Editorial [ Reducing Cardiovascular Risk: Is Low-Density Lipoprotein-Cholesterol (LDL-C) Lowering Enough? ]

Low-density lipoprotein-cholesterol (LDL-C) lowering remains the main target of hypolipidemic therapy [1]. Statins are the most widely used evidence-based drugs for the management of dyslipidemia and to reduce the risk of cardiovascular (CV) events [2]. The main lipid “target” of statins is LDL-C levels but they also exert variable effects on highdensity lipoprotein-cholesterol (HDL-C) and triglycerides (TG) levels [3]. The recently published Long-term Event Monitoring (LEM) study included 21,139 Japanese patients with hypercholesterolemia (LDL-C = 171, HDL-C = 60 and TG = 166 mg/dl; 4.4, 1.6 and 1.9 mmol/l at baseline). All patients received fluvastatin (mean dose 22.7 ± 6.7 mg/day at study end). Overall, 1.7% (146/8563) and 1.1% (93/8563) of patients aged ≥ 65 years old experienced cardiac and cerebral events, compared with 1.1% (112/10,517) and 0.3% (28/10,517) of patients aged < 65 years old (p = 0.0002 and < 0.0001, respectively). The follow-up period for primary (n = 17,189) and secondary (n = 1,895) prevention was 5 and 3 years, respectively [4]. A post hoc analysis of the LEM study published in this issue of Current Vascular Pharmacology demonstrated that diabetes (DM), hypertension, TG and HDL-C had an impact on cardiac and cerebral events [5]. DM was strongly associated with CV events in both the primary and secondary prevention groups [5]. For primary prevention DM increased the incidence of cardiac events by 2.37-fold and cerebral events by 2.15-fold in patients without complications. For secondary prevention the corresponding increases in risk were 1.59- and 3.79-fold, respectively, in patients with cardiac complications. A surprising finding was that hypertension exerted a significant predictive value for events only in the primary but not in the secondary prevention group [5]. The better control of blood pressure in higher risk patients, mainly in the secondary prevention group, could account, at least in part, for this finding [5]. The role of several lipid profile components on primary or secondary prevention was another surprising finding of the LEM study. Particularly, high TG and low HDL-C levels and not high LDL-C levels were predictors of CV events in the secondary prevention group [5]. Also, in patients without complications, the atherogenic lipid profile (low HDL-C and high TG), but not LDL-C levels, was associated with increased cerebral events [5]. However, it is important to recognize that all patients were on treatment.