Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Circulation. 2018 Apr 4. pii: CIRCULATIONAHA.117.032318. doi: 10.1161/CIRCULATIONAHA.117.032318. [Epub ahead of print]

Triglyceride-Rich Lipoprotein Cholesterol and Risk of Cardiovascular Events Among Patients Receiving Statin Therapy in the Treating to New Targets (TNT) Trial.

Author information

1
Imperial Centre for Cardiovascular Disease Prevention (ICCP), Department of Primary Care and Public Health, School of Public Health, Imperial College London; London, UK.
2
Pfizer, New York, NY.
3
Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands.
4
Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
5
School of Medical Sciences, University of New South Wales Australia, Sydney, NSW, Australia.
6
Division of Cardiology, Zuckerberg San Francisco General Hospital, San Francisco, CA.
7
Imperial Centre for Cardiovascular Disease Prevention (ICCP), Department of Primary Care and Public Health, School of Public Health, Imperial College London; London, UK k.ray@imperial.ac.uk.

Abstract

Background -Mendelian randomization data suggest genetic determinants of lifetime higher triglyceride-rich lipoprotein-cholesterol (TRL-C) are causally related to cardiovascular disease and therefore a potential therapeutic target. The relevance of TRL-C among patients receiving statins is unknown. We assessed the relationship between TRL-C and cardiovascular risk, and whether this risk was modifiable among patients receiving statins in the TNT trial. Methods -Patients with coronary heart disease [CHD] and LDL-C 130-250mg/dL entered an 8-week run-in phase with atorvastatin 10mg/day (ATV10). After this period, participants with LDL-C <130mg/dL entered the randomised phase with ATV10 (n=5006) vs. atorvastatin 80mg/day (ATV80, n=4995). Primary endpoint: CHD death, non-fatal myocardial infarction, resuscitated cardiac arrest, or stroke (major adverse cardiovascular events [MACE]). TRL-C was calculated as total cholesterol minus HDL-C minus LDL-C. The effect of atorvastatin on TRL-C was assessed during the run-in phase (ATV10) and randomised phase (ATV80 vs. ATV10). The risk of MACE was assessed across quintiles (Q) of baseline TRL-C (and, for comparison, by baseline triglycerides and non-HDL-C) during the randomised period. Finally, the association between TRL-C changes with atorvastatin and cardiovascular risk was assessed by multivariate Cox-regression. Results -ATV10 reduced TRL-C a 10.7% from an initial TRL-C of 33.9±16.6 mg/dL. ATV80 led to an additional 15.4% reduction. Cardiovascular risk factors positively correlated with TRL-C. Among patients receiving ATV10, higher TRL-C associated higher 5-year MACE rates (Q1=9.7%, Q5=13.8%; HR Q5-vs-Q1: 1.48 [95%CI 1.15-1.92]; p-trend<0.0001). ATV80 (vs. ATV10) did not significantly alter the risk of MACE in Q1-Q2, but significantly reduced risk in Q3-Q5 (RRR: 29%-41%; all p<0.0250), with evidence of effect modification (p-homogeneity=0.0053); results were consistent for triglycerides (p-homogeneity=0.0101) and directionally similar for non-HDL-C (p-homogeneity=0.1387). Finally, in adjusted analyses, a 1SD percentage reduction in TRL-C with atorvastatin resulted in a significant lower risk of MACE (HR 0.93, 95%CI 0.86-1.00, p=0.0482) independent of the reduction in LDL-C and of similar magnitude to that per 1SD lowering in LDL-C (HR 0.89, 95%CI 0.83-0.95, p=0.0008). Conclusions -The present post-hoc analysis from TNT shows that increased TRL-C levels associate an increased cardiovascular risk and provides evidence for the cardiovascular benefit of lipid-lowering with statins among CHD patients with high TRL-C. Clinical Trial Registration -URL: https://clinicaltrials.gov Unique Identifier: NCT00327691.

KEYWORDS:

Non-HDL cholesterol; Remnants; TNT trial; Triglyceride-rich lipoproteins; atorvastatin; cardiovascular risk; statin therapy; triglycerides

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center