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The American College of Cardiology (ACC)/American Heart Association (AHA) guidelines suggest statin therapy for primary prevention in patients with an estimated 10-year atherosclerotic cardiovascular disease risk ≥7.5%1 as calculated by the Pooled Cohorts Equation. We recently demonstrated that only 53% of individuals eligible for statins based on the ≥7.5% risk criterion would have been eligible for a statin randomized control trial (RCT) in which benefit was demonstrated.2 We sought (1) to evaluate whether the recently published HOPE-3 trial (Heart Outcomes Prevention Evaluation)3 improves the evidence base for the ACC/AHA guidelines and (2) to estimate whether HOPE-3 increases the number of individuals eligible for statins in primary prevention beyond those recommended by the ACC/AHA guidelines. Data from the National Health and Nutrition Examination Survey (NHANES) collected between 2005 and 2010 were used to create a sample of 2134 participants representing 71.8 million Americans without atherosclerotic cardiovascular disease who were not currently taking statins. Participants were categorized based on the following criteria: (1) a 10-year risk of ≥7.5% by Pooled Cohorts Equation; (2) an expected absolute risk reduction of ≥2.3% based on Pooled Cohorts Equation risk and individualized relative risk reductions, as previously described2; …

Background— Several studies have shown that fibrinolytic and coagulation abnormalities as well as low-grade inflammation predict cardiovascular disease and type 2 diabetes. We studied in the Insulin Resistance Atherosclerosis Study the relation of incident diabetes to dynamic changes of plasminogen activator inhibitor-1 (PAI-1) and fibrinogen. Methods and Results— After a follow-up of 5.2 years, diabetes developed in 140 (16.6%) of 843 individuals (57% women; mean age [range], 54.7 [40, 69] years) (converters versus nonconverters). Baseline and follow-up levels of PAI-1 and fibrinogen (demographically and smoking adjusted) were higher in converters versus nonconverters (mean [SE]): at baseline, 23.7 ng/mL (1.5) versus 14.5 (0.4) and 286.2 mg/dL (4.8) versus 273.6 (2.1); at follow-up, 45.3 ng/mL (3.2) versus 25.9 (0.8) and 292.0 mg/dL (5.6) versus 275.2 (2.5); all P P I ) or waist, change in PAI-1 remained significantly related to incident diabetes (OR, 1.66 [1.28, 2.15], and 1.64 [1.28, 2.10]; P Conclusions— Progression of PAI-1 levels over time, in addition to high baseline PAI-1 levels, is associated with incident diabetes. PAI-1 levels (but not fibrinogen) further increase with the rising glucose levels and the development of diabetes. These findings extend the current knowledge on the relation of fibrinolysis and coagulation abnormalities to the development of type 2 diabetes.

Background— In addition to predicting cardiovascular disease (CVD) morbidity and mortality, the metabolic syndrome is strongly associated with the development of type 2 diabetes mellitus (DM), itself an important risk factor for CVD. Our objective was to compare the ability of various metabolic syndrome criteria (including those recently proposed by the International Diabetes Federation), markers of insulin resistance (IR) and inflammation, and impaired glucose tolerance (IGT) in the prediction of DM and to determine whether various proposed modifications to the National Cholesterol Education program (NCEP) metabolic syndrome definition improved predictive ability. Methods and Results— We examined 822 subjects in the Insulin Resistance Atherosclerosis Study aged 40 to 69 years who were nondiabetic at baseline. After 5.2 years, 148 individuals had developed DM. IGT, metabolic syndrome definitions, and IR markers all significantly predicted DM, with odds ratios ranging from 3.4 to 5.4 (all P P >0.05). Similarly, although IR and inflammation variables were significantly associated with incident DM when included in multivariate models with NCEP-defined metabolic syndrome (all P P >0.05). Conclusions— The International Diabetes Federation and NCEP metabolic syndrome definitions predicted DM at least as well as the World Health Organization definition, despite not requiring the use of oral glucose tolerance testing or measures of IR or microalbuminuria. Modifications or additions to the NCEP metabolic syndrome definition had limited impact on the prediction of DM.

Background— Subjects with type 2 diabetes have smaller LDL and HDL particles in addition to higher levels of triglycerides and lower HDL cholesterol. Elevated insulin resistance, blood pressure, and dyslipidemia (including small dense LDL) predicted incident diabetes. In the Insulin Resistance Atherosclerosis Study (IRAS) we studied nuclear magnetic resonance (NMR) lipoprotein particle measures in prediabetic individuals, considering potentially modifying covariates, including insulin resistance, as directly measured using a frequently sampled intravenous glucose tolerance test. Methods and Results— Of 830 subjects who were nondiabetic at baseline, 130 (15.7%) developed diabetes after a mean follow-up of 5.2 years. Various lipoprotein abnormalities were found in prediabetic subjects compared with subjects who stayed nondiabetic at follow-up. In logistic regression analyses (demographically adjusted), VLDL particles, large VLDL, LDL particles, small LDL, large HDL, small HDL, VLDL size, LDL size, and HDL size were related to incident diabetes. The relation of VLDL size and small HDL to incident diabetes was independent of waist (odds ratio [OR] [95% CI], 1.43 [1.18 to 1.73] and 1.23 [1.01 to 1.51] for VLDL size and small HDL, respectively) and independent of conventionally (chemically) measured triglycerides and HDL cholesterol (OR [95% CI], 1.45 [1.18 to 1.78] and 1.30 [1.06 to 1.60], respectively). Insulin sensitivity attenuated the relation to incident diabetes of VLDL size (OR [95% CI], 1.25 [1.01 to 1.53]) but not of small HDL particles (OR [95% CI], 1.25 [1.02 to 1.54]). Conclusions— We have shown a range of lipoprotein abnormalities in prediabetic individuals, including compositional changes in HDL and VLDL. These findings extend previous work indicating a proatherogenic state in healthy, nondiabetic subjects who subsequently develop diabetes.

Background— The metabolic syndrome (MetS) as defined by the National Cholesterol Education Panel definition has been proposed as an indicator of cardiovascular disease risk. Both apolipoprotein (apo)B and non-HDL cholesterol (NHDLC) have been proposed as an additional indicator to identify patients at higher risk in MetS patients. Methods and Results— We studied 1522 individuals in the Insulin Resistance Atherosclerosis Study (IRAS) who were 40 to 69 years of age and from 3 ethnic groups. Their anthropometric measures, lipids, apoB, C-reactive protein, fibrinogen, plasminogen activator inhibitor-1, fasting and post-glucose load glucose, and insulin concentrations were measured, and insulin sensitivity was determined by intravenous glucose tolerance test. Differences in risk parameters in individuals with hyper-apoB/normo-NHDLC, and normo-apoB/hyper-NHDLC were compared in all IRAS subjects and again in those with MetS. In both cases, despite anticipated lower LDL cholesterol, the hyper-apoB/normo-NHDLC group had elevated risk indicated by greater waist circumference (both P P P P P Conclusions— In conclusion, apoB is more closely associated with central adiposity, insulin resistance, thrombosis, and inflammation than NHDLC. Our data suggest that apoB is a better candidate risk parameter than NHDLC for identifying a subgroup of individuals with or without MetS with elevated cardiovascular risk.