Higher HDL cholesterol levels are associated with increased markers of interstitial myocardial fibrosis in the MultiEthnic Study of Atherosclerosis (MESA)

Emerging research indicates that high HDL-C levels might not be cardioprotective, potentially worsening cardiovascular disease (CVD) outcomes. Yet, there is 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. There were 1863 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 = 1172 and native-T1; N = 1863) and replacement fibrosis by LGE (N = 1172). 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. 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 = 7 ms, 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. 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.