Background and Aims: Higher levels of lipoprotein(a) drive increasing risk of atherosclerotic cardiovascular disease (ASCVD) in otherwise healthy individuals regardless of sex and race/ethnicity. This study aimed to evaluate whether this is also true for recurrent ASCVD, and whether LDL cholesterol-lowering therapy possibly mitigates such a relationship. Methods: In US medical claims between 2012 and 2022 for 340 million individuals, 273 770 had diagnosed ASCVD and lipoprotein(a) measured in nmol/L. These women (n = 117 269; 43%) and men (n = 156 501; 57%) included Black (n = 22 451; 8%), Hispanic (n = 24 606; 9%), and White (n = 161 165; 59%) individuals. Results: Lipoprotein(a) levels were higher in women vs men and in Black vs Hispanic and White individuals. During a median follow-up of 5.4 years, 41 687 individuals (15%) experienced recurrent ASCVD. Higher lipoprotein(a) levels were associated with continuously increasing risk of recurrent ASCVD. Compared to individuals with lipoprotein(a) < 15 nmol/L, the adjusted hazard ratios for recurrent ASCVD events were 1.04 (95% confidence interval 1.01–1.07) for 15–79 nmol/L, 1.15 (1.12–1.19) for 80–179 nmol/L, 1.29 (1.25–1.33) for 180–299 nmol/L, and 1.45 (1.39–1.51) for ≥300 nmol/L. Results were similar for individual ASCVD components, and in sex, race/ethnicity, baseline ASCVD, and diabetes subgroups; however, high impact LDL cholesterol-lowering therapy possibly mitigates the deleterious effect of lipoprotein(a) ≥ 180 nmol/L, most pronounced in those on PCSK9 inhibitors. Interaction on recurrent ASCVD events between lipoprotein(a) categories and sex, race/ethnicity, baseline ASCVD, diabetes, and impact of LDL cholesterol-lowering therapy use had P-values of .61, .06, .33, .91, and 2 × 10−8, respectively. Conclusions: In 273 770 individuals with ASCVD, higher lipoprotein(a) levels were associated with continuously increasing risk of recurrent ASCVD events regardless of sex and race/ethnicity that may have been partially mitigated by high impact LDL cholesterol-lowering therapy.

Adults with atherosclerotic cardiovascular disease (ASCVD) have increased risk of recurrent events and need optimized low density lipoprotein-cholesterol (LDL-C) lowering therapy, yet the factors contributing to LDL-C management are not well understood. This cohort study of the national Family Heart Database aims to characterize the current state of LDL-C management in US adults with ASCVD. Adults with ASCVD and ≥1 medication claim yearly and ≥1 LDL-C measure during 2022 or 2023 were included. The lowest LDL-C level reported (20 of 24 months; 13 to 20 months; >0 to <13 months; none) were characterized. The database included adults (n = 3,593,954) with ASCVD, mean age 67 years, 48 % women, 11 % Black individuals, and 7 % aged <50 years. Of these, 41 % had an LDL-C < 70 mg/dL, 41 % received high intensity LDL-C therapy (statin and nonstatin), and 35 % were dispensed LDL-C therapy for >20 of 24 months; only 13 % were found to have LDL-C management across all three of these components. According to multivariable logistic regression models, women, Black individuals, those <50 years old, and those with peripheral arterial and cerebrovascular disease were less well managed. In this cohort of 3.6 million US adults with ASCVD there was a substantial gap between guideline recommended LDL-C management and clinical care. Several factors contributed to this gap including low use of nonstatin LDL-C therapies in this high-risk population.

Lipoprotein(a) (Lp[a]), is a significant risk factor for cardiovascular disease, yet is infrequently measured. A qualitative investigation was designed to better understand the barriers and facilitators to Lp(a) testing. Focus groups were held with clinicians (n = 26) and at-risk individuals (n = 24). Transcripts were thematically analyzed, guided by the Integrated Screening Action Model (I-SAM). Consistent with the I-SAM, barriers and facilitators of Lp(a) measurement were categorized as motivational, capability, and opportunity factors. Facilitators identified included perceived clinical utility, emotional reassurance associated with a newfound understanding of prior events, the ability to use Lp(a) knowledge to better prepare for the future, as well as active requests for testing. Barriers identified included a lack of perceived clinical utility and the potential to cause emotional distress with results, uncertainty and knowledge limitations around Lp(a), cost-related concerns, low expectations for testing, and clinician reluctance to test. This analysis highlights that Lp(a) testing decisions are multifactorial, providing multiple opportunities for intervention and improvement. Strategies to convey how Lp(a) measurement can inform risk assessment and treatment approaches may be foundational to encouraging more widespread testing.