Triglycerides on the rise: should we swap seats on the seesaw?

Abstract

For decades, cardiovascular risk attributed to lipids beyond low-density lipoprotein (LDL) has focused appropriately on high-density lipoprotein (HDL). Indubitable observational data show a consistent inverse relationship between baseline HDL-C concentrations and cardiovascular risk. Yet, fidelity as a prospective risk marker does not guaranty that an analyte either lies in a causal pathway for disease, or that its therapeutic manipulation will yield clinical benefits. Indeed, multiple strategies to raise HDL levels therapeutically have thus far failed to forestall events in clinical trials [e.g. currently available fibrates, niacin, and the investigated cholesteryl ester transfer protein (CETP) inhibitors]. We await eagerly with an open mind, however, results from the ongoing outcome trials with two additional CETP inhibitors. We also recognize that steady-state concentrations of HDL-C in plasma likely do not reflect the flux of HDL particles, their potential for mediating reverse cholesterol transport, and other putative functions of HDL subclasses. For example, a large body of in vitro and experimental animal studies indicates that HDL particles may have many beneficial actions beyond reverse cholesterol transport. These putative properties of HDL particles include anti-oxidant and anti-inflammatory effects, attributes not assessed by the simple laboratory measurement of HDL-C. These functional facets of HDL may provide novel targets for therapeutic manipulation in a more subtle fashion in the future. Yet, concordant with the data from clinical intervention trials showing lack of benefit (or even harm) with current approaches to pharmacological boosting of HDL-C, recent genetic studies have also cast doubt on HDL-C as a causal risk factor.1 While HDL-C has stood in the spotlight, centre stage, triglycerides have tarried in the wings as a causal cardiovascular risk factor. Adjustment for …