Serum total and high-density lipoprotein phospholipids: independent predictive value for cardiometabolic risk

Given that serum phospholipids (PL) may serve as inflammation mediators, we studied whether they predicted metabolic syndrome (MetS), type-2 diabetes or coronary heart disease (CHD) risk in people prone to enhanced low-grade inflammation.

We analyzed unselected middle-aged Turkish adults with available serum total (n = 852) and HDL-PL (n = 428) measurements and follow-up (mean 6.6 years) by Cox or logistic regression, after exclusion of prevalent cases of outcome disorder. The enzymatic method used measured total content of phosphatidylcholine, sphingomyelin and lyso-phosphatidylcholine.

Most lipid and non-lipid variables were significantly different in the upper two compared with the lowest total PL tertile, whereby apolipoprotein (apo)A-I and HDL-cholesterol were higher (not lower). ApoA-I, HDL-cholesterol and uric acid were uniformly positive independent linear covariates of total and HDL PL, apoA-I even in participants without MetS. After adjustment for sex, age, waist circumference, HDL-cholesterol and systolic blood pressure, logistic regression for incident MetS disclosed a 3-fold risk (RR [95% CI 1.28; 6.81]) in the upper HDL-pl tertile. In Cox regression models, while the combined two higher HDL-pl tertiles significantly protected against CHD risk in males (HR 0.29 [95% CI 0.10; 0.89]), they weakly tended to impart risk in females: upper two total PL tertiles tended to increased risk of diabetes and CHD.

Excess total PL may mediate inflammatory properties to apoA-I, HDL and uric acid. Excess HDL-pl independently predict risk for MetS in each gender, but are protective against CHD risk in men, possibly because oxidized PL content mediated by total PL is sex-dependent, as reviewed elsewhere.