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Low nonfasting triglycerides and reduced all-cause mortality: a mendelian randomization study.
- Source :
-
Clinical chemistry [Clin Chem] 2014 May; Vol. 60 (5), pp. 737-46. Date of Electronic Publication: 2014 Jan 16. - Publication Year :
- 2014
-
Abstract
- Background: Increased nonfasting plasma triglycerides marking increased amounts of cholesterol in remnant lipoproteins are important risk factors for cardiovascular disease, but whether lifelong reduced concentrations of triglycerides on a genetic basis ultimately lead to reduced all-cause mortality is unknown. We tested this hypothesis.<br />Methods: Using individuals from the Copenhagen City Heart Study in a mendelian randomization design, we first tested whether low concentrations of nonfasting triglycerides were associated with reduced all-cause mortality in observational analyses (n = 13 957); second, whether genetic variants in the triglyceride-degrading enzyme lipoprotein lipase, resulting in reduced nonfasting triglycerides and remnant cholesterol, were associated with reduced all-cause mortality (n = 10 208).<br />Results: During a median 24 and 17 years of 100% complete follow-up, 9991 and 4005 individuals died in observational and genetic analyses, respectively. In observational analyses compared to individuals with nonfasting plasma triglycerides of 266-442 mg/dL (3.00-4.99 mmol/L), multivariably adjusted hazard ratios for all-cause mortality were 0.89 (95% CI 0.78-1.02) for 177-265 mg/dL (2.00-2.99 mmol/L), 0.74 (0.65-0.84) for 89-176 mg/dL (1.00-1.99 mmol/L), and 0.59 (0.51-0.68) for individuals with nonfasting triglycerides <89 mg/dL (<1.00 mmol/L). The odds ratio for a genetically derived 89-mg/dL (1-mmol/L) lower concentration in nonfasting triglycerides was 0.50 (0.30-0.82), with a corresponding observational hazard ratio of 0.87 (0.85-0.89). Also, the odds ratio for a genetically derived 50% lower concentration in nonfasting triglycerides was 0.43 (0.23-0.80), with a corresponding observational hazard ratio of 0.73 (0.70-0.77).<br />Conclusions: Genetically reduced concentrations of nonfasting plasma triglycerides are associated with reduced all-cause mortality, likely through reduced amounts of cholesterol in remnant lipoproteins.
- Subjects :
- Biomarkers blood
Cardiovascular Diseases blood
Cardiovascular Diseases genetics
Data Interpretation, Statistical
Denmark
Humans
Kaplan-Meier Estimate
Lipoprotein Lipase metabolism
Mortality trends
Postprandial Period
Prospective Studies
Sensitivity and Specificity
Triglycerides genetics
Cardiovascular Diseases mortality
Cholesterol blood
Lipoprotein Lipase genetics
Mendelian Randomization Analysis
Polymorphism, Genetic
Triglycerides blood
Subjects
Details
- Language :
- English
- ISSN :
- 1530-8561
- Volume :
- 60
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Clinical chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 24436475
- Full Text :
- https://doi.org/10.1373/clinchem.2013.219881