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COMMENT

There is accumulating evidence to support a role for elevated TG (a surrogate for TG-rich lipoproteins and their cholesterol load) in the causal pathway for atherosclerosis (1,2). Persistent uncertainty remains, however, regarding the level at which elevated TG become clinically relevant. The current study aimed to provide insights into this question by investigating the association of TG and subclinical atherosclerosis and vascular inflammation as early markers of cardiovascular events in moderate to low-risk individuals. The PESA cohort used in this report was appropriate, given that the majority (85%) of individuals were at low cardiovascular risk.

The results of this study show that already at TG 100-149 mg/dL there is evidence of increased prevalence of subclinical atherosclerosis in this lower-risk cohort. For individuals with TG ≥150 mg/dL this association was significant, both for all atherosclerotic plaques and non-coronary plaques (35% increase in prevalence compared with individuals with TG<100 mg/dL, p<0.001). Furthermore, this association was present even in individuals with ‘normal’ LDL-C levels, according to guideline-recommended goals (3). Serum TG levels were also associated with general arterial inflammation and with inflamed atherosclerotic plaques, a precursor of cardiovascular risk. While these findings do not demonstrate causality, they lend support to the premise that therapeutic strategies aimed at lowering TG levels, even in individuals at moderate to low risk with normal LDL-C levels, can improve cardiovascular disease prevention.

The findings from this study also have relevance for considerations relating to the ‘goal’ for TG-lowering therapy. Currently, the 2019 European Society of Cardiology/European Atherosclerosis Society dyslipidemia guidelines advise that a TG level <150 mg/dL (<1.7 mmol/L) is desirable but fall short of recommending TG goals due to insufficient data from cardiovascular outcomes studies. In high to very high-risk patients with TG levels >200 mg/dL (2.3 mmoL/L), statin treatment is recommended if lifestyle intervention is inadequate (3).

Taken together, these findings from the PESA study have relevance for reconsideration of the level at which TG should be targeted for therapeutic intervention. In lower risk individuals with elevated TG this may help to delay progression of subclinical cardiovascular disease, even if LDL-C levels are normal. Furthermore, among individuals at higher risk, targeting TG ≥150 mg/dL may reduce the residual risk of cardiovascular events among a background of well-controlled LDL-C levels. Results from the PROMINENT trial with pemafibrate will provide critical insights (4).