Large High-Density Lipoprotein Particle Number is Independently Associated with Microvascular Function in Patients With Well-Controlled Low-Density Lipoprotein Concentration: A Vasodilator Stress Magnetic Resonance Perfusion Study

BACKGROUND: Abnormalities in total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides are associated with microvascular dysfunction. Recent studies suggest that lipid subfractions better predict atherogenic burden than a routine lipid panel. We sought to determine, whether lipid subfractions are more strongly associated with microvascular function and subclinical atherosclerosis, than conventional lipid measurements using vasodilator stress cardiovascular magnetic resonance (CMR). METHODS: Twenty-four adults referred for risk stratification from a lipid clinic with low-density lipoprotein cholesterol (LDL-C) <100 mg/dL underwent vasodilator CMR. Time-intensity curves generated from stress and rest perfusion images were used to determine the area under the curve (AUC) for the mid-ventricular slice myocardium and the left ventricular (LV) cavity. Myocardial perfusion reserve index (MPRi) was defined as stress to rest ratio of mid-ventricular myocardium AUC, normalized to LV cavity AUC. Lipid panels that included subfractions of LDL and high-density lipoprotein (HDL) were measured using nuclear magnetic resonance testing. The association between MPRi and lipid parameters was examined using univariate linear regression; lipid components statistically correlated with MPRi (P < .05) were then subjected to multivariate analysis. RESULTS: Univariate regression analysis showed MPRi was associated with HDL-C, triglycerides, large HDL-P, and small LDL-P; no association was found between MPRi and total cholesterol, LDL-C, total LDL-P, or total HDL-P. Using multivariate analysis, large HDL-P was independently associated with MPRi. CONCLUSIONS: In patients with LDL-C <100 mg/dL, large HDL-P is independently associated with CMR-derived myocardial perfusion reserve, a surrogate for microvascular function and subclinical atherosclerosis. Further studies using lipid subfractions to better understand cardiovascular risks are warranted.