Beyond Cholesterol Lowering: Clinical Caution, Personalization, and Nutritional Integration in Statin Therapy

Background: Elevated low-density lipoprotein cholesterol (LDL-C) is a major risk factor
for atherosclerosis and cardiovascular disease (CVD). Statins are the cornerstone of LDL-C
reduction and are highly effective in secondary prevention. However, their benefit in
primary prevention among individuals at low-to-moderate cardiovascular risk remains
controversial, and long-term adherence is often limited by adverse effects. Methods: This
narrative review summarizes current evidence on the clinical effectiveness of statin ther
apy, with particular attention paid to the role of nutritional status in modulating statin
efficacy, safety, and interpretation of clinical outcomes. Results: In primary prevention the
effectiveness of statins in reducing cardiovascular events remains mixed. Furthermore,
20–30% of patients in secondary or high-risk prevention do not achieve clinically mean
ingful benefits despite adequate LDL-C lowering. More than half of statin-treated patients
discontinue therapy within two years, most commonly because of adverse effects, without
a corresponding increase in cardiovascular mortality. Emerging evidence suggests that
malnutrition and sarcopenia may significantly influence statin pharmacokinetics and phar
macodynamics, thereby affecting both therapeutic response and susceptibility to adverse
events. In addition, statin-induced lipid lowering may alter nutrition-related biomarkers,
potentially leading to misclassification or overestimation of malnutrition. Conclusions:
Although statins remain effective agents for lowering LDL-C, their prescription should
be embedded within an individualized, patient-centered approach. Current guidelines
provide a robust methodological framework for statin use; however, their application
should be contextualized rather than automatic. Optimal effectiveness is achieved when
pharmacological therapy is integrated with dietary patterns, nutritional status, and lifestyle
factors. Incorporating nutritional assessment into statin management may improve tolerability, enhance clinical outcomes, and enable more accurate cardiovascular risk stratification beyond standardized cholesterol-lowering strategies.