HDL function ‘best measure for cardiovascular risk assessment in obese women’
MedWire News: Functional measures of high-density lipoprotein cholesterol may be better markers for cardiovascular risk in obese women than levels of high-density lipoprotein (HDL) cholesterol per se, research suggests.
The US team found that decreased cholesterol efflux is associated with increased nitration of apolipoprotein (apo)A-I in women with a body mass index (BMI) of 30 kg/m2 or more, and is an independent predictor for impaired endothelial function, a biomarker of cardiovascular risk.
"Our findings might be relevant to the pathophysiology of endothelial dysfunction and preclinical atherosclerosis previously reported in obese subjects," remark Richard Cannon and colleagues from the National Institutes of Health in Bethesda, Maryland.
As reported in The American Journal of Cardiology, the team recruited 54 overweight (BMI 25-29.9 kg/m2) or obese (BMI ≥30 kg/m2) women who were enrolled in a worksite wellness program. Brachial artery flow-mediated dilation, as an index of endothelial nitric oxide bioactivity, was assessed in all of the women.
The researchers report that the mean HDL cholesterol level for the cohort was 57 mg/dL (1.48 mmol/L) and was inversely associated with BMI.
Cholesterol efflux, measured using a transfected baby hamster kidney cell line expressing the human adenosine triphosphate-binding cassette transporter 1 (ABCA1), ranged from 8.2% to 22.5% within 18 hours and was positively correlated with brachial artery flow-mediated dilation. This relationship was particularly strong for obese women, note Cannon et al.
Furthermore, women with efflux values less than the median had significantly reduced (approximately 50%) brachial artery flow-mediated dilation compared with those with efflux greater than the median, regardless of whether their HDL cholesterol values were greater or less than the median.
When the researchers quantitated the nitration of tyrosine residues in apoA-I in participants with high and low efflux capacity they found that nitration was significantly greater in obese women with the lowest cholesterol efflux than in overweight women with the greatest cholesterol efflux (0.44 vs 0.38 AU, respectively).
The authors conclude: "The significant associations between efflux and brachial artery flow-mediated dilation in our study suggest that the interactions of HDL from obese subjects with the ABCA1 transporter might have relevance to endothelial function in humans.
"This could possibly be directly through effects on the lipid content of the endothelium or indirectly through macrophages and other cells within the vessel wall - which might be abundant in obese subjects - that would otherwise diminish the nitric oxide bioavailability resulting from increased intravascular oxidant stress."
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By Nikki Withers