Low bone mineral density and coronary artery disease: A systematic review and meta-analysis.

Coronary artery disease (CAD) and osteoporosis both cause significant morbidity and mortality. Recent interest in inflammation and the bone-vascular axis suggests a mechanistic link between the two conditions. This review and meta-analysis was conducted to examine the potential association between low bone mineral density (BMD) and CAD in adults. Two authors searched for studies that examined the association between low BMD and CAD. Risk of bias assessment was conducted using the modified Newcastle Ottawa score. Ten studies were selected from the 2258 unique records identified. Pooled analysis showed a significant association between low BMD and CAD (OR 1.65, 95%CI 1.37-2.39, p < 0.01). Subgroup analysis investigating males and females separately was not significant. The subgroup analyses looking for any differences across geographic locations and differences between coronary imaging modalities were also negative. Studies with adjusted ORs (n = 4) were also pooled (OR 3.01, 95%CI 0.91-9.99, p = 0.07). Low BMD is associated with CAD; however, it is unclear whether this result is confounded by common risk factors given the heterogeneity between study populations and methodologies. Further large-scale epidemiological studies are required.

Atherothrombosis in Acute Coronary Syndromes-From Mechanistic Insights to Targeted Therapies.

The atherothrombotic substrates for acute coronary syndromes (ACS) consist of plaque ruptures, erosions and calcified nodules, while the non-atherothrombotic etiologies, such as spontaneous coronary artery dissection, coronary artery spasm and coronary embolism are the rarer causes of ACS. The purpose of this comprehensive review is to (1) summarize the histopathologic insights into the atherothrombotic plaque subtypes in acute ACS from postmortem studies; (2) provide a brief overview of atherogenesis, while mainly focusing on the events that lead to plaque destabilization and disruption; (3) summarize mechanistic data from clinical studies that have used intravascular imaging, including high-resolution optical coherence tomography, to assess culprit plaque morphology and its underlying pathobiology, especially the newly described role of innate and adaptive immunity in ACS secondary to plaque erosion; (4) discuss the utility of intravascular imaging for effective treatment of patients presenting with ACS by percutaneous coronary intervention; and (5) discuss the opportunities that these mechanistic and imaging insights may provide for more individualized treatment of patients with ACS.

Colchicine Inhibits Neutrophil Extracellular Trap Formation in Patients With Acute Coronary Syndrome After Percutaneous Coronary Intervention.

Background Release of neutrophil extracellular traps (NETs) after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) is associated with periprocedural myocardial infarction, as a result of microvascular obstruction via pro-inflammatory and prothrombotic pathways. Colchicine is a well-established anti-inflammatory agent with growing evidence to support use in patients with coronary disease. However, its effects on post-PCI NET formation in ACS have not been explored. Methods and Results Sixty patients (40 ACS; 20 stable angina pectoris) were prospectively recruited and allocated to colchicine or no treatment. Within 24 hours of treatment, serial coronary sinus blood samples were collected during PCI. Isolated neutrophils from 10 patients with ACS post-PCI and 4 healthy controls were treated in vitro with colchicine (25 nmol/L) and stimulated with either ionomycin (5 µmol/L) or phorbol 12-myristate 13-acetate (50 nmol/L). Extracellular DNA was quantified using Sytox Green and fixed cells were stained with Hoechst 3342 and anti-alpha tubulin. Baseline characteristics were similar across both treatment and control arms. Patients with ACS had higher NET release versus patients with stable angina pectoris (P<0.001), which was reduced with colchicine treatment (area under the curve: 0.58 versus 4.29; P<0.001). In vitro, colchicine suppressed unstimulated (P<0.001), phorbol 12-myristate 13-acetate-induced (P=0.009) and ionomycin-induced (P=0.002) NET formation in neutrophils isolated from patients with ACS post-PCI, but not healthy controls. Tubulin organization was impaired in neutrophils from patients with ACS but was restored by colchicine treatment. Conclusions Colchicine suppresses NET formation in patients with ACS post-PCI by restoring cytoskeletal dynamics. These findings warrant further investigation in randomized trials powered for clinical end points. Registration URL: https://anzctr.org.au; Unique identifier: ACTRN12619001231134.

Colchicine for Stroke Prevention: A Systematic Review and Meta-analysis.

PURPOSE: There has been recent interest in the role of colchicine in cardiovascular diseases, given the implication of inflammation in the pathogenesis of atherothrombosis. This systematic review assessed the role of colchicine in preventing primary or secondary stroke/transient ischemic attack (TIA) in an adult population. METHODS: Four databases were electronically searched: MEDLINE, EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), and OpenGrey. Studies were eligible if they reported stroke or TIA incidence as a primary/secondary end point, or as an adverse event. Only case-control studies, cohort studies, and randomized controlled trials (RCTs) were eligible. The primary end point was a pooled estimate using relative risk ratios (RRs) with 95% CIs. Two-sided P values were considered significant if P < 0.05. Statistical heterogeneity was assessed by using the Cochrane Q statistic and the Higgin's I2 statistic. An a priori decision was made to conduct a subgroup analysis based on study type. FINDINGS: A total of 5 studies were eligible for inclusion: 4 RCTs and 1 cohort study. There were 77 reported stroke/TIA events of a combined 2170 patients. Pooling all studies, stroke incidence was lower in the colchicine versus non-colchicine users (RR, 0.37; 95% CI, 0.22-0.62; P = 0.0002). There was no statistical heterogeneity (χ2 = 2.72; df = 4; P = 0.61; I2 = 0%). Pooling 4 RCTs as determined a priori, there was no significant effect of colchicine on stroke incidence (RR, 0.61; 95% CI, 0.17-2.17; P = 0.57). Results of the single cohort study suggested that colchicine reduced stroke incidence (RR, 0.33; 95% CI, 0.19-0.59; P = 0.0002). IMPLICATIONS: Colchicine has a potential protective benefit in both primary and secondary stroke/TIA incidence. Current data are inconclusive, likely due to the small sample sizes of available RCTs. Large-scale pragmatic RCTs are required to provide robust evidence in this domain.

Current management aspects in adult congenital heart disease: non-surgical closure of patent foramen ovale.

A patent foramen ovale (PFO) is a remnant interatrial communication, best diagnosed with transoesophageal echocardiography (TOE) and bubble study. Although quite common and often asymptomatic, PFO is associated with cryptogenic stroke and migraine. Approximately one-half of patients with a cryptogenic stroke have a PFO, and the dilemma regarding whether or not to proceed with percutaneous device closure, to reduce the risk of future recurrent events due to paradoxical embolism, has been subject to debate for nearly two decades. Despite promising observational data, initial randomised clinical trials failed to demonstrate superiority of closure over medical therapy. However, long-term follow-up data from one of these early trials, combined with two new randomised trials, have provided more evidence for the benefits of closure in selected patients. This new evidence suggests that younger patients with high-risk features such as an atrial septal aneurysm (ASA) or large interatrial shunt are more likely to benefit from PFO closure, after fastidious exclusion of an alternative cause for the index stroke. However, issues which require further clarification include whether anticoagulant therapy is preferable to antiplatelet therapy for medical management, and which particular type of closure device is optimal. Finally, despite promising retrospective observational data suggesting improvement in migraine attacks after PFO closure, high quality evidence is lacking in this regard.

Epidemiology of Peripheral Lymph Node Tuberculosis and Genotyping of M. tuberculosis Strains: A Case-Control Study.

BACKGROUND: This study examined potential risk factors of lymph node tuberculosis (LNTB), including phylogenetic lineages of Mycobacterium tuberculosis (MTB), in comparison to pulmonary tuberculosis (PTB) in a setting with an ethnically diverse population. METHODS: We conducted a case-control study at a major tuberculosis clinic in Sydney, Australia, which included all patients with peripheral LNTB seen at the clinic between 2000 and 2012. Controls were randomly selected patients with PTB seen at the same clinic during the study period. Epidemiological data were extracted from the hospital electronic database and medical records. Associations between LNTB and age, sex, ethnicity, comorbidities and phylogenetic lineages of MTB in comparison to PTB were examined using logistic regression in univariate and multivariate analyses. RESULTS: There were 212 cases with LNTB and 424 randomly selected controls with PTB. Among patients with LNTB, 74% were female and the mean age (standard deviation, SD) was 42 (16) years. Among patients with PTB, 43% were female and the mean age was 44 (22) years. Females, 45 to 64-year-olds and Southern Asians had an increased risk for LNTB (OR 3.13, 95% CI 2.10-4.67; OR 2.50, 95% CI 1.29-4.84; OR 3.95, 95% CI 1.54-10.12 respectively). Patients with diabetes were at a higher risk of PTB (OR 0.40, 95% CI 0.19 - 0.83 for LNTB). A subset analysis showed that patients infected with the East African Indian strain of MTB were more likely to develop LNTB (OR 10.07, 95% CI 2.37-42.77). CONCLUSIONS: An increased risk for LNTB (but still lower rates than for PTB) was found among females, people aged 45 to 64 years and people born in Southern Asia. An increased risk for PTB was found among patients with diabetes. The East African Indian strain of MTB was significantly associated with a higher likelihood of LNTB compared to other MTB strains.