Is Isolated Low High-Density Lipoprotein Cholesterol a Cardiovascular Disease Risk Factor?

Abstract

Background While the inverse association between high-density lipoprotein cholesterol (HDL-C) and risk of (CVD) has been long established, it remains unclear whether low HDL-C remains a CVD risk factor when levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) are not elevated. This is a timely issue because recent studies have questioned whether HDL-C is truly an independent predictor of CVD. Methods and Results 3590 men and women from the Framingham Heart Study offspring cohort without known CVD were followed between 1987 and 2011. Low HDL-C (<40 mg/dL in men and <50 mg/dL in women) was defined as “isolated” if TG and LDL-C were both low (<100 mg/dL). We also examined higher thresholds for TG (150 mg/dL) and LDL-C (130 mg/dL) and compared low versus high HDL-C phenotypes using logistic regression analysis to assess association with CVD. Compared to isolated low HDL-C, CVD risks were higher when low HDL-C was accompanied by LDL-C ≥100 mg/dL and TG <100 mg/dL (OR 1.3 [1.0, 1.6]), TG ≥100 mg/dL and LDL-C <100 mg/dL (OR 1.3 [1.1, 1.5]), or TG and LDL-C ≥ 100 mg/dL (OR 1.6, [1.2, 2.2]), after adjustment for covariates. When low HDL-C was analyzed with higher thresholds for TG (≥150 mg/dL) and/or LDL-C (≥130 mg/dL) results were essentially the same. In contrast, compared to isolated low HDL-C, high HDL-C was associated with 20-40% lower CVD risk except when TG and LDL-C were elevated. Conclusions CVD risk as a function of HDL-C phenotypes is modulated by other components of the lipid panel.

Sex difference between target levels of cholesterol-related parameters and post-PCI long-term clinical outcomes: From the FU-Registry

“…Definite reason is unclear, but coronary lesion in females is likely to be affected by dyslipidemia. In addition, this study also indicated that the combination of LDL-C and HDL-C is more useful than HDL-C alone for predicting the development of MACEs in females, consistent with the results of the Framingham Heart Study [24] that comprehensive assessment using multiple parameters including HDL-C was important for managing the risk of CAD. Although it is ideal in theory for both LDL-C and HDL-C to have reached their respective target control levels by the time of PCI in both males and females, the incidence of MACEs in females was lower when either LDL-C or HDL-C reached its target level than when neither did so.…”

Prevalence of polymorphisms in the ANKK1, DRD2, DRD3 genes and metabolic syndrome in refractory schizophrenia

“…Low HDL levels predict increased cardiovascular risk, while high HDL levels are associated with a drop of up to 40% in cardiovascular risk compared to low HDL alone; that is to say, when HDL levels are below the recommended levels, there is risk of complications, especially of cardiac nature 21 - 22 .…”

Genetic Basis for Sex Differences in Obesity and Lipid Metabolism

“…However, the reality is more complex than this. Recent work indicates that the context in which HDL levels occur ( i.e ., levels of LDL and triglycerides) influences the utility of HDL as a predictor of cardiovascular disease risk (9). Furthermore, specific subspecies of each of the lipoprotein classes appear to be more relevant to cardiovascular disease prediction than others.…”