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: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.
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Project description:BackgroundThe postexercise ankle-brachial index (ABI) is useful in patients with suspected peripheral arterial disease (PAD) and a normal resting ABI. Our objective was to determine the independent predictors of an abnormal postexercise ABI.HypothesisWe hypothesized that the lowest ankle systolic pressure to calculate the resting ABI would be associated with an abnormal post-exercise ABI.MethodsAmong 619 consecutive patients referred for suspected PAD, we calculated the postexercise ABI in patients with a normal resting ABI. An ABI <0.90 at rest was considered abnormal. We investigated 3 definitions of an abnormal postexercise ABI, defined as either <0.90, or >5% or >20% reduction compared with rest.ResultsUsing multivariate analysis, the lowest ABI (calculated using the lowest and not the highest ankle systolic pressure) was consistently the most powerful independent predictor of an abnormal postexercise ABI. Patients with an abnormal lowest resting ABI were significantly more likely to have an abnormal postexercise ABI, as well as a significantly greater reduction in the ABI compared with rest. The lowest ABI had a high specificity (95%) but low sensitivity (82%) for a postexercise ABI <0.90.ConclusionsAn abnormal lowest ABI (calculated with the lowest ankle systolic pressure) is the most important independent predictor of an abnormal ABI response to exercise in patients with a conventionally normal ABI. All such patients should be exercised and their ABI measured postexercise.
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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.
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Project description:BACKGROUND:Ankle-brachial index (ABI), the first-line diagnostic test for peripheral artery disease, can be falsely elevated when ankle arteries are incompressible, showing a J-shaped association with mortality. In this situation, toe-brachial index (TBI) is the recommended test. However, whether TBI provides additional prognostic information beyond ABI in patients on hemodialysis is unknown. METHODS:In this retrospective cohort study of 247 Japanese prevalent hemodialysis patients (mean age 66.8 [SD 11.6] years), we evaluated mortality (116 deaths over a median follow-up of 5.2?years) related to quartiles of ABI and TBI, as well as three categories of low ABI (?0.9), normal/high ABI (>?0.9)?+?low TBI (?0.6), and normal/high ABI?+?normal TBI (>?0.6) using multivariable Cox models. RESULTS:ABI showed a J-shaped association with mortality (adjusted hazard ratio 2.72 [95% CI, 1.52-4.88] in the lowest quartile and 1.59 [95% CI, 0.87-2.90] in the highest quartile vs. the second highest). Lower TBI showed a potentially dose-response association with mortality (e.g., adjusted hazard ratios 2.63 [95% CI, 1.36-5.12] and 2.89 [95% CI, 1.49-5.61] in the lowest two quartiles vs. the highest). When three categories by both ABI and TBI were analyzed, those with low ABI (?0.9) experienced the highest risk followed by normal/high ABI (>?0.9)?+?low TBI (?0.6). Among patients with normal/high ABI (>?0.9), the increased mortality risk in individuals with low TBI (?0.6) compared to those with normal TBI (>?0.6) were significant (adjusted hazard ratio 1.84 [95% CI, 1.12-3.02]). CONCLUSIONS:Lower TBI was independently associated with mortality in patients on hemodialysis and has the potential to classify mortality risk in patients with normal/high ABI. Our results support the importance of evaluating TBI in addition to ABI in this clinical population.
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Project description:Introduction: We investigated whether the toe-brachial index (TBI) is associated with stroke prognosis and evaluated this association in patients with normal ankle-brachial index (ABI). Methods: Acute ischemic stroke patients who underwent TBI measurements were enrolled. Poor functional outcome was defined as modified Rankin Scale score ≥3. Major adverse cardiovascular event (MACE) was defined as stroke recurrence, myocardial infarction, or death. Normal ABI was defined as 0.9 ≤ ABI ≤ 1.4. Results: A total of 1,697 patients were enrolled and followed up for a median 39.7 (interquartile range, 25.7-54.6) months. During the period, 305 patients suffered MACE (18.0%), including 171 (10.1%) stroke recurrences. TBI was associated with hypertension, diabetes, atrial fibrillation, aortic plaque score, ABI, and brachial-ankle pulse wave velocity (all p < 0.05). In multivariable logistic regression, TBI was inversely associated with poor functional outcome in all patients [odds ratio (OR) 0.294, 95% confidence interval (CI) 0.114-0.759], even in patients with normal ABI (OR 0.293, 95% CI 0.095-0.906). In multivariable Cox regression, TBI < 0.6 was associated with stroke recurrence [hazard ratio (HR) 1.651, 95% CI 1.135-2.400], all-cause mortality (HR 2.105, 95% CI 1.343-3.298), and MACE (HR 1.838, 95% CI 1.396-2.419) in all patients. TBI < 0.6 was also associated with stroke recurrence (HR 1.681, 95% CI 1.080-2.618), all-cause mortality (HR 2.075, 95% CI 1.180-3.651), and MACE (HR 1.619, 95% CI 1.149-2.281) in patients with normal ABI. Conclusions: Low TBI is independently associated with poor short- and long-term outcomes in acute ischemic stroke patients despite normal ABI.
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