Relation of Isolated Low High-Density Lipoprotein Cholesterol to Mortality and Cardiorespiratory Fitness (from the Henry Ford Exercise Testing Project [FIT Project])

Isolated low high-density lipoprotein cholesterol (HDL-C) is associated with lower fitness and increased mortality. Whether the association between isolated low HDL-C and mortality differs by fitness is uncertain. Patients in the Henry Ford ExercIse Testing Project (FIT Project) completed a physician-referred treadmill stress test and those prescribed lipid-lowering medications or with known cardiovascular disease were excluded. Isolated low HDL-C was defined as HDL-C <40 mg/dl for men and <50 mg/dl for women with low-density lipoprotein cholesterol (LDL-C) and triglycerides <100 mg/dl (n = 688). An optimal lipid panel was defined as HDL-C ≥40 mg/dl for men and ≥50 mg/dl for women with LDL-C and triglycerides <100 mg/dl (n = 2,923). Mortality was ascertained through Social Security Death Index linkage. Patients with isolated low HDL-C had a mean age of 48.9 ± 12.9 years and 62.9% were women. Over a mean follow-up of 10.3 ± 5 years, 12.8% of patients with isolated low HDL-C and 8.7% with optimal lipids died. Compared to individuals with optimal lipids, those with isolated low HDL-C who achieved <6 METs had a lower survival (p = 0.02), whereas there was no mortality difference for those who achieved 6 to 10 METs (p = 0.13) or ≥10 METs (p = 0.66). In adjusted Cox models, the mortality hazard for those with isolated low HDL-C compared with optimal lipids was 1.73 (95% confidence interval [CI] 1.18 to 2.54), 1.90 (95% CI 1.19 to 3.04), and 0.97 (95% CI 0.53 to 1.78) for the METS categories of <6, 6 to 10, and ≥10. In conclusion, individuals with isolated low HDL-C fitness significantly improved risk stratification and only those with lower fitness had an increased totality mortality risk.