Risk Factors for Polyvascular Involvement in Patients With Peripheral Artery Disease: A Mendelian Randomization Study

Background Atherosclerosis in >1 vascular bed (ie, polyvascular disease), often a feature of peripheral artery disease (PAD), is associated with high morbidity and mortality. We sought to identify risk factors for polyvascular involvement in patients with PAD. Methods and Results We performed 2-s...

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Veröffentlicht in:Journal of the American Heart Association Jg. 9; H. 24; S. e017740
Hauptverfasser: Dikilitas, Ozan, Satterfield, Benjamin A., Kullo, Iftikhar J.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England John Wiley and Sons Inc 15.12.2020
Wiley
Schlagworte:
Aged
Algorithms
Aortic Aneurysm, Abdominal - epidemiology
Aortic Aneurysm, Abdominal - genetics
atherosclerosis
Atherosclerosis - mortality
blood pressure
Brief Communication
Cerebrovascular Disorders - epidemiology
Cerebrovascular Disorders - genetics
Coronary Disease - epidemiology
Coronary Disease - genetics
Female
Genetic Predisposition to Disease
Genome-Wide Association Study - methods
Glycated Hemoglobin - analysis
Humans
Hypertension - complications
Hypertension - genetics
lipoproteins
Lipoproteins - adverse effects
Lipoproteins - blood
Male
Mendelian randomization
Mendelian Randomization Analysis - methods
Middle Aged
Odds Ratio
Peripheral Arterial Disease - genetics
Peripheral Arterial Disease - pathology
peripheral artery disease
Phenotype
polyvascular disease
Risk Factors
Smoking - epidemiology
atherosclerosis
blood pressure
peripheral artery disease
Mendelian randomization
polyvascular disease
lipoproteins
ISSN:2047-9980, 2047-9980
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Zusammenfassung:Background Atherosclerosis in >1 vascular bed (ie, polyvascular disease), often a feature of peripheral artery disease (PAD), is associated with high morbidity and mortality. We sought to identify risk factors for polyvascular involvement in patients with PAD. Methods and Results We performed 2-sample Mendelian randomization using an inverse-variance-weighted approach, to assess 60 exposures including size and lipid content of atherogenic lipoproteins, blood pressure, glycated hemoglobin, and smoking as causal mediators for polyvascular disease in patients with PAD. Genetic instruments for these exposures were obtained from prior genome-wide association studies. Patients with PAD were from the Mayo Vascular Disease Biorepository, and polyvascular disease (ie, concomitant coronary heart disease, cerebrovascular disease, and/or abdominal aortic aneurysm) was ascertained by validated phenotyping algorithms. Of 3279 patients with PAD, 61% had polyvascular disease. Genetically predicted levels of the lipid content and/or particle measures of very small and small size very low-density lipoprotein, intermediate-density lipoprotein, and large low-density lipoprotein were associated with polyvascular disease: odds ratios (OR) of 1.80 (95% CI, 1.23-2.61), 1.70 (95% CI, 1.17-2.61), and 1.40 (95% CI, 1.09-1.80) per 1 SD increase in genetically determined levels, respectively. Both genetically predicted diastolic and systolic blood pressure were associated with polyvascular disease; OR per 10 mm Hg genetic increase in diastolic and systolic blood pressure were 1.66 (95% CI, 1.19-2.33) and 1.31 (95% CI, 1.07-1.60), respectively. Conclusions Lifetime exposure to increased lipid content and levels of very small and small very low-density lipoprotein, intermediate-density lipoprotein, and large low-density lipoprotein particles as well as elevated blood pressure are associated with polyvascular involvement in patients with PAD. Reduction in levels of such exposures may limit progression of atherosclerosis in patients with PAD.
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For Sources of Funding and Disclosures, see page 9.
Supplementary Material for this article is available at https://www.ahajournals.org/doi/suppl/10.1161/JAHA.120.017740
ISSN:2047-9980
2047-9980
DOI:10.1161/JAHA.120.017740