Phyo K. Myint

Association of Obstructive Sleep Apnea With Risk of Serious Cardiovascular Events A Systematic Review and Meta-Analysis

Background—The relationship between obstructive sleep apnea (OSA) and cardiovascular events remains unclear. We conducted a systematic review to determine the incident risk of cardiovascular events among patients with OSA. Methods and Results—We searched MEDLINE and EMBASE in January 2011 for prospective studies that followed up patients with OSA for incident ischemic heart disease, stroke, and cardiovascular mortality. Outcomes data were pooled using random effects meta-analysis and heterogeneity assessed with the I2 statistic. Regression analysis was performed to evaluate the effects of different gradations of OSA severity based on apnea-hypopnea index. We identified 9 relevant studies from 1731 citations. OSA was associated with incident stroke in a meta-analysis of 5 studies (8435 participants), odds ratio (OR) 2.24; 95% confidence interval (CI), 1.57–3.19; I2=7%. A significant association was seen in studies that were predominantly on men; OR, 2.87; 95% CI, 1.91–4.31, whereas data on women were sparse. In the overall analysis of 6 studies (8785 participants), OSA was nonsignificantly associated with ischemic heart disease (OR, 1.56; 95% CI, 0.83–2.91), with significant findings in the 5 studies that recruited mainly men (OR, 1.92; 95% CI, 1.06–3.48). Substantial heterogeneity was noted (I2=74%). OSA was linked to cardiovascular death in 2 studies involving 2446 participants (OR, 2.09; 95% CI, 1.20–3.65, I2=0%). Regression analysis showed greater likelihood of stroke or cardiovascular events with increasing apnea-hypopnea index values. Conclusions—OSA appears to be associated with stroke, but the relationship with ischemic heart disease and cardiovascular mortality needs further research.

Atrial fibrillation and incidence of dementia: A systematic review and meta-analysis

Background: Previous systematic reviews that examined whether atrial fibrillation (AF) is associated with dementia have relied on different study designs (including retrospective ones) and did not evaluate risk using meta-analysis. Methods: We searched Medline, Embase, and PsychINFO in September 2010 for published prospective studies reporting on the association between baseline AF and incident dementia. Pooled odds ratios for AF and dementia were calculated using the random effects model, with heterogeneity assessed using I2. Results: We identified 15 relevant studies covering 46,637 participants, mean age 71.7 years. One study that reported no significant difference in Mini-Mental State Examination scores between patients with or without AF could not be pooled. Meta-analysis of the remaining 14 studies showed that AF was associated with a significant increase in dementia overall (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.4 to 2.7, p < 0.0001), with substantial heterogeneity (I2 = 75%). When stratified by participants, the association was significant (with little heterogeneity) in studies focusing solely on patients with stroke (7 studies, OR 2.4, 95% CI 1.7 to 3.5, p < 0.001, I2 = 10%), and of borderline significance (with substantial heterogeneity) for studies in broader populations (7 studies, OR 1.6, 95% CI 1.0 to 2.7, p = 0.05, I2 = 87%). For conversion of mild cognitive impairment to dementia, one study showed a significant association with AF (OR 4.6, 95% CI 1.7 to 12.5). Conclusion: There is consistent evidence supporting an association between AF and increased incidence of dementia in patients with stroke whereas there remains considerable uncertainty about any link in the broader population. The potential association between AF and incident dementia in mild cognitive impairment merits further investigation.

Bariatric surgery and its impact on cardiovascular disease and mortality: a systematic review and meta-analysis.

BACKGROUND Bariatric surgery has been shown to improve cardiovascular risk factors but long term benefits for survival and cardiovascular events are still uncertain. METHODS We searched MEDLINE and EMBASE for parallel group studies that evaluated the clinical outcomes associated with bariatric surgery as compared to non-surgical treatment. Relevant studies were pooled using random effects meta-analysis for risk of myocardial infarction, stroke, cardiovascular events and mortality. RESULTS 14 studies met the inclusion criteria, which included 29,208 patients who underwent bariatric surgery and 166,200 nonsurgical controls (mean age 48 years, 30% male, follow up period ranged from 2 years to 14.7 years). Four studies were considered at moderate-high risk of bias, whilst ten studies were at moderate or lower risk of bias. Compared to nonsurgical controls there was more than 50% reduction in mortality amongst patients who had bariatric surgery (OR 0.48 95% CI 0.35-0.64, I2=86%, 14 studies). In pooled analysis of four studies with adjusted data, bariatric surgery was associated with a significantly reduced risk of composite cardiovascular adverse events (OR 0.54 95% CI 0.41-0.70, I2=58%). Bariatric surgery was also associated with significant reduction in specific endpoints of myocardial infarction (OR 0.46 95% CI 0.30-0.69, I2=79%, 4 studies) and stroke (OR 0.49 95% CI 0.32-0.75, I2=59%, 4 studies). CONCLUSIONS Data from observational studies indicates that patients undergoing bariatric surgery have a reduced risk of myocardial infarction, stroke, cardiovascular events and mortality compared to non-surgical controls. Future randomized studies should investigate whether these observations are reproduced in a clinical trials setting.

Value of severity scales in predicting mortality from community-acquired pneumonia: systematic review and meta-analysis

Background Several scoring systems have been used to predict mortality in patients with community-acquired pneumonia. The properties of commonly used risk stratification scales were systematically reviewed. Methods MEDLINE and EMBASE (January 1999–October 2009) were searched for prospective studies that reported mortality at 4–8 weeks in patients with radiographically-confirmed community-acquired pneumonia. The search focused on the Pneumonia Severity Index (PSI) and the three main iterations of the CURB (confusion, urea nitrogen, respiratory rate, blood pressure) scale (CURB-65, CURB, CRB-65), and test performance was evaluated based on ‘higher risk’ categories as follows: PSI class IV/V, CURB-65 (score ≥3), CURB (score ≥2) and CRB-65 (score ≥2). Random effects meta-analysis was used to generate summary statistics of test performance and receiver operating characteristic curves were used for predicting mortality. Results 402 articles were screened and 23 studies involving 22 753 participants (average mortality 7.4%) were retrieved. The respective diagnostic odds ratios for mortality were 10.77 (PSI), 6.40 (CURB-65), 5.97 (CRB-65) and 5.75 (CURB). Overall, PSI had the highest sensitivity and lowest specificity for mortality, CRB-65 was the most specific (but least sensitive) test and CURB-65/CURB were between the two. Negative predictive values for mortality were similar among the tests, ranging from 0.94 (CRB-65) to 0.98 (PSI), whereas positive predictive values ranged from 0.14 (PSI) to 0.28 (CRB-65). Conclusions The current risk stratification scales (PSI, CURB-65, CRB-65 and CURB) have different strengths and weaknesses. All four scales had good negative predictive values for mortality in populations with a low prevalence of death but were less useful with regard to positive predictive values.

Combined effect of health behaviours and risk of first ever stroke in 20,040 men and women over 11 years' follow-up in Norfolk cohort of European Prospective Investigation of Cancer (EPIC Norfolk): prospective population study.

Objective To quantify the potential combined impact of four health behaviours on incidence of stroke in men and women living in the general community. Design Population based prospective study (EPIC-Norfolk). Setting Norfolk, United Kingdom. Participants 20 040 men and women aged 40-79 with no known stroke or myocardial infarction at baseline survey in 1993-7, living in the general community, and followed up to 2007. Main outcome measure Participants scored one point for each health behaviour: current non-smoking, physically not inactive, moderate alcohol intake (1-14 units a week), and plasma concentration of vitamin C ≥50 µmol/l, indicating fruit and vegetable intake of at least five servings a day, for a total score ranging from 0 to 4. Results There were 599 incident strokes over 229 993 person years of follow-up; the average follow-up was 11.5 years. After adjustment for age, sex, body mass index (BMI), systolic blood pressure, cholesterol concentration, history of diabetes and aspirin use, and social class, compared with people with the four health behaviours the relative risks for stroke for men and women were 1.15 (95% confidence interval 0.89 to 1.49) for three health behaviours, 1.58 (1.22 to 2.05) for two, 2.18 (1.63 to 2.92) for one, and 2.31 (1.33 to 4.02) for none (P<0.001 for trend). The relations were consistent in subgroups stratified by sex, age, body mass index, and social class, and after exclusion of deaths within two years. Conclusion Four health behaviours combined predict more than a twofold difference in incidence of stroke in men and women.

Long-term Glycemic Variability and Risk of Adverse Outcomes: A Systematic Review and Meta-analysis

OBJECTIVE Glycemic variability is emerging as a measure of glycemic control, which may be a reliable predictor of complications. This systematic review and meta-analysis evaluates the association between HbA1c variability and micro- and macrovascular complications and mortality in type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS Medline and Embase were searched (2004–2015) for studies describing associations between HbA1c variability and adverse outcomes in patients with type 1 and type 2 diabetes. Data extraction was performed independently by two reviewers. Random-effects meta-analysis was performed with stratification according to the measure of HbA1c variability, method of analysis, and diabetes type. RESULTS Seven studies evaluated HbA1c variability among patients with type 1 diabetes and showed an association of HbA1c variability with renal disease (risk ratio 1.56 [95% CI 1.08–2.25], two studies), cardiovascular events (1.98 [1.39–2.82]), and retinopathy (2.11 [1.54–2.89]). Thirteen studies evaluated HbA1c variability among patients with type 2 diabetes. Higher HbA1c variability was associated with higher risk of renal disease (1.34 [1.15–1.57], two studies), macrovascular events (1.21 [1.06–1.38]), ulceration/gangrene (1.50 [1.06–2.12]), cardiovascular disease (1.27 [1.15–1.40]), and mortality (1.34 [1.18–1.53]). Most studies were retrospective with lack of adjustment for potential confounders, and inconsistency existed in the definition of HbA1c variability. CONCLUSIONS HbA1c variability was positively associated with micro- and macrovascular complications and mortality independently of the HbA1c level and might play a future role in clinical risk assessment.

Pre-operative indicators for mortality following hip fracture surgery: a systematic review and meta-analysis

OBJECTIVE hip fracture is a common and serious condition associated with high mortality. This study aimed to identify pre-operative characteristics which are associated with an increased risk of mortality after hip fracture surgery. DESIGN systematic search of published and unpublished literature databases, including EMBASE, MEDLINE, AMED, CINAHL, PubMed and the Cochrane Library, was undertaken to identify all clinical studies on pre-operative predictors of mortality after surgery in hip fracture with at least 3-month follow-up. Data pertaining to the study objectives was extracted by two reviewers independently. Where study homogeneity was evidence, a meta-analysis of pooled relative risk and 95% confidence intervals was performed for mortality against pre-admission characteristics. RESULTS fifty-three studies including 544,733 participants were included. Thirteen characteristics were identified as possible pre-operative indicators for mortality. Following meta-analysis, the four key characteristics associated with the risk of mortality up to 12 months were abnormal ECG (RR: 2.00; 95% CI: 1.45, 2.76), cognitive impairment (RR: 1.91; 95% CI: 1.35, 2.70), age >85 years (RR: 0.42; 95% CI: 0.20, 0.90) and pre-fracture mobility (RR: 0.13; 95% CI: 0.05, 0.34). Other statistically significant pre-fracture predictors of increased mortality were male gender, being resident in a care institution, intra-capsular fracture type, high ASA grade and high Charlson comorbidity score on admission. CONCLUSIONS this review has identified the characteristics of patients with a high risk of mortality after a hip fracture surgery beyond the peri-operative period who may benefit from comprehensive assessment and appropriate management. PROSPERO REGISTRATION NUMBER CRD42012002107.

Effect of Dysphasia and Dysphagia on Inpatient Mortality and Hospital Length of Stay: A Database Study

OBJECTIVES: To examine the effect of dysphasia and dysphagia on stroke outcome.

Effect of medications with anti-cholinergic properties on cognitive function, delirium, physical function and mortality: a systematic review

OBJECTIVES to determine the effect of drugs with anti-cholinergic properties on relevant health outcomes. DESIGN electronic published and unpublished literature/trial registries were systematically reviewed. Studies evaluating medications with anti-cholinergic activity on cognitive function, delirium, physical function or mortality were eligible. RESULTS forty-six studies including 60,944 participants were included. Seventy-seven percent of included studies evaluating cognitive function (n = 33) reported a significant decline in cognitive ability with increasing anti-cholinergic load (P < 0.05). Four of five included studies reported no association with delirium and increasing anti-cholinergic drug load (P > 0.05). Five of the eight included studies reported a decline in physical function in users of anti-cholinergics (P < 0.05). Three of nine studies evaluating mortality reported that the use of drugs with anti-cholinergic properties was associated with a trend towards increased mortality, but this was not statistically significant. The methodological quality of the evidence-base ranged from poor to very good. CONCLUSION medicines with anti-cholinergic properties have a significant adverse effect on cognitive and physical function, but limited evidence exists for delirium or mortality outcomes.

The association between older age and receipt of care and outcomes in patients with acute coronary syndromes: a cohort study of the Myocardial Ischaemia National Audit Project (MINAP)

AIMS Older people increasingly constitute a large proportion of the acute coronary syndrome (ACS) population. We examined the relationship of age with receipt of more intensive management and secondary prevention medicine. Then, the comparative association of intensive management (reperfusion/angiography) over a conservative strategy on time to death was investigated by age. METHODS AND RESULTS Using data from 155 818 patients in the national registry for ACS in England and Wales [the Myocardial Ischaemia National Audit Project (MINAP)], we found that older patients were incrementally less likely to receive secondary prevention medicines and intensive management for both ST-elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI). In STEMI patients ≥85 years, 55% received reperfusion compared with 84% in those aged 18 to <65 [odds ratio 0.22 (95% CI 0.21, 0.24)]. Not receiving intensive management was associated with worse survival [mean follow-up 2.29 years (SD 1.42)] in all age groups (adjusted for sex, cardiovascular risk factors, co-morbidities, healthcare factors, and case severity), but there was an incremental reduction in survival benefit from intensive management with increasing age. In STEMI patients aged 18-64, 65-74, 75-84, and ≥85, adjusted hazard ratios (HRs) for all-cause mortality comparing conservative treatment to intensive management were 1.98 (1.78, 2.19), 1.65 (1.51, 1.80), 1.62 (1.52, 1.72), and 1.36 (1.27, 1.47), respectively. In NSTEMI patients, the respective HRs were 4.37 (4.00, 4.78), 3.76 (3.54, 3.99), 2.79 (2.67, 2.91), and 1.90 (1.77, 2.04). CONCLUSION We found an incremental reduction in the use of evidence-based therapies with increasing age using a national ACS registry cohort. While survival benefit from more intensive management reduced with older age, better survival was associated with intensive management at all ages highlighting the requirement to improve standard of care in older patients with ACS.