Very low high-density lipoprotein-cholesterol and long-term mortality

Background: High-density lipoprotein-cholesterol (HDL-C) has anti-atherogenic, anti-inflammatory, antioxidative, anti-apoptotic, and vasodilatory properties. A U-shaped association between HDL-C and outcome has been described in patients with existing coronary artery disease with both low and high HDL-levels being linked to increased risk.

Purpose: We tested the interaction between HDL-C and HbA1c-levels with long-term mortality in patients with known coronary artery disease.

Methods: The present analysis is based on the longitudinal ECAD registry of consecutive patients undergoing percutaneous coronary intervention at the West German Heart and Vascular Center between 2004 and 2019. HDL-C and HbA1c was quantified at hospital admission using standardized enzymatic methods. The incidence of death due to any cause was evaluated during follow-up. We report frequency of incident mortality in subgroups, stratified by HbA1c and HDL-levels.

Results: Among 4088 patients, mean age was 66.4±11.4 years and 77.5% were men. Mean HDL-C was 46.6 ± 13.9 mg/dL, mean HbA1c was 6.27±1.18 mg/dL. During a median follow-up 2.72 (0.59; 6.08) years, 494 patients (12.1%) died. In patients with HbA1c < 6%, mortality rate decreased with increasing quintile of HDL-Levels (22.3, 8.6, 11.0, 9.1, 6.7% for 1st to 5th quintile, respectively). In contrast, for patients with HbA1c ≥ 7%, both high and low HDL-levels were linked to higher mortality risk (24.8, 17.7, 10.6, 9.30, 18.5% for 1st to 5th quintile, respectively).

Conclusions: In a large longitudinal registry cohort of patients undergoing invasive coronary angiography, high HDL-levels only associate with increased mortality in case of elevated HbA1c. The interaction of different metabolic parameters needs to be taken into account when evaluating individual patient’s risk.