Higher HDL Cholesterol Levels Are Associated with Increased Markers of Interstitial Myocardial Fibrosis: Insights from The Multi-Ethnic Study of Atherosclerosis

Abstract Background: Emerging research indicates that high HDL-C levels might not be cardioprotective, potentially worsening cardiovascular disease(CVD)outcomes. Yet, there's no data on HDL-C's association with other CVD risk factors like myocardial fibrosis, a key aspect of cardiac remodeling predicting negative outcomes. We therefore aimed to study the association between HDL-C levels with interstitial myocardial fibrosis (IMF) and myocardial scar measured by CMR T1-mapping and late-gadolinium enhancement(LGE), respectively. Methods: There were 1,863 participants (mean age of 69-years) who had both serum HDL-C measurements and underwent CMR. Analysis was done among those with available indices of interstitial fibrosis (extracellular volume fraction[ECV];N=1,172 and native-T1;N=1,863) and replacement fibrosis by LGE(N=1,172). HDL-C was analyzed as both logarithmically-transformed and categorized into<40(low),40-59(normal),and≥60mg/dL(high). Multivariable linear and logistic regression models were constructed to assess the associations of HDL-C with CMR-obtained measures of IMF, ECV% and native-T1 time, and myocardial scar, respectively. Results: In the fully adjusted model, each 1-SD increment of log HDL-C was associated with a 1% increment in ECV%( p =0.01) and an 18-ms increment in native-T1( p <0.001). When stratified by HDL-C categories, those with high HDL-C(≥60mg/dL) had significantly higher ECV(β=0.5%, p =0.01) and native-T1(β=7ms, p =0.01) compared with those with normal HDL-C levels. Those with low HDL-C were not associated with IMF. Results remained unchanged after excluding individuals with a history of myocardial infarction. Neither increasing levels of HDL-C nor any HDL-C category was associated with the prevalence of myocardial scar. Conclusions: Increasing levels of HDL-C were associated with increased markers of IMF, with those with high levels of HDL-C being linked to subclinical fibrosis in a community-based setting.