Influence of Lp(a) and systemic inflammation on all-cause mortality in a primary prevention population: data from our clinic database

Abstract

Abstract Background Epidemiological, pathophysiological, and genetic studies have established Lp(a) as a causal risk factor for development of cardiovascular (CVD) and valvular heart disease. However, there is controversy about how inflammation can modulate Lp(a) risk and major adverse cardiovascular events. We aim to investigate the influence of elevated Lp(a) and systemic inflammation on all-cause mortality in a primary prevention setting. Method We analyzed data obtained from the Preventive Cardiology Information System (PreCis), a database of clinical and laboratory information on 8,136 primary prevention patients seen at our clinic preventive cardiology clinic between 1st Jan 1999-12th Dec 2018. Primary prevention was defined as having no history of coronary artery disease (CAD), coronary and peripheral arterial revascularization, nor atherosclerosis. Lp(a) ≥50 mg/dL was considered as clinically elevated. The association between Lp(a) and the demographic and clinical variables of interest was examined using the student’s t-test or Chi-squared test. All-cause mortality was assessed using Kaplan-Meier estimates, and adjusted Cox proportional hazards models. All statistical analyses were conducted using SAS version 9.4. Result In the overall primary prevention population (n=8,136), the median age was 54 years, with 56.9% women and 84.8% being Caucasian. In this cohort, 21% had hypertension, and 5.5% had diabetes. The median Lp(a) was 21 mg/dL (interquartile interval 7-57 mg/dL). Lp(a) was ≥50 mg/dL in 29% of the population. Of those with elevated Lp(a) (n=2,368), 1,751 (73.9%) patients had hsCRP drawn. In this group, 782 patients (44.7%) had hsCRP <2 mg/L and 969 (55.3%) had hsCRP ≥2 mg/L. The all-cause mortality rate in individuals with elevated Lp(a) and hsCRP ≥2mg/L was 9.2% compared to 4.2% in those with elevated Lp(a) and hsCRP <2mg/L. In a multivariable Cox proportional hazard regression model adjusted for age and gender, in patients with elevated Lp(a), hsCRP ≥2 mg/L was significantly associated with all-cause mortality (HR 2.35, 95% CI (1.57-3.53), p>0.001) (Figure 1). Conclusion In a primary prevention population without established atherosclerosis, elevated Lp(a), increased systemic inflammation was associated with increased all-cause mortality. This finding supports the need for risk classification and targeted primary prevention management of higher risk patients with elevated Lp(a).