Low Nonfasting Triglycerides and Reduced All-Cause Mortality: A Mendelian Randomization Study

TY - JOUR

T1 - Low Nonfasting Triglycerides and Reduced All-Cause Mortality

T2 - A Mendelian Randomization Study

AU - Thomsen, Mette

AU - Varbo, Anette

AU - Tybjærg-Hansen, Anne

AU - Nordestgaard, Børge G

PY - 2014/5

Y1 - 2014/5

N2 - 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. 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 triglyceridedegrading enzyme lipoprotein lipase, resulting in reduced nonfasting triglycerides and remnant cholesterol, were associated with reduced all-cause mortality (n = 10 208). 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). CONCLUSIONS: Genetically reduced concentrations of nonfasting plasma triglycerides are associated with reduced all-cause mortality, likely through reduced amounts of cholesterol in remnant lipoproteins.

AB - 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. 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 triglyceridedegrading enzyme lipoprotein lipase, resulting in reduced nonfasting triglycerides and remnant cholesterol, were associated with reduced all-cause mortality (n = 10 208). 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). CONCLUSIONS: Genetically reduced concentrations of nonfasting plasma triglycerides are associated with reduced all-cause mortality, likely through reduced amounts of cholesterol in remnant lipoproteins.

KW - Biological Markers

KW - Cardiovascular Diseases

KW - Cholesterol

KW - Data Interpretation, Statistical

KW - Denmark

KW - Humans

KW - Kaplan-Meier Estimate

KW - Lipoprotein Lipase

KW - Mendelian Randomization Analysis

KW - Mortality

KW - Polymorphism, Genetic

KW - Postprandial Period

KW - Prospective Studies

KW - Sensitivity and Specificity

KW - Triglycerides

U2 - 10.1373/clinchem.2013.219881

DO - 10.1373/clinchem.2013.219881

M3 - Journal article

C2 - 24436475

SN - 0009-9147

VL - 60

SP - 737

EP - 746

JO - Clinical Chemistry

JF - Clinical Chemistry

IS - 5

ER -