Objective Statins, among the most commonly prescribed of medications, are associated with a wide range of musculoskeletal side effects. These include a progressive autoimmune myopathy with anti-HMGCR antibodies that requires immunosuppression. However, it remains unknown whether these antibodies are found in statin users with and without self-limited musculoskeletal side effects; this limits their diagnostic utility. The current work assesses the prevalence of anti-HMGCR antibodies in these groups of statin users. Methods We determined the prevalence of anti-HMGCR antibodies in (a) 1966 participants (including 763 current statin users) in a sub-study of the community-based Atherosclerosis Risk in Communities (ARIC) Study and (b) 98 French Canadian subjects with familial hypercholesterolemia, including 51 with documented statin intolerance. Results No participant in the ARIC sub-study, including those with past or current statin exposure at the time of sample collection, had anti-HMGCR antibodies. Similarly, none of 51 patients with self-limited statin intolerance or 47 statin-tolerant patients on maximal statin therapy were anti-HMGCR positive. Conclusions The vast majority patients with and without statin exposure, including those with self-limited statin intolerance, do not develop anti-HMGCR antibodies. Thus, anti-HMGCR antibodies are highly specific for those with an autoimmune myopathy.

OBJECTIVETo examine the association between diabetes, glycemic control, and risk of fracture-related hospitalization in the Atherosclerosis Risk in Communities (ARIC) Study.RESEARCH DESIGN AND METHODSFracture-related hospitalization was defined using International Classification of Diseases, 9th revision, codes (733.1–733.19, 733.93–733.98, or 800–829). We calculated the incidence rate of fracture-related hospitalization by age and used Cox proportional hazards models to investigate the association of diabetes with risk of fracture after adjustment for demographic, lifestyle, and behavioral risk factors.RESULTSThere were 1,078 incident fracture-related hospitalizations among 15,140 participants during a median of 20 years of follow-up. The overall incidence rate was 4.0 per 1,000 person-years (95% confidence interval [CI], 3.8–4.3). Diagnosed diabetes was significantly and independently associated with an increased risk of fracture (adjusted hazard ratio [HR], 1.74; 95% CI, 1.42–2.14). There also was a significantly increased risk of fracture among persons with diagnosed diabetes who were treated with insulin (HR, 1.87; 95% CI, 1.15–3.05) and among persons with diagnosed diabetes with hemoglobin A1c (HbA1c) ≥8% (1.63; 1.09–2.44) compared with those with HbA1c <8%. Undiagnosed diabetes was not significantly associated with risk of fracture (HR, 1.12; 95% CI, 0.82–1.53).CONCLUSIONSThis study supports recommendations from the American Diabetes Association for assessment of fracture risk and implementation of prevention strategies in persons with type 2 diabetes, particularly those persons with poor glucose control.

We examined the association of plasma lactate at rest, a marker of oxidative capacity, with incident cardiovascular outcomes in 10,006 participants in the Atherosclerosis Risk in Communities (ARIC) Study visit 4 (1996-1998). We used Cox proportional-hazards models to estimate hazard ratios of incident coronary heart disease, stroke, heart failure, and all-cause mortality by quartiles of plasma lactate (Q1, ≤5.3 mg/dL; Q2, 5.4-6.6; Q3, 6.7-8.6; and Q4 ≥8.7). During a median follow-up time of 10.7 years, there were 1,105 coronary heart disease cases, 379 stroke cases, 820 heart failure cases, and 1,408 deaths. A significant graded relation between lactate level and cardiovascular events was observed in the demographically adjusted model (all P for trend < 0.001). After further adjustment for traditional and other potential confounders, the association remained significant for heart failure (Q4 vs. Q1: hazard ratio (HR) = 1.35, 95% confidence interval (CI): 1.07, 1.71) and all-cause mortality (HR = 1.27, 95% CI: 1.07, 1.51) (P for trend < 0.02 for these outcomes) but not for coronary heart disease (HR = 1.02, 95% CI: 0.84, 1.24) and stroke (HR = 1.26, 95% CI: 0.91, 1.75). The results for heart failure were robust across multiple subgroups, after further adjustment for N-terminal pro-B-type natriuretic peptide and after exclusion of participants with incident heart failure within 3 years. The independent associations of plasma lactate with heart failure and all-cause mortality suggest an important role for low resting oxidative capacity.

Among individuals with obesity and insulin resistance syndromes, apolipoproteins did not provide prognostic information regarding CHD risk beyond that provided by non-HDL-C and HDL-C.

No abstract available.