scholarly journals Prioritizing the Role of Major Lipoproteins and Subfractions as Risk Factors for Peripheral Artery Disease

Circulation ◽  
2021 ◽  
Author(s):  
Michael G. Levin ◽  
Verena Zuber ◽  
Venexia M. Walker ◽  
Derek Klarin ◽  
Julie Lynch ◽  
...  
Keyword(s):  
Risk Factors ◽  
Peripheral Artery Disease ◽  
Drug Targets ◽  
Particle Concentration ◽  
Peripheral Artery ◽  
Lipoprotein Subfractions ◽  
Artery Disease ◽  
Lowering Drug ◽  
Cad Risk

Background: Lipoprotein-related traits have been consistently identified as risk factors for atherosclerotic cardiovascular disease, largely on the basis of studies of coronary artery disease (CAD). The relative contributions of specific lipoproteins to risk of peripheral artery disease (PAD) have not been well-defined. We leveraged large-scale genetic association data to investigate effects of circulating lipoprotein-related traits on PAD risk. Methods: Genome-wide association study summary statistics for circulating lipoprotein-related traits were used in the MR Bayesian model averaging framework to prioritize the most likely causal major lipoprotein and subfraction risk factors for PAD and CAD. MR was used to estimate the effect of ApoB-lowering on PAD risk using gene regions proxying lipid-lowering drug targets. Genes relevant to prioritized lipoprotein subfractions were identified using transcriptome-wide association studies. Results: ApoB was identified as the most likely causal lipoprotein-related risk factor for both PAD (marginal inclusion probability [MIP] 0.86, p = 0.003) and CAD (MIP 0.92, p = 0.005). Genetic proxies for ApoB (apolipoprotein B)-lowering medications were associated with reduced risk of both PAD (OR 0.87 per 1 standard deviation decrease in ApoB, 95% CI 0.84 to 0.91, p = 9 x 10 -10 ) and CAD (OR 0.66, 95% CI 0.63 to 0.69, p = 4 x 10 -73 ), with a stronger predicted effect of ApoB-lowering on CAD (ratio of effects 3.09, 95% CI 2.29 to 4.60, p < 1 × 10 -6 ). Extra-small-VLDL particle concentration (XS.VLDL.P) was identified as the most likely subfraction associated with PAD risk (MIP 0.91, p = 2.3 x 10 -4 ), while large-LDL particle concentration (L.LDL.P) was the most likely subfraction associated with CAD risk (MIP 0.95, p = 0.011). Genes associated with XS.VLDL.P and L.LDL.P included canonical ApoB-pathway components, although gene-specific effects were variable. Lipoprotein(a) was associated with increased risk of PAD, independent of ApoB (OR 1.04, 95% CI 1.03 to 1.04, 95% CI 1.0 x 10 -33 ). Conclusions: ApoB was prioritized as the major lipoprotein fraction causally responsible for both PAD and CAD risk. However, ApoB-lowering drug targets and ApoB-containing lipoprotein subfractions had diverse associations with ASCVD, and distinct subfraction-associated genes suggest possible differences in the role of lipoproteins in the pathogenesis of PAD and CAD.

scholarly journals Prioritizing the Role of Major Lipoproteins and Subfractions as Risk Factors for Peripheral Artery Disease

2021 ◽  
Author(s):  
Michael G. Levin ◽  
Verena Zuber ◽  
Venexia M. Walker ◽  
Derek Klarin ◽  
Julie Lynch ◽  
...  
Keyword(s):  
Risk Factors ◽  
Drug Targets ◽  
Particle Concentration ◽  
Mendelian Randomization ◽  
Inclusion Probability ◽  
Lipoprotein Subfractions ◽  
Artery Disease ◽  
Lowering Drug ◽  
Cad Risk

ABSTRACTBackgroundCirculating lipid and lipoprotein levels have consistently been identified as risk factors for atherosclerotic cardiovascular disease (ASCVD), largely on the basis of studies focused on coronary artery disease (CAD). The relative contributions of specific lipoproteins to risk of peripheral artery disease (PAD) have not been well-defined. Here, we leveraged large scale genetic association data to identify genetic proxies for circulating lipoprotein-related traits, and employed Mendelian randomization analyses to investigate their effects on PAD risk.MethodsGenome-wide association study summary statistics for PAD (Veterans Affairs Million Veteran Program, 31,307 cases) and CAD (CARDIoGRAMplusC4D, 60,801 cases) were used in the Mendelian Randomization Bayesian model averaging (MR-BMA) framework to prioritize the most likely causal major lipoprotein and subfraction risk factors for PAD and CAD. Mendelian randomization was used to estimate the effect of apolipoprotein B lowering on PAD risk using gene regions that proxy potential lipid-lowering drug targets. Transcriptome-wide association studies were performed to identify genes relevant to circulating levels of prioritized lipoprotein subfractions.ResultsApoB was identified as the most likely causal lipoprotein-related risk factor for both PAD (marginal inclusion probability 0.86, p = 0.003) and CAD (marginal inclusion probability 0.92, p = 0.005). Genetic proxies for ApoB-lowering medications were associated with reduced risk of both PAD (OR 0.87 per 1 standard deviation decrease in ApoB, 95% CI 0.84 to 0.91, p = 9 × 10−10) and CAD (OR 0.66, 95% CI 0.63 to 0.69, p = 4 × 10−73), with a stronger predicted effect of ApoB-lowering on CAD (ratio of ORs 1.33, 95% CI 1.25 to 1.42, p = 9 × 10−19). Among ApoB-containing subfractions, extra-small VLDL particle concentration (XS.VLDL.P) was identified as the most likely subfraction associated with PAD risk (marginal inclusion probability 0.91, p = 2.3 × 10−4), while large LDL particle concentration (L.LDL.P) was the most likely subfraction associated with CAD risk (marginal inclusion probability 0.95, p = 0.011). Genes associated with XS.VLDL.P and L.LDL.P included canonical ApoB-pathway components, although gene-specific effects varied across the lipoprotein subfractions.ConclusionApoB was prioritized as the major lipoprotein fraction causally responsible for both PAD and CAD risk. However, diverse effects of ApoB-lowering drug targets and ApoB-containing lipoprotein subfractions on ASCVD, and distinct subfraction-associated genes suggest possible biologic differences in the role of lipoproteins in the pathogenesis of PAD and CAD.

The role of protein-bound uremic toxins on peripheral artery disease and vascular access failure in patients on hemodialysis

2012 ◽  
Vol 225 (1) ◽  
pp. 173-179 ◽  
Author(s):  
Cheng-Jui Lin ◽  
Chi-Feng Pan ◽  
Hsuan-Liang Liu ◽  
Chih-Kuang Chuang ◽  
Thanasekaran Jayakumar ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Vascular Access ◽  
Uremic Toxins ◽  
Peripheral Artery ◽  
Artery Disease

scholarly journals Prevalence and risk factors of peripheral artery disease in black Africans with HIV infection: a cross-sectional hospital-based study

2018 ◽  
Vol Volume 14 ◽  
pp. 401-408 ◽  
Author(s):  
Félicité Kamdem ◽  
Yacouba Mapoure ◽  
Ba Hamadou ◽  
Fanny Souksouna ◽  
Marie Solange Doualla ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hiv Infection ◽  
Peripheral Artery Disease ◽  
Peripheral Artery ◽  
Cross Sectional ◽  
Black Africans ◽  
Artery Disease

scholarly journals Role of microRNAs in peripheral artery disease (Review)

2012 ◽  
Vol 6 (4) ◽  
pp. 695-700 ◽  
Author(s):  
XIANGYU ZHOU ◽  
PING YUAN ◽  
YANZHENG HE
Keyword(s):  
Peripheral Artery Disease ◽  
Peripheral Artery ◽  
Artery Disease

Are primary care physicians aware of peripheral artery disease risk reduction and management in the Saudi healthcare transformation era? A health cluster observational study

Vascular ◽  
2021 ◽  
pp. 170853812110443
Author(s):  
Sultan Alsheikh ◽  
Hesham AlGhofili ◽  
Omar A Alayed ◽  
Abdulkareem Aldrak ◽  
Kaisor Iqbal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Primary Care ◽  
Saudi Arabia ◽  
Risk Reduction ◽  
Peripheral Artery Disease ◽  
Primary Care Physicians ◽  
Primary Care Providers ◽  
Care Providers ◽  
Peripheral Artery ◽  
Artery Disease

Introduction Patients with peripheral artery disease (PAD) are often underdiagnosed and undertreated. This study aimed to assess the knowledge of the recommended target levels of blood pressure, low-density lipoprotein cholesterol, glycosylated hemoglobin A1C, and knowledge and attitude about PAD risk reduction therapies among physicians working in primary care settings in Saudi Arabia. Methods This observational cross-sectional study included family medicine consultants, residents, and general practitioners working in a health cluster in the capital city of Saudi Arabia using a self-administered questionnaire. Results Of the 129 physicians who completed the survey, 55% had completed PAD-related continuing medical education hours within the past 2 years. Despite this, the knowledge score of the recommended target levels was high in only 13.2% of the participants. Antiplatelet therapy was prescribed by 68.2% of the participants. Conclusion Here we identified the knowledge and action gaps among primary care providers in Saudi Arabia. Physicians had an excellent attitude about screening for and counseling about risk factors. However, they showed less interference in reducing these risk factors. We recommend addressing these knowledge gaps early in medical school and residency programs.

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