Ehrin J. Armstrong

The association between psoriasis and hypertension: A systematic review and meta-analysis of observational studies

Population-based observational studies have suggested a relationship between psoriasis and hypertension. We performed a systematic review and meta-analysis to better understand the association between psoriasis and hypertension. We systematically searched MEDLINE, EMBASE, and the Cochrane Central Register from 1 January 1980 to 1 January 2012. Two authors independently assessed trial eligibility and quality. We applied the Meta-Analysis of Observational Studies in Epidemiology guidelines in the conduct of this study. We identified 24 observational studies with a total of approximately 2.7 million study participants fulfilling our inclusion criteria. Among them, 309 469 were patients with psoriasis. On the basis of random effects modeling of case–control and cross–sectional studies, the odds ratio (OR) for hypertension among patients with psoriasis was 1.58 [95% confidence interval (CI) 1.42–1.76] compared with the controls. The OR for hypertension among patients with mild psoriasis was 1.30 (95% CI 1.15–1.47) and the OR for hypertension among patients with severe psoriasis was 1.49 (95% CI 1.20–1.86) compared with the controls. Two cohort studies examining incidence of hypertension found that psoriasis was associated with a hazard ratio of 1.09 (95% CI 1.05–1.14) and 1.17 (95% CI 1.06–1.30) for development of hypertension. In a subgroup analysis, patients with psoriatic arthritis also had an increased prevalence of hypertension (OR 2.07, 95% CI 1.41–3.04). Psoriasis and psoriatic arthritis are associated with greater prevalence of hypertension. Patients with severe psoriasis have greater odds of hypertension than those with mild psoriasis.

Endothelial Dysfunction and the Effects of TNF Inhibitors on the Endothelium in Psoriasis and Psoriatic Arthritis: A Systematic Review

BACKGROUND Epidemiologic data support the association of psoriasis and psoriatic arthritis with adverse cardiovascular outcomes. Shared pathogenesis in endothelial dysfunction may underlie psoriasis and atherosclerosis. Tumor necrosis factor (TNF) inhibitors may modulate endothelial dysfunction seen in patients with psoriasis and psoriatic arthritis. OBJECTIVE To perform a systematic review that investigated endothelial function in psoriasis and psoriatic arthritis and the effect of TNF inhibitors on endothelial function in psoriasis and psoriatic arthritis. METHODS MEDLINE (1980-October 2012), Web of Science, the EULAR abstract database, and the AAD annual meeting abstract archive were searched for cross-sectional or longitudinal studies that 1) examined endothelial function in patients with psoriasis or psoriatic arthritis, or 2) investigated the effect of TNF inhibitor therapy on endothelial function. RESULTS Twenty articles and four abstracts with 2261 patients evaluated endothelial function in psoriasis and psoriatic arthritis, which was measured by pulse wave velocity, flow-mediated dilation, nitroglycerine-induced vasodilation, carotid intima-media thickness, peripheral arterial tonometry, or aortic stiffness parameters. The majority of the data suggests that patients with psoriasis and psoriatic arthritis have significantly increased arterial stiffness, impaired endothelial-dependent vasodilation, increased carotid intima-media thickness, and decreased aortic elasticity compared to the general population. Two out of three studies showed that TNF inhibitors improved endothelial function in psoriasis and psoriatic arthritis. LIMITATIONS Measurements of endothelial function were not standardized across studies. CONCLUSIONS The preponderance of literature suggests that endothelial function is significantly impaired in patients with psoriasis and psoriatic arthritis compared to the general population. Preliminary evidence suggests that TNF inhibitors may improve endothelial function in the psoriasis and psoriatic arthritis populations.

Pathogenesis of the Limb Manifestations and Exercise Limitations in Peripheral Artery Disease

Patients with peripheral artery disease have a marked reduction in exercise performance and daily ambulatory activity irrespective of their limb symptoms of classic or atypical claudication. This review will evaluate the multiple pathophysiologic mechanisms underlying the exercise impairment in peripheral artery disease based on an evaluation of the current literature and research performed by the authors. Peripheral artery disease results in atherosclerotic obstructions in the major conduit arteries supplying the lower extremities. This arterial disease process impairs the supply of oxygen and metabolic substrates needed to match the metabolic demand generated by active skeletal muscle during walking exercise. However, the hemodynamic impairment associated with the occlusive disease process does not fully account for the reduced exercise impairment, indicating that additional pathophysiologic mechanisms contribute to the limb manifestations. These mechanisms include a cascade of pathophysiological responses during exercise-induced ischemia and reperfusion at rest that are associated with endothelial dysfunction, oxidant stress, inflammation, and muscle metabolic abnormalities that provide opportunities for targeted therapeutic interventions to address the complex pathophysiology of the exercise impairment in peripheral artery disease.

Safety and Procedural Success of Left Atrial Appendage Exclusion With the Lariat Device: A Systematic Review of Published Reports and Analytic Review of the FDA MAUDE Database

IMPORTANCE The Lariat device has received US Food and Drug Administration (FDA) 510(k) clearance for soft-tissue approximation and is being widely used off-label for left atrial appendage (LAA) exclusion. A comprehensive analysis of safety and effectiveness has not been reported. OBJECTIVES To perform a systematic review of published literature to assess safety and procedural success, defined as successful closure of the LAA during the index procedure, of the Lariat device. We performed a formal analytic review of the FDA MAUDE (Manufacturer and User Facility Device Experience) database to compile adverse event reports from real-world practice with the Lariat. DATA SOURCES For the systematic review, PubMed, EMBASE, CINAHL, and the Cochrane Library were searched from January 2007 through August 2014 to identify all studies reporting use of the Lariat device in 3 or more patients. The FDA MAUDE database was queried for adverse events reports related to Lariat use. DATA EXTRACTIONS AND SYNTHESIS Data were abstracted in duplicate by 2 physician reviewers. Events from published literature were pooled using a generic inverse variance weighting with a random effects model. Cumulative and individual adverse events were also reported using the FDA MAUDE data set. MAIN OUTCOMES AND MEASURES Procedural adverse events and procedural success. RESULTS In the systematic review, 5 reports of Lariat device use in 309 participants were identified. Specific complications weighted for inverse of variance of individual studies were urgent need for cardiac surgery (2.3%; 7 of 309 procedures) and death (0.3%; 1 of 309 procedures). Procedural success was 90.3% (279 of 309 procedures). In the FDA MAUDE database, there were 35 unique reports of adverse events with use of the Lariat device. Among these, we identified 5 adverse event reports that noted pericardial effusion and death and an additional 23 reported urgent cardiac surgery without mention of death. CONCLUSIONS AND RELEVANCE This review of published reports and case reports identified risks of adverse events with off-label use of the Lariat device for LAA exclusion. Formal, controlled investigations into the safety and efficacy of the device for this indication are warranted.

Smoking cessation is associated with decreased mortality and improved amputation-free survival among patients with symptomatic peripheral artery disease

OBJECTIVE Although smoking cessation is recommended for all patients with peripheral artery disease, there are little data regarding the prevalence of smoking among patients at the time of angiography or the effect of smoking cessation on clinical outcomes. METHODS Consecutive patients with claudication or critical limb ischemia who underwent peripheral angiography from 2006 to 2013 were included in an observational cohort analysis. Smoking status was assessed at the time of angiography and during follow-up clinic visits. Kaplan-Meier analysis was used to assess the relationship between smoking cessation, mortality, and amputation-free survival. RESULTS Among 739 patients (423 men and 316 women; mean age, 60 ± 12 years), 204 (28%) remained active smokers at the time of lower extremity angiography. At the time of angiography, the mean number of cigarettes smoked per day was 16 ± 10, and the mean pack-years was 40 ± 25. During the course of the subsequent year, 61 patients (30%) successfully quit smoking and maintained continued abstinence. Baseline medication use between groups did not differ significantly. The mean ankle-brachial index was also similar for quitters vs nonquitters (0.53 ± 24 vs 0.49 ± 0.22; P = .3). During follow-up to 5 years, patients who quit smoking had significantly lower all-cause mortality (14% vs 31%; hazard ratio, 0.40; 95% confidence interval, 0.18-0.90) and improved amputation-free survival (81% vs 60%; hazard ratio, 0.43, 95% confidence interval, 0.22-0.86) compared with patients who continued smoking, with most of the difference driven by reduced mortality among patients who quit smoking. The findings remained significant on multivariable analysis. CONCLUSIONS Approximately one-third of active smokers with peripheral artery disease successfully quit smoking ≤ 1 year after lower extremity angiography. Patients who quit smoking have lower mortality and improved amputation-free survival compared with patients who continue smoking.

Effects of Biologic Agents and Other Disease-Modifying Antirheumatic Drugs on Cardiovascular Outcomes in Psoriasis and Psoriatic Arthritis: A Systematic Review

BACKGROUND Whether systemic treatments for psoriasis or psoriatic arthritis affect cardiovascular comorbidities is a clinically significant question. OBJECTIVE To examine the effects of biologic agents and other Disease-Modifying Antirheumatic Drugs (DMARDs) used to treat psoriasis and psoriatic arthritis on cardiovascular risk factors and adverse cardiovascular outcomes. METHODS MEDLINE (1980-October 2012), Web of Science, the EULAR abstract database, and the AAD annual meeting abstract archive were searched for studies evaluating biologic and other DMARD therapy for psoriasis and psoriatic arthritis that reported cardiovascular events as primary outcomes. RESULTS From 20 studies that met the search criteria for the review, 81,469 patients with psoriasis and/or psoriatic arthritis were included in the data synthesis of the current literature. While the data on the cardioprotective effect of methotrexate exist in patients with rheumatoid arthritis, its effect on the psoriasis and psoriatic arthritis populations with regards to cardiovascular outcomes are inconclusive at this time. The association of hypertension with long-term cyclosporine use prompts discontinuation of cyclosporine in selected patients. The use of TNF inhibitors may be associated with reduced risk of adverse cardiovascular events in preliminary epidemiologic studies; however, large randomized controlled trials and epidemiologic studies with well-characterized populations will be necessary to elucidate their exact effects. The short-term data regarding the safety of IL-12/23 inhibitors showed that, to date, there are no increased cardiovascular events compared to the general population. CONCLUSIONS To date, epidemiologic data is insufficient to reach definitive conclusions with regards to the effects of biologics and other DMARDs on cardiovascular outcomes in psoriasis and psoriatic arthritis patients. Adequately powered, long-term, controlled studies are necessary to determine the cardioprotective effects of TNF inhibitors observed in preliminary studies on psoriasis and psoriatic arthritis populations.

Nitinol Self-Expanding Stents vs. Balloon Angioplasty for Very Long Femoropopliteal Lesions

Purpose To compare the patency rates and clinical outcomes of balloon angioplasty vs. nitinol stent placement for patients with short (≤150 mm) as compared to long (>150 mm) femoropopliteal (FP) occlusive lesions. Methods Between 2006 and 2011, 254 patients (134 men; mean age 68 years) underwent FP angioplasty. The majority of patients (64%) were treated for critical limb ischemia. One hundred thirty-nine (55%) patients had short FP lesions ≤150 mm, while 115 patients had long FP lesions >150 mm. The mean lesion length was 78±43 mm in the short FP lesion group and 254±58 mm in the long FP lesion group. Duplex ultrasound follow-up with a peak systolic velocity ratio ≥2.0 was used to define restenosis. Results The overall procedure success rate was 98%. One hundred forty-eight (58%) patients underwent stent placement. The mean number of stents deployed for treatment of short FP lesions was 1.0±0.4 vs. 2.0±0.7 for long FP lesions (p<0.001). The primary patency rate of short FP lesions treated with balloon angioplasty vs. stenting was 66% vs. 63% at 1 year (p=0.7). For long FP lesions, the 1-year primary patency rates of balloon angioplasty vs. stenting were 34% vs. 49% (p=0.006). Balloon angioplasty of long FP lesions was also associated with significantly lower assisted primary and secondary patency compared to stenting (p<0.05 for all comparisons). Sustained clinical improvement was >90% at 30 days but declined to 62% to 75% at 1 year. Conclusion Balloon angioplasty and stent placement result in similar patency rates and clinical outcomes for shorter to medium-length FP lesions. In comparison, stent placement in long FP lesions is associated with superior outcomes to balloon angioplasty, even when multiple stents are required. Procedure success and clinical improvement can be achieved in the majority of patients, but rates of restenosis remain high.

Outcomes of covered versus bare-metal balloon-expandable stents for aortoiliac occlusive disease.

OBJECTIVE Randomized trials and retrospective data suggest that covered balloon-expandable (CBE) stents have better short-term patency compared with balloon-expandable bare-metal stents (BMSs) in the treatment of iliac artery disease. This study evaluated midterm outcomes of BMSs vs CBE stents placed in the common iliac artery (CIA) for aortoiliac occlusive disease. METHODS All endovascular interventions for symptomatic peripheral arterial occlusive disease performed at a single institution from 2006 to 2012 were reviewed. Patients undergoing stent placement in the CIA segment were included in the analysis. Demographic data, TransAtlantic Inter-Society Consensus (TASC) classification, stent type, patency, and limb reinterventions were compared. RESULTS For treatment of de novo distal aorta or CIA stenosis, 254 procedures were performed in 162 patients. BMSs were used in 190 arteries; CBE stents were used in 64 arteries. There was no difference in age, gender, or TASC classification between the two groups. Mean follow-up was 22 ± 16 months. Primary patency, assisted patency, and secondary patency were significantly better in the BMS group. CIAs treated with covered stents were more likely at 1 year or longer to require repeated intervention (hazard ratio, 2.5; 95% confidence interval, 1.2-5.3; P = .009). TASC classification did not predict need for reintervention in either group. Multivariate analysis revealed dual antiplatelet therapy to be the only other factor to affect patency during long-term follow-up. CONCLUSIONS In this study, BMSs had significantly better patency compared with CBE stents for treatment of aortoiliac occlusive disease. A randomized trial comparing patency as well as restenosis rates with long-term follow-up is needed to determine if there is any benefit from use of covered stents in the aortoiliac segment.

Peripheral artery disease in patients with diabetes: Epidemiology, mechanisms, and outcomes

Peripheral artery disease (PAD) is the atherosclerosis of lower extremity arteries and is also associated with atherothrombosis of other vascular beds, including the cardiovascular and cerebrovascular systems. The presence of diabetes mellitus greatly increases the risk of PAD, as well as accelerates its course, making these patients more susceptible to ischemic events and impaired functional status compared to patients without diabetes. To minimize these cardiovascular risks it is critical to understand the pathophysiology of atherosclerosis in diabetic patients. This, in turn, can offer insights into the therapeutic avenues available for these patients. This article provides an overview of the epidemiology of PAD in diabetic patients, followed by an analysis of the mechanisms by which altered metabolism in diabetes promotes atherosclerosis and plaque instability. Outcomes of PAD in diabetic patients are also discussed, with a focus on diabetic ulcers and critical limb ischemia.

Proximal versus distal embolic protection for carotid artery stenting: a national cardiovascular data registry analysis.

OBJECTIVES The aim of this study was to compare the stroke/death rates between proximal embolic protection devices (P-EPDs) and distal filter embolic protection devices (F-EPDs) in elective carotid artery stenting (CAS). BACKGROUND P-EPDs have theoretical advantages that may make them superior to F-EPDs for stroke prevention during CAS. METHODS We examined 10,246 consecutive elective CAS procedures performed with embolic protection in the NCDR CARE registry between January 2009 and March 2013. We analyzed crude and propensity-matched rates of in-hospital combined death/stroke in patients treated with P-EPDs versus F-EPDs. Secondary analyses included 30-day adverse event rates and stroke rates by the involved cerebrovascular territory. RESULTS P-EPDs were used in 590 of 10,246 cases (5.8%). Patients treated with P-EPDs had higher rates of symptomatic lesion status (46.8% vs. 39.7%, p<0.001), atrial fibrillation/flutter (16.1% vs. 13.0%, p=0.03), and history of a neurological event (51.2% vs. 46.6%, p=0.03). In unadjusted and propensity-matched analyses, differences in in-hospital stroke/death between P-EPD and F-EPD cohorts were nonsignificant (1.5% vs. 2.4%, p=0.16 and 1.6% vs. 2.0%, p=0.56, respectively). For patients with available data (n=7,693, 75.1%), 30-day adverse events rates were similar for P-EPDs and F-EPDs before (2.5% vs. 4.2%, p=0.07) and after (2.7% vs. 4.0%, p=0.22) propensity matching. CONCLUSIONS Use of a P-EPD during CAS was associated with low rates of in-hospital stroke/death similar to those with an F-EPD in the first comparative effectiveness study of the devices. An adequately powered randomized trial comparing clinical outcomes between these devices is unlikely to be feasible.