Lipoprotein Particle Profiles, Standard Lipids, and Peripheral Artery Disease Incidence
- PMID: 30021845
- PMCID: PMC6343136
- DOI: 10.1161/CIRCULATIONAHA.118.035432
Lipoprotein Particle Profiles, Standard Lipids, and Peripheral Artery Disease Incidence
Abstract
Background: Despite strong and consistent prospective associations of elevated low-density lipoprotein (LDL) cholesterol concentration with incident coronary and cerebrovascular disease, data for incident peripheral artery disease (PAD) are less robust. Atherogenic dyslipidemia characterized by increased small LDL particle (LDL-P) concentration, rather than total LDL cholesterol content, along with elevated triglyceride-rich lipoproteins and low high-density lipoprotein (HDL) cholesterol (HDL-C), may be the primary lipid driver of PAD risk.
Methods: The study population was a prospective cohort study of 27 888 women ≥45 years old free of cardiovascular disease at baseline and followed for a median of 15.1 years. We tested whether standard lipid concentrations, as well as nuclear magnetic resonance spectroscopy-derived lipoprotein measures, were associated with incident symptomatic PAD (n=110) defined as claudication and/or revascularization.
Results: In age-adjusted analyses, while LDL cholesterol was not associated with incident PAD, we found significant associations for increased total and small LDL-P concentrations, triglycerides, and concentrations of very LDL (VLDL) particle (VLDL-P) subclasses, increased total cholesterol (TC):HDL-C, low HDL-C, and low HDL particle (HDL-P) concentration (all P for extreme tertile comparisons <0.05). Findings persisted in multivariable-adjusted models comparing extreme tertiles for elevated total LDL-P (adjusted hazard ratio [HRadj] 2.03; 95% CI, 1.14-3.59), small LDL-P (HRadj 2.17; 95% CI, 1.10-4.27), very large VLDL-P (HRadj 1.68; 95% CI, 1.06-2.66), medium VLDL-P (HRadj 1.98; 95% CI, 1.15-3.41), and TC:HDL-C (HRadj, 3.11; 95% CI, 1.67-5.81). HDL was inversely associated with risk; HRadj for extreme tertiles of HDL-C and HDL-P concentration were 0.30 ( P trend < 0.0001) and 0.29 ( P trend < 0.0001), respectively. These components of atherogenic dyslipidemia, including small LDL-P, medium and very large VLDL-P, TC:HDL-C, HDL-C, and HDL-P, were more strongly associated with incident PAD than incident coronary and cerebrovascular disease. Finally, the addition of LDL-P and HDL-P concentration to TC:HDL-C measures identified women at heightened PAD risk.
Conclusions: In this prospective study, nuclear magnetic resonance-derived measures of LDL-P, but not LDL cholesterol, were associated with incident PAD. Other features of atherogenic dyslipidemia, including elevations in TC:HDL-C, elevations in triglyceride-rich lipoproteins, and low standard and nuclear magnetic resonance-derived measures of HDL, were significant risk determinants. These data help clarify prior inconsistencies and may elucidate a unique lipoprotein signature for PAD compared to coronary and cerebrovascular disease.
Clinical trial registration: URL: https://www.clinicaltrials.gov/ . Unique Identifier: NCT00000479.
Keywords: coronary artery disease; lipoproteins; magnetic resonance spectroscopy; peripheral artery disease.
Figures
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Comment in
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Response by Vedel et al to Letters Regarding Article, "High-Target Versus Low-Target Blood Pressure Management During Cardiopulmonary Bypass to Prevent Cerebral Injury in Cardiac Surgery Patients: A Randomized Controlled Trial".Circulation. 2018 Nov 20;138(21):2447-2448. doi: 10.1161/CIRCULATIONAHA.118.036490. Circulation. 2018. PMID: 30571581 No abstract available.
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Unraveling the Risk of Peripheral Artery Disease.Circulation. 2018 Nov 20;138(21):2342-2344. doi: 10.1161/CIRCULATIONAHA.118.036347. Circulation. 2018. PMID: 30571589 No abstract available.
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References
-
- Ridker PM, Stampfer MJ, Rifai N. Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease. JAMA 2001;285:2481–2485. doi:10.1001/jama.285.19.2481. - DOI - PubMed
-
- Kennedy M, Solomon C, Manolio TA, Criqui MH, Newman AB, Polak JF, Burke GL, Enright P, Cushman M. Risk factors for declining ankle-brachial index in men and women 65 years or older: the Cardiovascular Health Study. Arch Intern Med 2005;165:1896–1902. doi: 10.1001/archinte.165.16.1896. - DOI - PubMed
-
- Pérez de Isla L, Alonso R, Mata N, Saltijeral A, Muñiz O, Rubio-Marin P, Diaz-Diaz JL, Fuentes F, de Andrés R, Zambón D, Galiana J, Piedecausa M, Aguado R, Mosquera D, Vidal JI, Ruiz E, Manjón L, Mauri M, Padró T, Miramontes JP, Mata P, SAFEHEART Investigators. Coronary Heart Disease, Peripheral Arterial Disease, and Stroke in Familial Hypercholesterolaemia: Insights From the SAFEHEART Registry (Spanish Familial Hypercholesterolaemia Cohort Study). Arterioscler Thromb Vasc Biol 2016;36:2004–2010. doi: 10.1161/ATVBAHA.116.307514. - DOI - PubMed
-
- Allison MA, Criqui MH, McClelland RL, Scott JM, McDermott MM, Liu K, Folsom AR, Bertoni AG, Sharrett AR, Homma S, Kori S. The Effect of Novel Cardiovascular Risk Factors on the Ethnic-Specific Odds for Peripheral Arterial Disease in the Multi-Ethnic Study of Atherosclerosis (MESA). J Am Coll Cardiol 2006;48:1190–1197. doi: 10.1016/j.jacc.2006.05.049. - DOI - PubMed
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