Background. Atherothrombotic disease, including coronary artery disease (CAD) and peripheral artery disease (PAD), can lead to cardiovascular (CV) events, such as myocardial infarction, stroke, limb ...ischemia, heart failure, and CV death. Aim. Evaluate the humanistic and economic burden of CAD and PAD and identify unmet needs through a comprehensive literature review. Methods. Relevant search terms were applied across online publication databases. Studies published between January 2010 and August 2017 meeting the inclusion/exclusion criteria were selected; guidelines were also included. Two rounds of screening were applied to select studies of relevance. Results. Worldwide data showed approximately 5–8% prevalence of CAD and 10–20% prevalence of PAD, dependent on the study design, average age, gender, and geographical location. Data from the REACH registry indicated that 18–35% of patients with CAD and 46–68% of patients with PAD had disease in one or more vascular beds. Use of medication to control modifiable CV risk factors was variable by country (lower in France than in Canada); statins and aspirin were the most widely used therapies in patients with chronic disease. Survival rates have improved with medical advancements, but there is an additional need to improve the humanistic burden of disease (i.e., associated disability and quality of life). The economic burden of atherothrombotic disease is high and expected to increase with increased survival and the aging population. Conclusion. CAD and PAD represent a substantial humanistic and economic burden worldwide, highlighting a need for new interventions to reduce the incidence of atherothrombotic disease.
Neutrophil-lymphocyte ratio (NLR) has been associated with inferior outcomes after lower extremity interventions. NLR has been associated with systemic inflammation and atherosclerotic burden. We ...examined NLR, severity of peripheral artery disease (PAD), and outcomes after endovascular or open surgical procedures.
Inpatients undergoing lower extremity procedures (2008-2016) were selected from Cerner Health Facts database (Cerner Corporation, North Kansas City, Mo) using International Classification of Diseases, Ninth Revision procedure codes. Disease severity was grouped into claudication, rest pain, and tissue loss. Outcomes were identified using International Classification of Diseases, Ninth Revision codes. NLR was calculated preoperatively and postoperatively. A χ2 analysis and multivariable logistic regression were performed. A receiver operating characteristic curve analysis was used to determine the cutoff for preoperative (low, <3.65; high, ≥3.65) and postoperative (low, <5.96; high, ≥5.96) NLR values.
There were 3687 patients evaluated; 2183 (59%) underwent endovascular procedures and 1504 (41%) had open procedures. Compared with black patients, claudication was more frequent in white patients (81.7% vs 72.7%; P < .0001), and tissue loss was less common (12.9% vs 20.9%; P < .0001). NLR values were higher for patients with tissue loss than for patients with rest pain or claudication (4.89, 4.33, and 3.11, respectively; P < .0001). Open procedures were associated with higher postoperative NLR values than endovascular procedures (6.8 vs 5.2; P < .0001). Mean preoperative and postoperative NLR values were greater in patients with more severe PAD. Multivariable analysis demonstrated that preoperative high NLR was strongly associated with in-hospital death (odds ratio OR, 5.4; 95% confidence interval CI, 1.68-17.07), cardiac complications (OR, 2.9; 95% CI, 1.57-5.40), amputation (OR, 2.5; 95% CI, 1.65-3.87), renal failure (OR, 1.9; 95% CI, 1.18-2.93), respiratory complications (OR, 1.7; 95% CI, 1.09-2.76), and prolonged length of stay (OR, 1.9; 95% CI, 1.89-3.71).
Preoperative and postoperative NLR significantly increases with disease severity for PAD, providing further evidence of NLR as a biomarker of a patient's systemic inflammatory state. After adjustment for confounders, NLR still remained strongly associated with death and other adverse outcomes after intervention for PAD. Further study of the clinical association of NLR with other vascular disorders, such as symptomatic carotid stenosis and symptomatic and ruptured aortic aneurysmal disease, is planned to guide individualized treatment to prevent stroke or aneurysm rupture.
Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines with recommendations to improve ...cardiovascular health. These guidelines, based on systematic methods to evaluate and classify evidence, provide a cornerstone of quality cardiovascular care.
In response to reports from the Institute of Medicine
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and a mandate to evaluate new knowledge and maintain relevance at the point of care, the ACC/AHA Task Force on Clinical Practice Guidelines (Task Force) modified its methodology.
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The relationships among guidelines, data standards, appropriate use criteria, and performance measures are addressed elsewhere.
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RATIONALE:Critical limb ischemia is a life-threatening complication of peripheral arterial disease. In patients who are ineligible for revascularization procedures, there are few therapeutic ...alternatives, leading to amputations and death.
OBJECTIVE:To provide a systematic review of the literature and a meta-analysis of studies evaluating safety and efficacy of autologous cell therapy for intractable peripheral arterial disease/critical limb ischemia.
METHODS AND RESULTS:We retrieved 19 randomized controlled trials (837 patients), 7 nonrandomized trials (338 patients), and 41 noncontrolled studies (1177 patients). The primary outcome was major amputation. Heterogeneity was high, and publication bias could not be excluded. Despite these limitations, the primary analysis (all randomized controlled trials) showed that cell therapy reduced the risk of amputation by 37%, improved amputation-free survival by 18%, and improved wound healing by 59%, without affecting mortality. Cell therapy significantly increased ankle brachial index, increased transcutaneous oxygen tension, and reduced rest pain. The secondary analysis (all controlled trials; n=1175 patients) shows that there may be potential to avoid ≈1 amputation/year for every 2 patients successfully treated. The tertiary analysis (all studies; n=2332 patients) precisely estimated the changes in ankle brachial index, transcutaneous oxygen tension, rest pain, and walking capacity after cell therapy. Intramuscular implantation appeared more effective than intra-arterial infusion, and mobilized peripheral blood mononuclear cells may outperform bone marrow–mononuclear cells and mesenchymal stem cells. Amputation rate was improved more in trials wherein the prevalence of diabetes mellitus was high. Cell therapy was not associated with severe adverse events. Remarkably, efficacy of cell therapy on all end points was no longer significant in placebo-controlled randomized controlled trials and disappeared in randomized controlled trials with a low risk of bias.
CONCLUSIONS:Although this meta-analysis highlights the need for more high-quality placebo-controlled trials, equipoise may no longer be guaranteed because autologous cell therapy has the potential to modify the natural history of intractable critical limb ischemia.
With a rise in the aging popluation, the prevalence of peripheral arterial disease (PAD) is markedly increasing. The overall disease prevalence of PAD is in the range of 3%-10%, which increases to ...15%-20% in persons older than 70 years of age. Given this upward trend in disease prevalence, the economic and societal burden of PAD would be considerable. The subgroup of patients who develop critical limb ischemia (CLI) represents the most challenging population to manage medically, surgically, and endovascularly. Patients with symptomatic PAD and CLI have an increased risk for death and cardiovascular events, especially in those with CLI who carry with them a substantial risk of limb loss. Advances in medical, surgical, and endovascular techniques have shown excellent outcomes in the treatment of these patients, however the optimal management paradigm has not been elucidated. This article reviews the classification and epidemiology, risk factors, natural history, and health care costs associated with PAD and CLI.
OBJECTIVE:Inflammatory markers, such as hs-CRP (high-sensitivity C-reactive protein), have been reported to be related to peripheral artery disease (PAD). Galectin-3, a biomarker of fibrosis, has ...been linked to vascular remodeling and atherogenesis. However, its prospective association with incident PAD is unknown; as is the influence of inflammation on the association between galectin-3 and PAD.
APPROACH AND RESULTS:In 9851 Atherosclerosis Risk in Communities Study participants free of PAD at baseline (1996–1998), we quantified the association of galactin-3 and hs-CRP with incident PAD (hospitalizations with PAD diagnosis International Classification of Diseases-Ninth Revision440.2–440.4 or leg revascularization eg, International Classification of Diseases-Ninth Revision38.18) as well as its severe form, critical limb ischemia (PAD cases with resting pain, ulcer, gangrene, or leg amputation) using Cox models. Over a median follow-up of 17.4 years, there were 316 cases of PAD including 119 critical limb ischemia cases. Log-transformed galectin-3 was associated with incident PAD (adjusted hazard ratio, 1.17 1.05–1.31 per 1 SD increment) and critical limb ischemia (1.25 1.05–1.49 per 1 SD increment). The association was slightly attenuated after further adjusting for hs-CRP (1.14 1.02–1.27 and 1.22 1.02–1.45, respectively). Log-transformed hs-CRP demonstrated robust associations with PAD and critical limb ischemia even after adjusting for galectin-3 (adjusted hazard ratio per 1 SD increment 1.34 1.18–1.52 and 1.34 1.09–1.65, respectively). The addition of galectin-3 and hs-CRP to traditional atherosclerotic predictors (C statistic of the base model 0.843 0.815–0.871) improved the risk prediction of PAD (ΔC statistics, 0.011 0.002–0.020).
CONCLUSIONS:Galectin-3 and hs-CRP were independently associated with incident PAD in the general population, supporting the involvement of fibrosis and inflammation in the pathophysiology of PAD.
Objective/Background Critical limb ischemia (CLI) is the most advanced stage of peripheral artery disease (PAD), and many patients with CLI are not eligible for conventional revascularization. In the ...last decade, cell based therapies have been explored as an alternative treatment option for CLI. A meta-analysis was conducted of randomized placebo controlled trials investigating bone marrow (BM) derived cell therapy in patients with CLI. Methods The MEDLINE, Embase, and the Cochrane Controlled Trials Register databases were systematically searched, and all included studies were critically appraised by two independent reviewers. The meta-analysis was performed using a random effects model. Results Ten studies, totaling 499 patients, were included in this meta-analysis. No significant differences were observed in major amputation rates (relative risk RR 0.91; 95% confidence interval CI 0.65–1.27), survival (RR 1.00; 95% CI 0.95–1.06), and amputation free survival (RR 1.03; 95% CI 0.86–1.23) between the cell treated and placebo treated patients. The ankle brachial index (mean difference 0.11; 95% CI 0.07–0.16), transcutaneous oxygen measurements (mean difference 11.88; 95% CI 2.73–21.02), and pain score (mean difference –0.72; 95% CI –1.37 to –0.07) were significantly better in the treatment group than in the placebo group. Conclusions This meta-analysis of placebo controlled trials showed no advantage of stem cell therapy on the primary outcome measures of amputation, survival, and amputation free survival in patients with CLI. The potential benefit of more sophisticated cell based strategies should be explored in future randomized placebo controlled trials.
It has been reported that the triglyceride-glucose (TyG) index may serve as a simple and credible surrogate marker of insulin resistance (IR). However, its association with macrovascular and ...microvascular damage is unclear. Accordingly, the objective of the present study is to investigate the association of macrovascular and microvascular damage with the TyG index.
A total of 2830 elderly participants from the Northern Shanghai Study (NSS) were enrolled. The TyG index was calculated as lnfasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2. Parameters of vascular damage, including carotid-femoral pulse wave velocity (cf-PWV), brachial-ankle pulse wave velocity (ba-PWV), ankle-brachial index (ABI), carotid intima-media thickness (CMT), carotid plaque, estimated glomerular filtration rate (eGFR) and the urine albumin-to-creatinine ratio (UACR), were measured and calculated.
In univariate logistic regression, an increased TyG index was associated with a higher risk of cf-PWV > 10 m/s, ba-PWV > 1800 cm/s, ABI < 0.9, microalbuminuria (MAU) and chronic kidney disease (CKD). In multivariable logistic regression, there was a significant increase in the risk of cf-PWV > 10 m/s (OR = 1.86, 95% confidence interval 95% CI 1.37-2.53, P
< 0.001), ba-PWV > 1800 cm/s (OR = 1.39, 95% CI 1.05-1.84, P
= 0.02), MAU (OR = 1.61, 95% CI 1.22-2.13, P
< 0.001) and CKD (OR = 1.67, 95% CI 1.10-1.50, P
= 0.02) after adjustment for age, sex, BMI, waist circumference, smoking habit, hypertension, family history of premature CVD, diabetes, HDL-C, LDL-C, insulin therapy and statin therapy. However, no significant relationship was observed between the TyG index and lower extremity atherosclerosis, carotid hypertrophy or carotid plaque.
An elevated TyG index was significantly associated with a higher risk of arterial stiffness and nephric microvascular damage. This conclusion lends support to the clinical significance of the TyG index for the assessment of vascular damage.
The aim of our study was to determine the incidence, characteristics, and clinical outcomes of patients with the novel coronavirus (COVID-19) infection who had presented with and been treated for ...acute limb ischemia (ALI) during the 2020 coronavirus pandemic.
We performed a single-center, observational cohort study. The data from all patients who had tested positive for COVID-19 and had presented with ALI requiring urgent operative treatment were collected in a prospectively maintained database. For the present series, successful revascularization of the treated arterial segment was defined as the absence of early (<30 days) re-occlusion or major amputation or death within 24 hours. The primary outcomes were successful revascularization, early (≤30 days) and late (≥30 days) survival, postoperative (≤30 days) complications, and limb salvage.
We evaluated the data from 20 patients with ALI who were positive for COVID-19. For the period from January to March, the incidence rate of patients presenting with ALI in 2020 was significantly greater than that for the same months in 2019 (23 of 141 16.3% vs 3 of 163 1.8%; P < .001). Of the 20 included patients, 18 were men (90%) and two were women (10%). Their mean age was 75 ± 9 years (range, 62-95 years). All 20 patients already had a diagnosis of COVID-19 pneumonia. Operative treatment was performed in 17 patients (85%). Revascularization was successful in 12 of the 17 (70.6%). Although successful revascularization was not significantly associated with the postoperative use of intravenous heparin (64.7% vs 83.3%; P = .622), no patient who had received intravenous heparin required reintervention. Of the 20 patients, eight (40%) had died in the hospital. The patients who had died were significantly older (81 ± 10 years vs 71 ± 5 years; P = .008). The use of continuous postoperative systemic heparin infusion was significantly associated with survival (0% vs 57.1%; P = .042).
In our preliminary experience, the incidence of ALI has significantly increased during the COVID-19 pandemic in the Italian Lombardy region. Successful revascularization was lower than expected, which we believed was due to a virus-related hypercoagulable state. The use of prolonged systemic heparin might improve surgical treatment efficacy, limb salvage, and overall survival.
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