Hyperuricaemia modulates HDL-C-induced cardiovascular mortality in women

Women with very high levels of high-density lipoprotein cholesterol (HDL-C) are at heightened risk of cardiovascular mortality, with the association following a J-shaped pattern, as reported in a study. Of note, the risk of cardiovascular mortality increases with concomitant hyperuricaemia.

Researchers looked at 18,072 participants from the multicentre URRAH study to examine the association between very high HDL-C levels and cardiovascular mortality and whether this is modulated by hyperuricaemia. Multivariable Cox models were used in the analyses, with stratification by sex and HDL-C category.

A total of 1,307 cases of cardiovascular mortality were recorded over a median follow-up of 11.4 years. Analyses revealed a J-shaped association between cardiovascular mortality and HDL-C levels in the whole population, such that the highest risk was observed in the high HDL-C group (>80 mg/dL; adjusted hazard ratio [HR], 1.28, 95 percent confidence interval [CI], 1.02–1.61; p=0.031).

On further analysis, the increased cardiovascular mortality risk associated with high HDL-C levels was seen only in women (HR, 1.34, 95 percent CI, 1.02–1.77; p=0.034) and not in men.

Moreover, the risk of cardiovascular mortality linked to high HDL-C was markedly greater in women with high uric acid (>0.30 mmol/L; HR, 1.61, 95 percent CI, 1.08–2.39) than in those with low uric acid (HR, 1.17, 95 percent CI, 0.80–1.72; p=0.016 for interaction), as well as in women aged >70 years with hyperuricaemia (HR, 1.83, 95 percent CI, 1.19–2.80; p<0.005). The strength of these associations was attenuated following adjustment for body mass index.

The present data suggest that a proinflammatory/oxidative state can aggravate the detrimental cardiovascular effects associated with high HDL-C levels.