar el juicio clínico, pero no a reemplazarlo. En el informe se han separado las recomendaciones para prevención primaria y secundaria. Para la redacción de esta última se dio prioridad a los resultados de ensayos clínicos aleatorizados (ECA), basándose en las abundantes pruebas y datos que han aportado. En cambio, las recomendaciones para la prevención primaria están basadas en la experiencia acumulada durante muchos años,