Dataset Information

Lipoprotein-Associated Phospholipase A2 and Incident Peripheral Arterial Disease in Older Adults: The Cardiovascular Health Study.

ABSTRACT: Although prior studies report a relationship between elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) and incident cardiovascular disease, the prospective association of Lp-PLA2 with incident peripheral arterial disease (PAD) has not been studied. We investigated the association between Lp-PLA2 mass and activity and the risk of developing clinical PAD and low ankle-brachial index (ABI).Among Cardiovascular Health Study participants, a population-based cohort of 5888 adults aged ?65 years enrolled in 1989 to 1990, Lp-PLA2 mass and activity were measured in 4537 individuals without baseline PAD. Clinical PAD, defined as leg artery revascularization or diagnosed claudication, was ascertained through 2011. Incident low ABI, defined as ABI <0.9 and decline of ?0.15, was assessed among 3537 individuals who had an ABI >0.9 at baseline and a second ABI measurement 3 or 6 years later. Analyses were adjusted for demographics, cholesterol, smoking, comorbidities, and C-reactive protein. Each standard deviation increment in Lp-PLA2 mass (117 ng/mL) was associated with a higher risk of developing clinical PAD (hazard ratio 1.28; 95% confidence interval 1.13, 1.45) and incident low ABI (odds ratio 1.16; 95% confidence interval 1.00, 1.33). Results per standard deviation increment in Lp-PLA2 activity (13 nmol/min per mL) were similar for clinical PAD (hazard ratio 1.24; 95% confidence interval 1.07, 1.44) and low ABI (odds ratio 1.28; 95% confidence interval 1.09, 1.50).Higher Lp-PLA2 mass and activity were associated with development of both incident clinical PAD and low ABI. Future studies are needed to determine whether pharmacological inhibition of Lp-PLA2 reduces the incidence of PAD.

SUBMITTER: Garg PK

PROVIDER: S-EPMC4808367 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Lipoprotein-Associated Phospholipase A2 and Incident Peripheral Arterial Disease in Older Adults: The Cardiovascular Health Study.

Garg Parveen K PK Arnold Alice M AM Hinckley Stukovsky Karen D KD Koro Carol C Jenny Nancy S NS Mukamal Kenneth J KJ Criqui Michael H MH Furberg Curt D CD Newman Anne B AB Cushman Mary M

Arteriosclerosis, thrombosis, and vascular biology 20160204 4

<h4>Objective</h4>Although prior studies report a relationship between elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) and incident cardiovascular disease, the prospective association of Lp-PLA2 with incident peripheral arterial disease (PAD) has not been studied. We investigated the association between Lp-PLA2 mass and activity and the risk of developing clinical PAD and low ankle-brachial index (ABI).<h4>Approach and results</h4>Among Cardiovascular Health Study participants, a popu ...[more]

PMID: 26848158

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Project description:BackgroundLipoprotein-associated Phospholipase A2 (Lp-PLA2), can exert proinflammatory as well as proatherogenic properties on the vascular wall. The current study sought to evaluate the influence of high Lp-PLA2 levels on indices of arterial wall properties in patients with stable coronary artery disease (CAD).MethodsThree hundred seventy-four consecutive patients with stable CAD (mean age 61 ± 11 years, 89% males) were enrolled in this single-center cross-sectional study. Flow-mediated dilation (FMD) was used to assess endothelial function and augmentation index (AIx) of the central aortic pressure was used to assess reflected waves. ELISA was used to determine Lp-PLA2 serum levels.ResultsAfter dividing the participants in 3 equal groups based on the tertiles of circulating Lp-PLA2 values, no significant differences were demonstrated between those in the 3rd tertile with Lp-PLA2 values > 138 μg/L, in the 2nd tertile with Lp-PLA2 values between 101 and 138 μg/L and in the 1st tertile (Lp-PLA2 values < 101 μg/L) regarding age, male gender, smoking habits, family history of CAD or history of a previous myocardial infarction, diabetes mellitus, arterial hypertension, hyperlipidemia, duration of CAD and treatment with relevant medication. Importantly, subjects with Lp-PLA2 values in the highest tertile, had significantly reduced FMD values compared to the middle and lower tertile (4.43 ± 2.37% vs. 4.61 ± 1.97% vs. 5.20 ± 2.52% respectively, P = 0.03). Patients in the highest tertile of Lp-PLA2 values had significantly higher AIx values (24.65 ± 8.69% vs. 23.33 ± 9.65%, P = 0.03), in comparison to the lowest tertile, with Lp-PLA2 values < 101 μg/L. A linear regression analysis showed that Lp-PLA2 values > 138 μg/L negatively correlated to FMD [b = - 0.45 (95% CI: - 0.79 - -0.11), P = 0.01] and AIx values [b = 1.81 (95% CI: 0.57-3.05), P < 0.001] independently of cofounders like gender, age, diabetes mellitus, arterial hypertension, dyslipidemia, smoking habits, family history of CAD, history of previous myocardial infarction, serum glucose, circulating lipid levels, duration of CAD, antihypertensive medication, antidiabetic drugs, statin therapy and treatment with β-blockers.ConclusionsElevated Lp-PLA2 levels relate to endothelial dysfunction and arterial stiffness in patients with stable CAD independently from classical risk factors for CAD, statin use, antihypertensive treatment, and duration of the disease.

Project description:Background/objectivesElevated low-density lipoprotein cholesterol (LDL-C) in early adulthood is associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). The strength of the association between LDL-C and ASCVD among older adults, however, is less understood.DesignWe examined individual-level cohort data from the National Institutes of Health Pooled Cohorts (Framingham Study, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Cardiovascular Health Study), which prospectively measured CVD risk factors and incident disease.SettingProspective cohort study.ParticipantsAdults, aged 75 years or older, free of ASCVD.MeasurementsWe evaluated the associations between LDL-C and incident ASCVD (stroke, myocardial infarction, and cardiovascular death) in unadjusted analysis and in multivariable-adjusted Cox proportional hazards models. We assessed 5-year Kaplan-Meier ASCVD event rates in patients with and without hyperlipidemia (LDL-C ≥130 mg/dL or on lipid-lowering medications), stratified by the number of other risk factors, including smoking, diabetes, and hypertension.ResultsWe included 2667 adults, aged 75 years or older (59% female), free of ASCVD; median age was 78 years, with median LDL-C of 117 mg/dL. In both unadjusted and adjusted analyses, there was no association between LDL-C and ASCVD (adjusted hazard ratio = 1.022; 95% confidence interval = 0.998-1.046; P = .07). Among adults without other risk factors (free of smoking, diabetes, and hypertension), event rates were similar between those with and without hyperlipidemia (Kaplan-Meier rates = 5.8% and 7.0%, respectively). Among adults with one or two or more other risk factors, the presence of hyperlipidemia was also not associated with 5-year CVD event rates (Kaplan-Meier rates = 12.8% vs 15.0% [P = .44] for one other risk factor and 21.9% vs 24.0% [P = .59] for two or more other risk factors).ConclusionAmong a well-characterized cohort, LDL-C was not associated with CVD risk among adults aged 75 years or older, even in the presence of other risk factors. J Am Geriatr Soc 67:2560-2567, 2019.

Dataset Information

Lipoprotein-Associated Phospholipase A2 and Incident Peripheral Arterial Disease in Older Adults: The Cardiovascular Health Study.

Publications

Lipoprotein-Associated Phospholipase A2 and Incident Peripheral Arterial Disease in Older Adults: The Cardiovascular Health Study.

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