Sex-Specific U-Shaped Relationships Between High-Density Lipoprotein Cholesterol Levels and 10-year Major Adverse Cardiovascular Events: A Nationwide Cohort Study of 5.7 Million South Koreans

Abstract

Background: High-density lipoprotein cholesterol (HDL-C) is a well-known predictor of atherosclerotic cardiovascular diseases (ASCVD). We explored the relationships between HDL-C levels and 10-year major adverse cardiovascular events (MACE) and provided sexspecific upper reference limits for HDL-C levels. Methods: Based on the Korean National Health Insurance Sharing Service, we identified 5,703,897 subjects (women, 48%) with age ≥ 40 years, eligible HDL-C results, and no prior ASCVD in 2009. We investigated the distribution of 10-year MACE according to HDL-C levels in 10 mg/dL (0.26 mmol/L) intervals and in three HDL-C groups (low: men < 40 mg/dL [1.03 mmol/L], women < 50 mg/dL [1.29 mmol/L]; high: between low and extremely high levels; and extremely high: > 90 mg/dL [2.33 mmol/L]).Results: There were U-shaped relationships between HDL-C levels and 10-year MACE with later inflection in women than in men (nadir: 80-99 mg/dL [2.07-2.56 mmol/L] and 50-59 mg/dL [1.29-1.53 mmol/L], respectively). In men, the extremely high HDL-C group showed significantly higher 10-year MACE than the high group (28.1% vs. 24.6%, P < 0.0001). In women, the extremely high group showed the lowest 10-year MACE; if the extremely high starting point was raised to 130 mg/dL, it became similar to that in men and showed higher 10-year MACE than the high group (25.6% vs. 20.1%, P < 0.0001). Conclusions:The 10-year MACE showed U-shaped relationships with HDL-C levels, and extremely high HDL-C level at 90 mg/dL (2.33 mmol/L) in men was corresponding in risk to 130 mg/dL (3.36 mmol/L) in women.

High density lipoprotein: When to rethink too much of a good thing

“…These values, however, do not adequately account for the role gender and race play in the development of CVD when HDL-C is extremely elevated. A retrospective study showed that HDL-C>90 mg/dL among males had an increased 10 year associated risk of major adverse cardiac events, whereas women had a similar risk at HDL-C >130 mg/dL [21] . Variability in HDL-C amongst race and ethnic groups have been identified, but their implications are unknown.…”

Apolipoprotein B, Non-HDL Cholesterol, and LDL Cholesterol as Markers for Atherosclerotic Cardiovascular Disease Risk Assessment

“…The Apo B level can be conveniently measured at low cost in routine clinical laboratories and the measurements are more accurate than those of LDL-C or non-HDL-C [6]. Further in-depth study and evaluation are required to validate the recently proposed candidate primary markers for accurate ASCVD risk assessment [12,13]. Continuous efforts to determine the best way for ASCVD risk assessment and treatment target are required.…”

Glycosylation of HDL-Associated Proteins and Its Implications in Cardiovascular Disease Diagnosis, Metabolism and Function

“…One of the problems with HDL particle analysis for diagnostic purposes has been the extreme complexity of these particles and the lack of resolution of older measurement tools. For example, although high HDL-cholesterol (HDL-C) concentrations have been found to be protective against CVD, several large recent studies demonstrated that the relationship between HDL-C concentration and adverse health outcomes tends to follow a U-shaped curve, with both low HDL-C and very high HDL-C being associated with increased cardiovascular (CV) events (21)(22)(23). Clearly, it is not simply the measurement of the total amount of cholesterol carried within HDL that is diagnostic, but rather some other aspect of HDL that is critical, whether it be compositional, structural, or functional.…”