In vitro studies have demonstrated that high density lipoprotein particles (HDL-P) antagonize inflammatory processes. We studied the predictive value of HDL-P and inflammatory markers for incident cardiovascular disease (CVD) and non-CVD, non-cancer, chronic inflammatory-related events.
Methods:
In the Multi-Ethnic Study of Atherosclerosis, we studied 6475 men and women free of overt CVD, baseline age 45-84 years, who had fasting venous samples for lipid profile, lipoprotein particles, and inflammatory markers Interleukin-6 (IL-6), hs-CRP and D-dimer at baseline. Median follow-up was 10.1 years. Poisson regression models predicted non-CVD, non-cancer, chronic inflammatory-related events (death and hospitalization), based on diagnostic codes, n=1054) and CVD events due to coronary heart disease, myocardial infarction, coronary artery disease requiring revascularization, stroke, peripheral arterial disease, congestive heart failure and CVD or unwitnessed death (adjudicated, n=756). Adjustment was for age, race, gender, clinic, heart rate, smoking, body mass index, blood pressure, blood pressure and lipid lowering medication, diabetes mellitus, plus all lipid, lipoprotein particle and inflammatory variables.
Results:
Non-CVD, non-cancer, chronic inflammatory-related events were inversely associated with the sum of small+medium HDL-P independent of covariates (relative risk (RR) per standard deviation (95% confidence limits), RR: 0.85 (0.79-0.91, P < 0.0001). Non-CVD, non-cancer, chronic inflammatory-related events were positively associated with IL-6, RR:1.19 (1.11-1.27, P < 0.0001) and D-dimer, RR: 1.10 (1.05-1.16, P < 0.0001). CVD was associated with small+medium HDL-P, RR: 0.90 (0.82-0.99, P < 0.03) and IL-6, RR:1.15 (1.06-1.25 P < 0.0001). hsCRP was unrelated to either outcome after adjustment for other inflammatory markers.
Conclusion:
The long-term inverse association of small+medium HDL-P with non-CVD, non-cancer, chronic inflammatory-related death and hospitalization was stronger than with fatal and non-fatal CVD in subjects initially free of overt CVD. These findings provide clinical evidence that small+medium HDL-P have anti-inflammatory properties and may rethink the importance of HDL-P beyond CVD.
Pregnancy is accompanied by larger high density lipoprotein particles and compositionally distinct subspecies
