BackgroundDuchenne muscular dystrophy (DMD) is frequently complicated by development of a cardiomyopathy. Despite significant medical advances provided to DMD patients over the past 2 decades, there remains a group of DMD patients who die prematurely. The current study sought to identify a set of prognostic factors that portend a worse outcome among adult DMD patients.Methods and ResultsA retrospective cohort of 43 consecutive patients was followed in the adult UT Southwestern Neuromuscular Cardiomyopathy Clinic. Clinical data were abstracted from the electronic medical record to generate baseline characteristics. The population was stratified by survival to time of analysis and compared with characteristics associated with death. The DMD population was in the early 20s, with median follow‐up times over 2 years. All the patients had developed a cardiomyopathy, with the majority of the patients on angiotensin‐converting enzyme inhibitors (86%) and steroids (56%), but few other guideline‐directed heart failure medications. Comparison between the nonsurviving and surviving cohorts found several poor prognostic factors, including lower body mass index (17.3 [14.8–19.3] versus 25.8 [20.8–29.1] kg/m2, P<0.01), alanine aminotransferase levels (26 [18–42] versus 53 [37–81] units/L, P=0.001), maximum inspiratory pressures (13 [0–30] versus 33 [25–40] cmH2O, P=0.03), and elevated cardiac biomarkers (N‐terminal pro‐brain natriuretic peptide: 288 [72–1632] versus 35 [21–135] pg/mL, P=0.03].ConclusionsThe findings demonstrate a DMD population with a high burden of cardiomyopathy. The nonsurviving cohort was comparatively underweight, and had worse respiratory profiles and elevated cardiac biomarkers. Collectively, these factors highlight a high‐risk cardiovascular population with a worse prognosis.
Low high-density lipoprotein cholesterol (HDL-C) levels are associated with incident cardiovascular events; however, many therapies targeting increases in HDL-C have failed to show consistent clinical benefit. Thus, focus has recently shifted toward measuring high-density lipoprotein (HDL) function. HDL is the key mediator of reverse cholesterol transport, the process of cholesterol extraction from foam cells, and eventual excretion into the biliary system. Cholesterol efflux from peripheral macrophages to HDL particles has been associated with atherosclerosis in both animals and humans. We review the mechanism of cholesterol efflux and the emerging evidence on the association between cholesterol efflux capacity and cardiovascular disease in human studies. We also focus on the completed and ongoing trials of novel therapies targeting different aspects of HDL cholesterol efflux.
Objective While recent genomic studies have focused attention on triglyceride (TG) rich lipoproteins in cardiovascular disease (CVD), little is known of very low-density lipoprotein cholesterol (VLDL-C) relationship with atherosclerosis and CVD. We examined, in a high-risk type-2 diabetic population, the association of plasma VLDL-C with coronary artery calcification (CAC). Methods The Penn Diabetes Heart Study (PDHS) is a cross-sectional study of CVD risk factors in type-2 diabetics (n=2118, mean age 59.1 years, 36.5% female, 34.1% Black). Plasma lipids including VLDL-C were calculated (n=1879) after ultracentrifugation. Results In Tobit regression, VLDL-C levels were positively associated with increasing CAC after adjusting for age, race, gender, Framingham risk score, body mass index, C-reactive protein, exercise, medication and alcohol use, hemoglobin A1c, and diabetes duration [Tobit ratio (TR) and 95% confidence interval (CI) 0.38 (0.12–0.65), P=0.005] and even after inclusion of apolipoprotein B data [TR 0.31 (0.03–0.58), P=0.030]. Approximately 3-fold stronger effect was observed in women [TR 0.75 (0.16 – 1.34), P=0.013] than men [TR 0.20 (−0.10–0.50), P=0.189; gender interaction P=0.034]. Plasma VLDL-C was related more strongly to CAC scores than TG levels (e.g., Akaike information criteria of 7263.65 v. 7263.94) and had stronger CAC association in individuals with TGs >150mg/dl (TR 0.80, P=0.010) vs. those with TGs <150 mg/dl (TR 0.27, P=0.185). Conclusions In PDHS, VLDL-C is associated with CAC independent of established CVD risk factors, particularly in women, and may have value even beyond apolipoprotein B levels and in patients with elevated TGs.
Purpose of Review Recognition of subclinical myocardial dysfunction offers clinicians and patients an opportunity for early intervention and prevention of symptomatic cardiovascular disease. We review the data on novel biomarkers in subclinical heart disease in the general population with a focus on pathophysiology, recent observational or trial data, and potential applicability and pitfalls for clinical use. Recent Findings High-sensitivity cardiac troponin and natriuretic peptide assays are powerful markers of subclinical cardiac disease. Elevated levels of these biomarkers signify subclinical cardiac injury and hemodynamic stress and portend an adverse prognosis. Novel biomarkers of myocardial inflammation, fibrosis, and abnormal contraction are gaining momentum as predictors for incident heart failure, providing new insight into pathophysiologic mechanisms of cardiac disease. Summary There has been exciting growth in both traditional and novel biomarkers of subclinical cardiac injury in recent years. Many biomarkers have demonstrated associations with relevant cardiovascular outcomes and may enhance the diagnostic and prognostic power of more conventional biomarkers. However, their use in “prime time” to identify patients with or at risk for subclinical cardiac dysfunction in the general population remains an open question. Strategic investigation into their clinical applicability in the context of clinical trials remains an area of ongoing investigation.
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