Abstract
Introduction: Higher Lipoprotein(a) (Lp(a)) levels are known to be associated with increased risk of ASCVD. However, the effect of elevated Lp(a) on other cardiovascular (CV) diseases is largely unknown. We sought to identify whether Lp(a) level might be a risk factor for non-atherosclerotic CV conditions. Methods: Using data from the Healthy Nevada Project (HNP), a population genetic study based in Northern Nevada with >52,000 participants, we conducted a retrospective analysis of all participants with recorded Lp(a) levels. An exploratory analysis was performed examining associations between elevated Lp(a) levels and various CV conditions based on ICD 10 codes. Elevated Lp(a) was defined as >50 mg/dl or >125 nmol/L. We examined ICD 10 codes related to venous thromboembolic (VTE) disease and non-rheumatic valvular heart disease (VHD). A Fisher’s Exact Test was performed to assess the significance of these associations. Results: Out of 4,010 HNP participants (age: 62±30; 42.7% female) with an Lp(a) result, 881 had elevated Lp(a), with incidence ~7% higher (~30% vs. ~23%) in Black, Pacific, and Native American groups. Of those with elevated Lp(a) levels, 96 (10.9%) had diagnoses (dxs) of VTE vs. 270 of 3129 (8.6%) participants with normal Lp(a) (p=0.046). Specifically, 9.76% of elevated Lp(a) participants vs. 7.51% of normal Lp(a) participants had dxs of DVT (p=0.035). No significant difference was found between elevated Lp(a) and PE. Additionally, 227 (25.8%) participants with elevated Lp(a) had VHD dxs compared to 593 (18.9%) participants from the normal Lp(a) cohort (p=0.0001). Specifically, 14.98% of elevated Lp(a) participants vs. 10.48% of normal Lp(a) participants had Aortic VHD (p=0.0003), and 14.87% of elevated Lp(a) participants vs. 10.35% normal Lp(a) participants had Mitral VHD (p=0.0003). No significant association was found between elevated Lp(a) and pulmonic or tricuspid VHD. Less novel but significant associations between elevated Lp(a) and Stroke (p=0.046) and CAD (p=0.0001) were also observed. Conclusions: In our study, elevated Lp(a) levels were significantly associated with increased risk of VTE and nonrheumatic VHD. An examination of these risks in association with germline genetic studies of ASCVD in the HNP is ongoing.
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