Purpose: Confirmatory factor analysis (CFA) was used to test the hypothesis whether adipocytokines are associated with the risk factor cluster that characterizes the metabolic syndrome (MetS).Methods: Data from 134 nondiabetic subjects were analyzed using CFA. Insulin sensitivity (Si) was quantified using intravenous glucose tolerance tests, visceral fat area by computed tomography and fasting high-density lipoprotein, triglycerides, monocyte chemoattractant protein-1 (MCP-1), serum amyloid A (SAA), tumor necrosis factor (TNF)-alpha, adiponectin, resistin, leptin, interleukin (IL)-6, C-reactive protein (CRP), and plasminogen activator inhibitor (PAI)-1 were measured.Results: The basic model representing the MetS included six indicators comprising obesity, SI, lipids, and hypertension, and demonstrated excellent goodness of fit. Using multivariate analysis, MCP-1, SAA, and TNF-alpha were not independently associated with any of the MetS variables. Adiponectin, resistin, leptin, CRP, and IL-6 were associated with at least one of the risk factors, but when added to the basic model decreased all goodness-of-fit parameters. PAI-1 was associated with all cardiometabolic factors and improved goodness-of-fit compared with the basic model.Conclusions: Addition of PAI-1 increased the CFA model goodness of fit compared with the basic model, suggesting that this protein may represent an added feature of the MetS. Published by Elsevier Inc.

Because cardiovascular disease (CVD) is the most important cause of death in women in the United States, it is imperative that the main risk factors for CVD in women be identified and modified. The risk factors that have the strongest impact on the incidence of CVD in women are not necessarily the same as those for men. The risk for women increases at menopause, most likely because of the decrease in levels of circulating estrogen. The classic risk factor for CVD is altered lipid levels. In middle-aged women, elevated low-density lipoprotein cholesterol levels are somewhat less important relative to lowered levels of high-density lipoprotein cholesterol and elevated triglyceride levels as independent risk factors. The metabolic syndrome, which encompasses a range of conditions known to be CVD risk factors, also has a greater impact on the incidence of CVD in women than in men. Various emerging risk factors appear to be important indicators for vascular disease in women, including C-reactive protein, homocysteine, and lipoprotein(a) levels. Many of these risk factors are affected by hormone replacement therapy, which may diminish CVD risk in postmenopausal women. Because of the complex origin of CVD, it is important to target the full array of risk factors for modification, rather than focusing on a single factor or treatment to the exclusion of other important markers.

Effective January 2010, prior reports of the types listed below were renamed " consensus reports. " EXPERT COMMITTEE REPORTS

JOHN L. KITZMILLER, MD, MS JENNIFER M. BLOCK, BS RN, CDE FLORENCE M. BROWN, MD PATRICK M. CATALANO, MD DEBORAH L. CONWAY, MD DONALD R. COUSTAN, MD ERICA P. GUNDERSON, RD, PHD WILLIAM H. HERMAN, MD, MPH LISA D. HOFFMAN, MSW, LCSW MARIBETH INTURRISI, RN MS CNS, CDE LOIS B. JOVANOVIC, MD SIRI I. KJOS, MD ROBERT H. KNOPP, MD MARTIN N. MONTORO, MD EDWARD S. OGATA, MD PATHMAJA PARAMSOTHY, MD, MS DIANE M. READER, RD, CDE BARAK M. ROSENN, MD ALYCE M. THOMAS, RD M. SUE KIRKMAN, MD

BACKGROUND The rise in LDL with egg feeding in lean insulin-sensitive (LIS) participants is 2- and 3-fold greater than in lean insulin-resistant (LIR) and obese insulin-resistant (OIR) participants, respectively. OBJECTIVE We determined whether differences in cholesterol absorption, synthesis, or both could be responsible for these differences by measuring plasma sterols as indexes of cholesterol absorption and endogenous synthesis. DESIGN Plasma sterols were measured by gas chromatography-mass spectrometry in a random subset of 34 LIS, 37 LIR, and 37 OIR participants defined by the insulin sensitivity index (S(I)) and by BMI criteria selected from a parent group of 197 participants. Cholestanol and plant sterols provide a measure of cholesterol absorption, and lathosterol provides a measure of cholesterol synthesis. RESULTS The mean (±SD) ratio of plasma total absorption biomarker sterols to cholesterol was 4.48 ± 1.74 in LIS, 3.25 ± 1.06 in LIR, and 2.82 ± 1.08 in OIR participants. After adjustment for age and sex, the relations of the absorption sterol-cholesterol ratios were as follows: LIS > OIR (P < 0.001), LIS > LIR (P < 0.001), and LIR > OIR (P = 0.11). Lathosterol-cholesterol ratios were 0.71 ± 0.32 in the LIS participants, 0.95 ± 0.47 in the LIR participants, and 1.29 ± 0.55 in the OIR participants. After adjustment for age and sex, the relations of lathosterol-cholesterol ratios were as follows: LIS < OIR (P < 0.001), LIS < LIR (P = 0.03), and LIR < OIR (P = 0.002). Total sterol concentrations were positively associated with S(I) and negatively associated with obesity, whereas lathosterol correlations were the opposite. CONCLUSIONS Cholesterol absorption was highest in the LIS participants, whereas cholesterol synthesis was highest in the LIR and OIR participants. Therapeutic diets for hyperlipidemia should emphasize low-cholesterol diets in LIS persons and weight loss to improve S(I) and to decrease cholesterol overproduction in LIR and OIR persons.

Background Alterations in protein composition and oxidative damage of high density lipoprotein (HDL) have been proposed to impair the cardioprotective properties of HDL We tested whether relative levels of proteins in HDL2 could be used as biomarkers for coronary artery disease (CAD).Methods: Twenty control and eighteen CAD subjects matched for HDL-cholesterol, age, and sex were studied HDL2 isolated from plasma was digested with trypsin and analyzed by high-resolution matrix-assisted laser desorption Ionization mass spectrometry (MALDI-MS) and pattern recognition analystsResults Partial least squares discriminant analysis (PLS-DA) of mass spectra clearly differentiated CAD from control subjects with area under the receiver operating characteristic curve (ROCAUC) of 0 94 Targeted tandem mass spectrometnc analysts of the model's significant features revealed that HDL2 of CAD subjects contained oxidized methionine residues of apolipoprotein A-I and elevated levels of apolipoprotein C-III A proteomic signature composed of MALDI-MS signals from apoA-I, apoC-III, Lp(a) and apoC-I accurately classified CAD and control subjects (ROCAUC=0 82)Conclusions HDL2 of CAD subjects carries a distinct protein cargo and that protein oxidation helps generate dysfunctional HDL Moreover, models based on selected identified peptides in MALDI-TOF mass spectra of the HDL may have diagnostic potential (C) 2010 Elsevier B V All rights reserved

Objective— To determine whether obesity and insulin resistance associate with changes in the protein content of high-density lipoprotein (HDL) in 2 different groups of men by using targeted proteomics. Methods and Results— Insulin resistance and obesity are hallmarks of type 2 diabetes mellitus and the metabolic syndrome, which confer an increased risk of cardiovascular disease. Recent studies suggest that the protein cargo of HDL makes important contributions to the lipoprotein’s cardioprotective effects. In a discovery study, we used isotope dilution mass spectrometry to quantify the relative concentrations of 5 proteins previously implicated in HDL’s cardioprotective effects in 3 groups of healthy subjects: lean insulin-sensitive, lean insulin-resistant, and obese insulin-resistant individuals. We validated our findings in a different group of subjects. The clusterin concentration in HDL strongly and negatively associated with insulin resistance and body mass index in both populations. HDL clusterin levels were lower in subjects with low HDL and high triglycerides, key components of the metabolic syndrome. There was an inverse correlation between clusterin levels in HDL and very-low-density lipoprotein/low-density lipoprotein. Conclusion— Clusterin levels in HDL are lower in men with reduced insulin sensitivity, higher body mass index, and an unfavorable lipid profile. Our observations raise the possibility that clusterin depletion contributes to the loss of HDL’s cardioprotective properties.

Little is known of the associations of endogenous fatty acids with sudden cardiac arrest (SCA). We investigated the associations of SCA with red blood cell membrane fatty acids that are end products of de novo fatty acid synthesis: myristic acid (14:0), palmitic acid (16:0), palmitoleic acid (16:1 n7), vaccenic acid (18:1 n7), stearic acid (18:0), oleic acid (18:1 n9), and a related fatty acid, cis-7 hexadecenoic acid (16:1 n9). We used data from a population-based case-control study where cases, aged 25 to 74 years, were out-of-hospital SCA patients attended by paramedics in Seattle, WA (n = 265). Controls, matched to cases by age, sex, and calendar year, were randomly identified from the community (n = 415). All participants were free of prior clinically diagnosed heart disease. We observed associations of higher red blood cell membrane levels of 16:0, 16:1n-7, 18:1n-7, and 16:1n-9 with higher risk of SCA. In analyses adjusted for traditional SCA risk factors and trans- and n-3 fatty acids, a 1-SD–higher level of 16:0 was associated with 38% higher risk of SCA (odds ratio, 1.38; 95% confidence interval, 1.12-1.70) and a 1-SD–higher level of 16:1n-9 with 88% higher risk (odds ratio, 1.88; 95% confidence interval, 1.27-2.78). Several fatty acids that are end products of fatty acid synthesis are associated with SCA risk. Further work is needed to investigate if conditions that favor de novo fatty acid synthesis, such as high-carbohydrate/low-fat diets, might also increase the risk of SCA.

Objectives The purpose of this study was to determine the association of combinations of lipid parameters with subclinical atherosclerosis.Background Carotid intima-media thickness (CIMT) and coronary artery calcium (CAC) are significantly associated with incident cardiovascular disease (CVD). The association between common dyslipidemias (combined hyperlipidemia, [simple] hypercholesterolemia, dyslipidemia of metabolic syndrome, isolated low high-density lipoprotein cholesterol, and isolated hypertriglyceridemia) compared with normolipemia, and CIMT and CAC has not been previously examined.Methods The MESA (Multi-Ethnic Study of Atherosclerosis) participants were White, Chinese, African-American, or Hispanic adults without clinical CVD. Subjects with diabetes mellitus or who were receiving lipid-lowering therapy were excluded. Every participant was classified into only 1 of 6 groups defined by specific low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglyceride cut points. Multivariate linear and relative risk regressions evaluated the cross-sectional associations with CIMT and CAC after adjusting for CVD risk factors. Interactions with race, sex, and high-sensitivity C-reactive protein were evaluated for CIMT and CAC outcomes.Results Among 4,792 participants, only those with combined hyperlipidemia and hypercholesterolemia demonstrated both increased common CIMT (combined hyperlipidemia 0.048 mm thicker, 95% confidence interval [CI]: 0.016 to 0.080 mm; hypercholesterolemia 0.048 mm thicker, 95% CI: 0.029 to 0.067 mm) and internal CIMT (combined hyperlipidemia 0.120 mm thicker, 95% CI: 0.032 to 0.208 mm; and hypercholesterolemia 0.161 mm thicker, 95% CI: 0.098 to 0.223 mm) as well as increased risk for prevalent CAC (combined hyperlipidemia relative risk: 1.22, 95% CI: 1.08 to 1.38; hypercholesterolemia relative risk: 1.22, 95% CI: 1.11 to 1.34) compared with normolipemia. The interactions between lipid parameters and race, sex, or high-sensitivity C-reactive protein were not significant for any outcomes.Conclusions Combined hyperlipidemia and simple hypercholesterolemia were associated with increased CIMT and prevalent CAC in a relatively healthy multiethnic population. (J Am Coll Cardiol 2010; 56: 1034-41) (C) 2010 by the American College of Cardiology Foundation

BACKGROUND dyslipidemia is common and is often treated with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins). Little is known about the comparative effectiveness of statins among human immunodeficiency virus (HIV)-infected patients. This study compared the effectiveness and toxicity of statins among HIV-infected patients in clinical care. METHODS we conducted a retrospective cohort study of patients starting their initial statin medications at 2 large HIV clinics (N = 700). The primary observation was change in lipid levels during statin therapy. Secondary observations included whether individualized National Cholesterol Education Program (NCEP) goals for low density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) levels were reached, and toxicity rates. We used linear regression to examine change in lipid levels, controlling for baseline lipid values and demographic and clinical characteristics. We conducted secondary analyses using propensity scores to address confounding by indication. RESULTS the most commonly prescribed statins were atorvastatin (N = 303), pravastatin (N = 280), and rosuvastatin (N = 95). One year after starting a statin therapy, patients who received atorvastatin or rosuvastatin had significantly greater decreases in total cholesterol, LDL-C, and non-HDL-C than patients on pravastatin. The likelihood of reaching NCEP goals for LDL-C levels was higher with the use of rosuvastatin (OR 2.1; P = .03) and atorvastatin (odds ratio [OR], 2.1; P = .001) compared with that of pravastatin. The likelihood of reaching NCEP goals for non-HDL-C levels was higher for rosuvastatin (OR 2.3; P = .045) but not atorvastatin (OR, 1.5; P = .1) compared with pravastatin. Toxicity rates were similar for all 3 statins: 7.3% for atorvastatin, 6.1% for pravastatin, and 5.3% for rosuvastatin. CONCLUSIONS our findings suggest that atorvastatin and rosuvastatin are preferable to pravastatin for treatment of HIV-infected patients with dyslipidemia, due to greater declines in total cholesterol, LDL-C, and non-HDL-C, with similar lower toxicity rates.

Niacin was first discovered to lower cholesterol over 50 years ago, and was demonstrated to reduce major cardiovascular events in 1975 with the report of the Coronary Drug Project. In that study, the use of crystalline niacin reduced myocardial infarction and other cardiovascular events, including the need for cardiovascular surgery. Subsequently, there have been several trials comparing placebo to niacin in combination with bile acid sequestrants or statins that have also shown significant benefit. The cutaneous flushing reaction experienced by most patients when treated with crystalline niacin has been a major impediment in its use. In recent years this drug has had a rebirth and is being used more frequently because of the availability of formulations that are more readily accepted by patients. This Roundtable discussion is meant to give guidance to those who may still have concerns about patient acceptability and who might benefit from the experience of three colleagues who have had an extensive experience in managing lipid disorders with this drug.

We have asked whether the prevalence of combined hyperlipidemia (CHL) differs by race/ethnicity, obesity, and insulin resistance in a contemporary, multiethnic, US cohort. We determined the prevalence and adjusted odds of CHL in a cohort of 5923 men and women free of clinically recognized cardiovascular disease and diabetes according to race/ethnicity (white, Chinese, African American, and Hispanic), obesity, and insulin resistance. Untreated lipid values were imputed for those on lipid-lowering therapy. Combined hyperlipidemia was defined using age- and sex-specific greater than or equal to 75th percentile cut points for low-density lipoprotein cholesterol and triglycerides obtained from a predominantly white North American population study. Compared with whites, adjusted odds ratios for CHL were 0.48 in African Americans (95% confidence interval [CI], 0.30-0.75), 1.33 in Hispanics (95% CI, 0.93-1.91), and 1.06 in Asians (95% CI, 0.62-1.82). Within the entire population, the adjusted odds of CHL were over 2-fold higher in overweight and obese participants compared with normal-weight participants and more than 4-fold higher in quartiles 2 through 4 of insulin resistance compared with quartile 1. African Americans had lower odds for CHL than whites despite higher body mass index and abdominal adiposity. Hispanics had a nonsignificantly higher trend, and Asians had no significantly different odds than whites. Modest increases in weight and insulin resistance were associated with significantly higher odds of CHL in a multiethnic US population. Further research is needed to determine the most efficacious diet, exercise, and drug management to decrease the risk of CHL and coronary heart disease among racial/ethnic groups in the United States.