Joshi, Parag H.

Introduction: Elevated lipoprotein(a) [Lp(a)] is associated with atherosclerotic cardiovascular disease (ASCVD), yet little is known about Lp(a) testing patterns in real-world practice. We hypothesized that Lp(a) testing occurs in a different population than calculated low density lipoprotein (LDL-C) testing alone, and that elevated Lp(a) is associated with greater lipid-lowering therapy (LLT) initiation and cardiovascular (CV) events. Methods: We used data from 11 health systems participating in the National Patient-Centered Clinical Research Network. We created two cohorts based on lab tests from Jan 1, 2015 to Dec 31, 2019: 1) the Lp(a) cohort, of adults with an Lp(a) test and 2) the LDL-C cohort, of 4:1 date- and site-matched adults with an LDL-C test, but no Lp(a) test. We used logistic regression to assess the relationship between Lp(a) levels (< 50, 50-100, and > 100mg/dL) and initiation of LLT within 3 months; and cox proportional hazards to evaluate Lp(a) levels and time to all-cause hospitalization and the composite of MI, revascularization and ischemic stroke hospitalization. Results: Overall, 20,551 patients (0.06% per year) had Lp(a) tests, with median Lp(a) value 17.5mg/dL (Q1, Q3: 7.0, 56.0). Compared with the LDL-C cohort (N=82,204), the Lp(a) cohort more frequently had ASCVD (24.3% vs. 8.5%) or multiple prior CV events (8.6% vs. 2.6%). Elevated Lp(a) was associated with greater odds of LLT initiation (Figure 1). Elevated Lp(a) was not significantly associated with all-cause hospitalization; however, Lp(a) > 100mg/dL was correlated with composite CV hospitalization compared with Lp(a) < 50mg/dL [adj HR (95% CI): 1.24 (1.06-1.44), p=0.006]. Conclusions: Lp(a) testing occurs more often in adults with ASCVD and multiple CV events, but testing is infrequent. Elevated Lp(a) was associated with LLT initiation, including niacin, despite lack of evidence of CV benefit. There was an association between elevated Lp(a) and CV hospitalization outcomes.

Introduction: Big data techniques offer a novel opportunity to characterize individuals with extreme phenotypes. In this context, we aimed to describe the prevalence of classical Fredrickson-Levy dyslipidemia phenotypes at the extremes of HDL-C levels in a cross-sectional big data study. Methods: We examined 848,801 U.S. adults and children from the Very Large Database of Lipids 1.0 who were referred for lipoprotein testing from 2009 to 2011. We categorized patients into HDL-C percentile categories (<0.1th, 0.1th to 99th to 99.9th, and >99.9th). We examined the prevalence of Fredrickson-Levy dyslipidemia phenotypes (I, IIa, IIb, III, IV and V) within these categories. We identified those who did not meet criteria for any classical dyslipidemia phenotype as the continuum group. Results: Type I and V were mostly present at extremely low HDL-C levels. Type IIa was more prevalent in high vs. low HDL-C levels. Type III was 2-fold more prevalent in extremely low vs. high HDL-C levels. Type IV was the most prevalent classical dyslipidemia phenotype in our population, and was the most frequent at low HDL-C percentiles. About 50% of the extremely low and 90% of the extremely high HDL-C levels were classified into the continuum group. Conclusion: In our cross-sectional big data analysis, there was a significantly higher prevalence of most classical dyslipidemia phenotypes at extremely low HDL-C compared with extremely high HDL-C levels. Only types I and V were more prevalent in extreme groups than general population. To some extent, very low HDL-C levels may be determined by inheritable, highly atherogenic dyslipidemias.