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Remnant cholesterol, low-density lipoprotein cholesterol, and blood pressure as mediators from obesity to ischemic heart disease.
- Source :
-
Circulation research [Circ Res] 2015 Feb 13; Vol. 116 (4), pp. 665-73. Date of Electronic Publication: 2014 Nov 19. - Publication Year :
- 2015
-
Abstract
- Rationale: Obesity leads to increased ischemic heart disease (IHD) risk, but the risk is thought to be mediated through intermediate variables and may not be caused by increased weight per se.<br />Objective: To test the hypothesis that the increased IHD risk because of obesity is mediated through lipoproteins, blood pressure, glucose, and C-reactive protein.<br />Methods and Results: Approximately 90 000 participants from Copenhagen were included in a Mendelian randomization design with mediation analyses. Associations were examined using conventional measurements of body mass index and intermediate variables and using genetic variants associated with these. During ≤22 years of follow-up 13 945 participants developed IHD. The increased IHD risk caused by obesity was partly mediated through elevated levels of nonfasting remnant cholesterol and low-density lipoprotein cholesterol, through elevated blood pressure, and possibly also through elevated nonfasting glucose levels; however, reduced high-density lipoprotein cholesterol and elevated C-reactive protein levels were not mediators in genetic analyses. The 3 intermediate variables that explained the highest excess risk of IHD from genetically determined obesity were low-density lipoprotein cholesterol with 8%, systolic blood pressure with 7%, and remnant cholesterol with 7% excess risk of IHD. Corresponding observational excess risks using conventional body mass index were 21%, 11%, and 20%, respectively.<br />Conclusions: The increased IHD risk because of obesity was partly mediated through elevated levels of nonfasting remnant and low-density lipoprotein cholesterol and through elevated blood pressure. Our results suggest that there may be benefit to gain by reducing levels of these risk factors in obese individuals not able to achieve sustained weight loss.<br /> (© 2014 American Heart Association, Inc.)
- Subjects :
- Adult
Aged
Biomarkers blood
Body Mass Index
Denmark
Female
Gene Frequency
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Male
Middle Aged
Myocardial Ischemia blood
Myocardial Ischemia diagnosis
Myocardial Ischemia genetics
Myocardial Ischemia physiopathology
Obesity blood
Obesity diagnosis
Obesity genetics
Obesity physiopathology
Phenotype
Prognosis
Prospective Studies
Risk Assessment
Risk Factors
Time Factors
Blood Pressure
Cholesterol blood
Cholesterol, LDL blood
Myocardial Ischemia etiology
Obesity complications
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4571
- Volume :
- 116
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Circulation research
- Publication Type :
- Academic Journal
- Accession number :
- 25411050
- Full Text :
- https://doi.org/10.1161/CIRCRESAHA.116.304846