PLTP activity is a risk factor for subsequent cardiovascular events in CAD patients under statin therapy: the AtheroGene Study

Abstract

Phospholipid transferprotein (PLTP) mediates both net transfer and exchange of phospholipids between different lipoproteins. Although many studies have investigated the role of PLTP in atherogenesis, the role of PLTP in atherosclerotic diseases is unclear. We investigated the association of serum PLTP activity with the incidence of a combined endpoint (myocardial infarction and cardiovascular death) and its relation to other markers of atherosclerosis in 1,085 patients with angiographically documented coronary artery disease (CAD). In the median follow-up of 5.1 years, 156 patients had suffered from the combined endpoint of myocardial infarction or cardiovascular death including 47 of 395 patients who were on statins at baseline. In KaplanMeyer analyses serum PLTP activity was not associated with the combined endpoint in all patients. However, in the subgroup of patients receiving statins at baseline, PLTP was shown to be a significant predictor of cardiovascular outcome (P 5 0.019), and this also remained stable in univariate (P 5 0.027) and multivariate cox regression analyses (P 5 0.041) including potential confounders (classical risk factors, HDL cholesterol (HDL-C), and others). We showed in our study that, under statin treatment, high plasma PLTP activity was related to fatal and nonfatal cardiovascular events in CAD patients.-Schlitt, A

PLTP activity inversely correlates with CAAD: effects of PON1 enzyme activity and genetic variants on PLTP activity

“…This fi nding of poor correlation in male controls not on statin pharmacotherapy is in contrast with prior reports of high concordance ( r = 0.90) between the two methods (36)(37)(38). Similar to the high correlation between HDL-C and HDL-P in MESA ( r = 0.69) but the lack of HDL-C to predict cIMT in a multivariate model including HDL-P ( 7 ), the relative lack of correlation observed between the two PLTPa assays (see Fig.…”

“…Additionally, one prospective study of 1,085 participants with angiographically documented CHD at baseline has reported a positive association between PLTPa and the composite outcome of incident MI and death ( 38 ). A separate prospective study of 2,679 participants without known CVD at baseline from the Framingham Heart Study found that PLTP higher than the median was a risk factor for incident CVD in males only ( 36 ).…”

“…PLTPa was measured in a subset of 20 male CLEAR participants without CAAD and not taking statin pharmacotherapy using two methods: 1 ) the previously described radiometric assay; and 2 ) using a commercial fl uorometric assay from Roar Biomedical, Inc, previously used in numerous studies of PLTPa and CVD (36)(37)(38). In brief, 3 l of sample plasma was incubated with kit-provided donor and acceptor particles resulting in the PLTP-mediated transfer of fl uorescent phospholipid.…”

“…Several studies have associated PLTPa with increased risk of coronary heart disease (CHD) ( 31, [36][37][38]. However, cardioprotective effects of PLTPa have also been reported for peripheral artery disease ( 39 ).…”

Genetic and nongenetic sources of variation in phospholipid transfer protein activity

“…While studies have associated elevated PLTP with coronary artery disease ( 18 ), left ventricular dysfunction ( 19 ), and coronary artery events in subjects on statins ( 20 ), the opposite result was reported for peripheral artery disease. Peripheral artery vascular disease has been associated with lower PLTP ( 21 ), while carotida intima-media thickness ( 22 ) has been associated with raised PLTP in humans.…”