Cholesterol Efflux Capacity Associates with the Ankle-Brachial Index but Not All-Cause Mortality in Patients with Peripheral Artery Disease.
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ABSTRACT: Background
Cholesterol efflux is an important mechanism by which high-density lipoproteins (HDLs) protect against cardiovascular disease. As peripheral artery disease (PAD) is associated with high mortality rates, mainly due to cardiovascular causes, we investigated whether cholesterol efflux capacity (CEC) of apolipoprotein B (apoB)-depleted plasma, a widely used surrogate of HDL function, may serve as a predictive marker for mortality in this patient population.Methods
In this prospective single-center study (median follow-up time: 9.3 years), apoB-containing lipoproteins were precipitated from plasma of 95 patients with PAD and incubated with J744-macrophages, which were loaded with radiolabeled cholesterol. CEC was defined as the fractional radiolabel released during 4 h of incubation.Results
Baseline CEC was lower in PAD patients that currently smoked (p = 0.015) and had a history of myocardial infarction (p = 0.011). Moreover, CEC showed a significant correlation with HDL-cholesterol (p = 0.003) and apolipoprotein A-I levels (p = 0.001) as well as the ankle-brachial index (ABI, p = 0.018). However, CEC did not differ between survivors and non-survivors. Neither revealed Kaplan-Meier and Cox regression analyses any significant association of CEC with all-cause mortality rates.Conclusion
Taken together, CEC is associated with ABI but does not predict all-cause mortality in patients with PAD.
SUBMITTER: Clemens RK
PROVIDER: S-EPMC8394478 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background Lower ankle-brachial index (ABI) values within the 0.90 to 1.40 range are associated with poorer mitochondrial oxidative capacity of thigh muscles in cross-sectional analyses. Whether ABI decline is associated with greater declines in thigh muscle oxidative capacity with aging is unknown. Method and Results We analyzed data from 228 participants (100 men) of the BLSA (Baltimore Longitudinal Study of Aging), aged 39 to 97 years, with an ABI between 0.9 and 1.40 at baseline and at follow-up (mean follow-up period of 2.8 years). We examined mitochondrial oxidative capacity of the left thigh muscle, by measuring the postexercise phosphocreatine recovery rate constant (kPCr) from phosphorus-31 magnetic resonance spectroscopy. Greater kPCr indicated higher mitochondrial oxidative capacity. Although kPCr was available on the left leg only, ABI was measured in both legs. Longitudinal rates of change (Change) of left and right ABI and kPCr of the left thigh muscle were estimated using linear mixed effects models, and their association was analyzed by standardized multiple linear regressions. In multivariate analysis including sex, age, baseline kPCr, both left and right baseline ABI, and ABI change in both legs, (kPCr)Change was directly associated with ipsilateral (left) (ABI)Change (standardized [STD]-β=0.14; P=0.0168) but not with contralateral (right) (ABI)Change (P=0.22). Adjusting for traditional cardiovascular risk factors, this association remained significant (STD-β=0.18; P=0.0051). (kPCr)Change was steeper in White race participants (STD-β=0.16; P=0.0122) and body mass index (STD-β=0.13; P=0.0479). There was no significant association with current smoking status (P=0.63), fasting glucose (P=0.28), heart rate (P=0.67), mean blood pressure (P=0.78), and low-density lipoprotein (P=0.75), high-density lipoprotein (P=0.82), or triglycerides (P=0.15). Conclusions In people without peripheral arterial disease, greater decline in ABI over time, but not baseline ABI, was associated with faster decline in thigh mitochondrial oxidative capacity in the ipsilateral leg. Further studies are needed to examine whether early interventions that improve lower extremity muscle perfusion can improve and prevent the decline of muscle energetics.
| S-EPMC9075330 | biostudies-literature
Project description:ObjectivesAnkle-brachial index (ABI) is an independent prognostic marker of cardiovascular events among patients with coronary artery disease (CAD). We aimed to investigate the outcome of patients hospitalized with acute coronary syndrome (ACS) and abnormal ABI.Approach and resultsABI was prospectively measured in 1,047 patients hospitalized due to ACS, who were stratified into three groups, namely, those with clinical peripheral artery disease (PAD) (N = 132), those without clinical PAD but with abnormal (< 0.9) ABI (subclinical PAD; N = 148), and those without clinical PAD with normal ABI (no PAD; N = 767). Patients were prospectively followed for 30-day major adverse cardiovascular event (MACE) and 1-year all-cause mortality. The mean age was 64 years. There was a significant gradual increase throughout the three groups in age, i.e., the incidence of prior stroke, diabetes mellitus, and hypertension (p for trend = 0.001 for all). The in-hospital course showed a gradual rise in the incidence of complications with an increase in heart failure [2.5, 6.1, and 9.2%, (p for trend = 0.001)] and acute kidney injury [2, 4.1, and 11.5%, (p for trend = 0.001)]. At day 30, there was a stepwise increase in MACE, such that patients without PAD had the lowest rate, followed by subclinical and clinical PADs (3.5, 6.8, and 8.1%, respectively, p for trend = 0.009). Similarly, there was a significant increase in 1-year mortality from 3.4% in patients without PAD, through 6.8% in those with subclinical PAD, to 15.2% in those with clinical PAD (p for trend = 0.001).ConclusionSubclinical PAD is associated with poor outcomes in patients with ACS, suggesting that routine ABI screening could carry important prognostic significance in these patients regardless of PAD symptoms.
| S-EPMC9485724 | biostudies-literature
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| S-EPMC8031290 | biostudies-literature
Project description:Background There are no available lifetime risk estimates of lower-extremity peripheral artery disease (PAD). Methods and Results Using data from 6 US community-based cohorts and the vital statistics, we estimated the prevalence and incidence of PAD, defined as an ankle-brachial index < 0.90, at each year of age from birth to 80 years for white, black, and Hispanic men and women. Then, we used Markov Monte Carlo simulations in a simulated cohort of 100 000 individuals to estimate lifetime risk of PAD. On the basis of odds ratios of PAD for traditional atherosclerotic risk factors (eg, diabetes mellitus and smoking), we developed a calculator providing residual lifetime risk of PAD. In an 80-year horizon, lifetime risks of PAD were 30.0% in black men and 27.6% in black women, but ≈19% in white men and women and ≈22% in Hispanic men and women. From another perspective, 9% of blacks were estimated to develop PAD by 60 years of age, while the same proportion was seen at ≈70 years for whites and Hispanics. The residual lifetime risk within the same race/ethnicity varied by 3.5- to 5-fold according to risk factors (eg, residual lifetime risk in 45-year-old black men was 19.9% when current smoking, diabetes mellitus, and history of cardiovascular disease were absent versus 70.4% when all were present). Conclusions In the United States, ≈30% of blacks are estimated to develop PAD during their lifetime, whereas the corresponding estimate is ≈20% for whites and Hispanics. The residual lifetime risk within the same race/ethnicity substantially varies according to traditional risk factors.
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Project description:Peripheral artery tonometry (PAT) is a novel method for assessing arterial stiffness of small digital arteries. Pulse pressure can be regarded as a surrogate of large artery stiffness. When ankle-brachial index (ABI) is calculated using the higher of the two ankle systolic pressures as denominator (ABI-higher), leg perfusion can be reliably estimated. However, using the lower of the ankle pressures to calculate ABI (ABI-lower) identifies more patients with isolated peripheral arterial disease (PAD) in ankle arteries. We aimed to compare the ability of PAT, pulse pressure, and different calculations of ABI to detect atherosclerotic disease in lower extremities. We examined PAT, pulse pressure, and ABI in 66 cardiovascular risk subjects in whom borderline PAD (ABI 0.91 to 1.00) was diagnosed 4 years earlier. Using ABI-lower to diagnose PAD yielded 2-fold higher prevalence of PAD than using ABI-higher. Endothelial dysfunction was diagnosed in 15/66 subjects (23%). In a bivariate correlation analysis, pulse pressure was negatively correlated with ABI-higher (r = -0.347, p = 0.004) and with ABI-lower (r = -0.424, p < 0.001). PAT hyperemic response was not significantly correlated with either ABI-higher (r = -0.148, p = 0.24) or with ABI-lower (r = -0.208, p = 0.095). Measurement of ABI using the lower of the two ankle pressures is an efficient method to identify patients with clinical or subclinical atherosclerosis and worth performing on subjects with pulse pressure above 65 mm Hg. The usefulness of PAT measurement in detecting PAD is vague.
| S-EPMC3331653 | biostudies-other
Project description:BackgroundAnkle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) are both important indicators of arterial stiffness and vascular injury. At present, most studies on the relationship between ABI and baPWV and all-cause mortality in community-based elderly are analyzing ABI or baPWV alone, and will focus on a single special population such as diabetes and stroke. The purpose of this study was to evaluate the relationship between ABI and baPWV in a Chinese community-based elderly population, and to analyze their impact on all-cause mortality in a community-based population through a follow-up of nearly 10 years.MethodsParticipants were residents of the Wanshou Road community in Beijing, China. A total of 2,162 people in the community were included, with an average age of 71.48 years. During a mean follow-up period of 9.87 years, 1,826 subjects completed follow-up. Kaplan-Meier survival analysis and different Cox regression models were used to verify the association of ABI and baPWV with all-cause mortality. The selected subjects were divided into two groups according to ABI and baPWV, and ABI was divided into two groups with 0.90 as the cut-off point (group 1: 0.9 < ABI ≤ 1.3; group 2: ABI ≤ 0.9); according to the level of baPWV, they were divided into three groups (Tertile 1: baPWV <1761.5 cm/s; Tertile 2: 1761.5 ≤ baPWV <2121.5 cm/s; Tertile 3: baPWV ≥2121.5 cm/s).Results1,826 people were included in the statistical analysis, and the total mortality rate was 181.3/1000. The 10-year all-cause mortality rate of the abnormal ABI group (group 2) was 44.7%, and that of the normal ABI group (group 1) was 17.0%; The 10-year all-cause mortality rates from low to high in the baPWV tertile were 10.0%, 18.7%, and 26.4%. In the Cox proportional hazards model, after adjusting for possible confounders, the effect of baPWV on all-cause mortality was significant, with the 3rd tertile having a 1.647-fold higher risk of all-cause mortality than the 1st tertile (P = 0.014 ).ConclusionsABI and baPWV are risk factors affecting all-cause mortality in the elderly community population, and baPWV is an independent predictor of all-cause mortality in the elderly community population.
| S-EPMC9513615 | biostudies-literature
Project description:Background:The ankle-brachial index (ABI) and pulse wave velocity (PWV) are indices of atherosclerosis and arterial stiffness. The Japan-made measuring devices of those indices have spread widely because of their convenience and the significance of the parameters. However, studies that comprehensively discuss the various pitfalls in using these indices are not available. Methods:This study presents several representative pitfalls in using the ABI and brachial-ankle PWV (baPWV) by showing the result sheets of the device, "the Vascular Profiler". Furthermore, some considerations when utilizing these indices in the future are also discussed. Results:Several diseases such as arteriosclerosis obliterans (ASO), arterial calcification in the lower limb, arterial stenosis in the right upper-limb, aortic valve diseases, arterial stenosis in the upper-limb of the contralateral side of the hemodialysis access, are the representative pitfalls when evaluating ABI and baPWV. Moreover, a measurement error is found to actually exist. Furthermore, same phenomena are considered most likely to occur when using other similar indices and devices. Conclusion:The ABI and baPWV are the useful and significant biomarkers. Nevertheless, caution is sometimes necessary when interpreting them. Moreover, rigorous patient exclusion criteria should be considered when using those indices in the severely conditioned patient population. And the results of this study can be applied to enhance the literacy using other indices, such as the cardio-ankle vascular index and other similar devices.
| S-EPMC5892969 | biostudies-literature
Project description:BackgroundNon-invasive clinic-based tools for assessing PAD are not without limitations. Therefore, costly tests like Doppler study, CT angiography and MR angiography are often required to make a diagnosis. Ankle brachial index (ABI), commonly used for assessment of PAD, has high false positivity rates in sclerosed, calcified arteries which render them non-compressible. Toe brachial index (TBI) can be an alternative, as digital arteries are relatively unaffected by these changes.AimTo compare the reliability of ABI and TBI in diagnosing PAD in type 2 diabetes using CT angiography (CTA) as the reference.Methods175 adults with T2D were selected. ABI &TBI were measured with an automated vascular Doppler XT 6 ports bilaterally for all subjects. For any subject, the limb with lower ABI and TBI was included for analysis. ABI < 0.9 & TBI < 0.6 were taken as evidence of PAD. CTA showing > 50% narrowing was taken as evidence of PAD.Results24% of our study subjects had CTA confirmed PAD. ABI has low sensitivity of 35.29% (95% CI 0.21-0.52) compared to TBI being 82.35% (95% CI 0.66-0.92). The specificity however was similar. ABI < 0.9 was able to detect CTA confirmed PAD, but ABI > 0.9, including the so-called normal ABI (0.9-1.3) was unable to detect PAD. ROC showed ABI at 1.005 has sensitivity 64.71% (95% CI 0.48- 0.79) and specificity 61.7% (95% CI 0.53-0.69) and TBI at 0.6 has sensitivity 82.35% (95% CI 0.66-0.92) & specificity 92% (95% CI 0.87-0.96). Utilizing Cohen's Kappa, the reliability of ABI with respect to CTA showed fair agreement (K = 0.225, p = 0.001), whereas the reliability of TBI with respect to CTA showed substantial agreement (K = 0.759, p < 0.0001).ConclusionABI < 0.9 detects PAD reliably, but presence of PAD in patients with ABI > 9.0 including the normal of ABI (0.9-1.3) can be confirmed with TBI, which correlated strongly with CTA. TBI is also non-inferior for PAD detection, when ABI < 0.9. TBI and not ABI can be utilized for initial assessment of PAD in subjects with T2D.
| S-EPMC10898040 | biostudies-literature
Project description:OBJECTIVE:This study investigated the effects of garlic on brachial endothelial function and THP-1 macrophage cholesterol efflux (CE) and examined whether garlic modulates ATP-binding cassette (ABC) A1 and ABCG1 mRNA expressions in peripheral blood mononuclear cells (PBMCs) isolated from patients with coronary artery disease (CAD). METHODS:In this randomized, placebo-controlled trial, patients with CAD were randomly divided into two groups: those receiving garlic powder or placebo tablets twice daily for 3 months. Brachial flow-mediated dilation (FMD) was assessed using ultrasound. Fasting blood samples were collected before and after period and PBMC and plasma were isolated. Human THP-1 monocytes were differentiated into macrophages, labeled with 3H-cholesterol, and incubated with plasma samples, and CE was assessed. ABCA1 and ABCG1 mRNA expressions were determined in PBMCs. RESULTS:After 3 months, brachial FMD values significantly improved (50.7%) in the garlic group compared with those in the placebo group (p=0.016). High-sensitive C-reactive protein (hs-CRP) levels significantly decreased in the garlic group, but the difference between the two groups was not statistically significant. No significant difference was observed with regard to CE and ABCA1 and ABCG1 mRNA expressions in PBMCs. CE was negatively correlated with hs-CRP levels. CONCLUSION:Short-term treatment with garlic may improve the endothelial function and may affect hs-CRP levels; however, it could neither significantly improve THP-1 macrophage CE nor affect ABCA1 or ABCG1 expressions in PBMCs.
| S-EPMC5731260 | biostudies-literature
Project description:Ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) are used as non-invasive indicators for detecting atherosclerosis and arterial stiffness, two well-known predictors of mortality in patients with type 2 diabetes mellitus (T2DM). ABI and baPWV have independent associations with mortality; however, their joint and interactive effects on mortality have not been assessed in patients with T2DM. This work aims to evaluate the independent, joint, and interactive associations of ABI and baPWV with all-cause and expanded cardiovascular disease (CVD) mortality in patients with T2DM. This observational study included 2160 patients with T2DM enlisted in the Diabetes Care Management Program database of China Medical University Hospital from 2001 to 2016 and then followed their death status until August 2021. Cox proportional hazard models were used to evaluate the independent, joint, and interactive effects of ABI and baPWV on the risk of all-cause and expanded CVD mortality. A total of 474 patient deaths occurred after a mean follow-up of 8.4 years, and 268 of which were attributed to cardiovascular events. Abnormal ABI (≤ 0.9) and highest baPWV quartile were independently associated with increased risks of all-cause [ABI: hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.30-2.11; baPWV: 1.63, 1.16-2.27] and expanded CVD mortality (ABI: 2.21, 1.62-3.02; baPWV: 1.75, 1.09-2.83). The combination of abnormal ABI (≤ 0.9) and highest baPWV quartile was associated with a significantly higher risk of all-cause (4.51, 2.50-8.11) and expanded CVD mortality (9.74, 4.21-22.51) compared with that of the combination of normal ABI and lowest baPWV quartile. Significant interactions were observed between ABI and baPWV in relation to all-cause and expand CVD mortality (both p for interaction < 0.001). Through their independent, joint, and interactive effects, ABI and baPWV are significant parameters that can improve the prediction of all-cause and expanded CVD mortality in patients with T2DM and help identify high-risk patients who may benefit from diabetes care.
| S-EPMC9247028 | biostudies-literature