Predictors of Residual Cardiovascular Risk in Patients on Statin Therapy for Primary Prevention

Abstract

Background: Low-density lipoprotein cholesterol-lowering therapy is an important aspect of primary prevention of cardiovascular disease (CVD). Statins are the most widely used drug therapy for achieving low-density lipoprotein goals based on an individual’s 10-year risk. However, substantial risk of CVD events still exists even when a person is on statins. We sought to explore the predictors of future CVD events in individuals on statins with no pre-existing CVD. Methods: The analysis was done on subjects who were on statins (n = 919) at baseline in the Multi-Ethnic Study of Atherosclerosis limited access dataset from the National Heart, Lung and Blood Institute. The primary outcome variable was all-cause CVD events (n = 67). Multivariate regression Cox proportional hazard analysis was done to identify potential independent predictors of all-cause CVD. Results: Our cohort consisted of 47% males, with a mean age of 66 ± 9 years. Sixty-seven participants (7.3%) experienced CVD events during a mean follow-up of 4.4 years. A higher coronary artery calcium score, homocysteine levels, waist circumference and a lower large arterial elasticity index were identified as independent predictors of CVD events. Conclusion: Homocysteine, waist circumference, coronary artery calcification and the large artery elasticity index appear to be the major independent predictors of CVD events in individuals on statins with no pre-existing CVD. In addition to emphasizing weight loss, alternative approaches beyond lipid reduction may need to be explored to better characterize and attenuate the residual risk in subjects on statin therapy for primary prevention.

High residual cardiovascular risk after lipid-lowering: prime time for Predictive, Preventive, Personalized, Participatory, and Psycho-cognitive medicine

“…Indeed, Dhaliwal et al showed in a cohort study with subjects with no previous diabetes, heart attack, or stroke that WC and waist-to-hip ratio (WHR) both independently predicted CV deaths, whereas BMI did not have any predictive value ( 181 ). CRP, marker of inflammation, did not differ between the group that experienced CVD and the group without CVD, suggesting that WC is independently associated with CVD regardless of inflammation ( 182 ). However, abdominal obesity was associated with inflammation since adipose tissue was considered to generate inflammatory cytokines leading to a higher inflammatory profile in obese individuals ( 183 ).…”

Molecular sources of residual cardiovascular risk, clinical signals, and innovative solutions: relationship with subclinical disease, undertreatment, and poor adherence: implications of new evidence upon optimizing cardiovascular patient outcomes

“…In patients being treated with statin drugs for primary prevention, a number of predictors for residual risk have been identified, including waist circumference, large artery elasticity index, homocysteine, and coronary artery calcification 404. In the large JUPITER trial, statin-treated patients with low LDL cholesterol but high C-reactive protein levels had residual risk that was unrelated to either HDL cholesterol or triglyceride concentrations 139,140.…”

Modified Low Density Lipoprotein and Lipoprotein-Containing Circulating Immune Complexes as Diagnostic and Prognostic Biomarkers of Atherosclerosis and Type 1 Diabetes Macrovascular Disease

“…The markers generally measured for diagnosing of atherosclerosis are lipid parameters of the blood, in particular cholesterol [ 5 ]. Even though the direct link between the reduction of cholesterol and the regression of atherosclerosis is not unarguably established [ 6 , 7 , 8 ], cholesterol is still the key target parameter in the existing anti-atherosclerotic therapy [ 9 ]. It is worth noting here that the obtained data about a relation of apolipoproteins to risk scores led to slight improvement in cardiovascular disease risk prediction [ 10 ].…”