METHODS: We surveyed HFrEF patients from two hospitals in Malaysia, using Malay, English or Chinese versions of EQ-5D-5L. EQ-5D-5L dimensional scores were converted to utility scores using the Malaysian value set. A confirmatory factor analysis longitudinal model was constructed. The utility and visual analog scale (VAS) scores were evaluated for validity (convergent, known-group, responsiveness), and measurement equivalence of the three language versions.
RESULTS: 200 HFrEF patients (mean age = 61 years), predominantly male (74%) of Malay ethnicity (55%), completed the admission and discharge EQ-5D-5L questionnaire in Malay (49%), English (26%) or Chinese (25%) languages. 173 patients (86.5%) were followed up at 1-month post-discharge (1MPD). The standardized factor loadings and average variance extracted were ≥ 0.5 while composite reliability was ≥ 0.7, suggesting convergent validity. Patients with older age and higher New York Heart Association (NYHA) class reported significantly lower utility and VAS scores. The change in utility and VAS scores between admission and discharge was large, while the change between discharge and 1MPD was minimal. The minimal clinically important difference for utility and VAS scores was ±0.19 and ±11.01, respectively. Malay and English questionnaire were equivalent while the equivalence of Malay and Chinese questionnaire was inconclusive.
LIMITATION: This study only sampled HFrEF patients from two teaching hospitals, thus limiting the generalizability of results to the entire heart failure population.
CONCLUSION: EQ-5D-5L is a valid questionnaire to measure health-related quality of life and estimate utility values among HFrEF patients in Malaysia. The Malay and English versions of EQ-5D-5L appear equivalent for clinical and economic assessments.
METHODS: A cross-sectional study was conducted on T2DM patients at a tertiary hospital outpatient using the Malay and English version of the EQ-5D-5L questionnaire. Health utility values were derived using the Malaysian EQ-5D-5L value set. Ordinary least squares (OLS) multivariable regression model was used to estimate the health utility decrements associated with T2DM-related complications and clinical characteristics.
RESULTS: A total of 513 T2DM patients were recruited. Overall, pain was the most affected of all five EQ-5D-5L dimensions. Patients with foot ulcer, amputation, severe heart failure and frequent hypoglycemia reported more problems collectively in all EQ-5D-5L dimensions. Older age, lower education level, longer duration of T2DM, urine protein creatine index (UPCI) > 0.02 g/mmol, and injection therapy were significantly associated with lower EQ-5D-5L utility values (p heart failure 0.65 (interquartile range, IQR 0.50), frequent hypoglycemia 0.74 (0.22) and being amputated 0.78 (0.47). In the multivariable regression model after controlling for sociodemographic and clinical characteristics, the largest utility value decrement was observed for amputation (- 0.158, SE 0.087, p = 0.05), frequent hypoglycemia (- 0.101, SE 0.030, p = 0.001), myocardial infarction (-0.050, SE 0.022, p = 0.022) and obesity (-0.034, SE 0.016, p = 0.029).
CONCLUSION: Larger utility value decrements were found for severe stages of complications. These findings suggest the value of defining severity of complications in utility elicitation studies. The utility decrement quantified for different T2DM complication severity will be useful for economic evaluations within diabetic-related fields.
METHODS AND RESULTS: Individual patient data for 16 922 patients from five randomized clinical trials and 46 914 patients from two HF registries were included. The registry patients were categorized into trial-eligible and non-eligible groups using the most commonly used inclusion and exclusion criteria. A total of 26 104 (56%) registry patients fulfilled the eligibility criteria. Unadjusted all-cause mortality rates at 1 year were lowest in the trial population (7%), followed by trial-eligible patients (12%) and trial-non-eligible registry patients (26%). After adjustment for age and sex, all-cause mortality rates were similar between trial participants and trial-eligible registry patients [standardized mortality ratio (SMR) 0.97; 95% confidence interval (CI) 0.92-1.03] but cardiovascular mortality was higher in trial participants (SMR 1.19; 1.12-1.27). After full case-mix adjustment, the SMR for cardiovascular mortality remained higher in the trials at 1.28 (1.20-1.37) compared to RCT-eligible registry patients.
CONCLUSION: In contemporary HF registries, over half of HFrEF patients would have been eligible for trial enrolment. Crude clinical event rates were lower in the trials, but, after adjustment for case-mix, trial participants had similar rates of survival as registries. Despite this, they had about 30% higher cardiovascular mortality rates. Age and sex were the main drivers of differences in clinical outcomes between HF trials and observational HF registries.
OBJECTIVE: To investigate the association of sitting time with mortality and major CVD in countries at different economic levels using data from the Prospective Urban Rural Epidemiology study.
DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study included participants aged 35 to 70 years recruited from January 1, 2003, and followed up until August 31, 2021, in 21 high-income, middle-income, and low-income countries with a median follow-up of 11.1 years.
EXPOSURES: Daily sitting time measured using the International Physical Activity Questionnaire.
MAIN OUTCOMES AND MEASURES: The composite of all-cause mortality and major CVD (defined as cardiovascular death, myocardial infarction, stroke, or heart failure).
RESULTS: Of 105 677 participants, 61 925 (58.6%) were women, and the mean (SD) age was 50.4 (9.6) years. During a median follow-up of 11.1 (IQR, 8.6-12.2) years, 6233 deaths and 5696 major cardiovascular events (2349 myocardial infarctions, 2966 strokes, 671 heart failure, and 1792 cardiovascular deaths) were documented. Compared with the reference group (<4 hours per day of sitting), higher sitting time (≥8 hours per day) was associated with an increased risk of the composite outcome (hazard ratio [HR], 1.19; 95% CI, 1.11-1.28; Pfor trend < .001), all-cause mortality (HR, 1.20; 95% CI, 1.10-1.31; Pfor trend < .001), and major CVD (HR, 1.21; 95% CI, 1.10-1.34; Pfor trend < .001). When stratified by country income levels, the association of sitting time with the composite outcome was stronger in low-income and lower-middle-income countries (≥8 hours per day: HR, 1.29; 95% CI, 1.16-1.44) compared with high-income and upper-middle-income countries (HR, 1.08; 95% CI, 0.98-1.19; P for interaction = .02). Compared with those who reported sitting time less than 4 hours per day and high physical activity level, participants who sat for 8 or more hours per day experienced a 17% to 50% higher associated risk of the composite outcome across physical activity levels; and the risk was attenuated along with increased physical activity levels.
CONCLUSIONS AND RELEVANCE: High amounts of sitting time were associated with increased risk of all-cause mortality and CVD in economically diverse settings, especially in low-income and lower-middle-income countries. Reducing sedentary time along with increasing physical activity might be an important strategy for easing the global burden of premature deaths and CVD.
METHODS: Health-related quality of life was captured using the EuroQol-5 Dimension-3 Level (EQ-5D-3L), with data collected at baseline and throughout the trial. Multilevel mixed-effects linear regression with random effects estimated health-related quality of life over time, capturing variation between hospital sites and individuals, and a fixed-effects linear model estimated the impact of cardiovascular and gastrointestinal events.
RESULTS: Patients were followed for a median of 5 years (interquartile range 3.4-6.0). The average baseline EQ-5D score of 0.930 (SD 0.104) remained relatively unchanged over the trial period with no evidence of statistically significant differences in EQ-5D score between randomized treatment groups. The largest decrement in the year of an event was estimated for stroke (-0.107, P heart failure (-0.039, P = .022), MI (-0.021, P = .047), angina (-0.012, P = .047), and gastrointestinal events (-0.005, P = .430). MI and stroke reduced health-related quality of life beyond the year in which the event occurred (-0.031, P = .006, and -0.067, P heart failure, and angina reduce health-related quality of life around the time they occurred, but only MI and stroke impacted on longer-term health-related quality of life.
METHODS: We did a systematic review and meta-analysis of randomised controlled trials including IPD. We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Epub Ahead of Print, Embase, Science Citation Index, the Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, and Database of Abstracts of Review of Effects for literature from 1992 onwards (date of search, Aug 27, 2018). The following inclusion criteria were applied: (1) men aged 18 years and older with a screening testosterone concentration of 12 nmol/L (350 ng/dL) or less; (2) the intervention of interest was treatment with any testosterone formulation, dose frequency, and route of administration, for a minimum duration of 3 months; (3) a comparator of placebo treatment; and (4) studies assessing the pre-specified primary or secondary outcomes of interest. Details of study design, interventions, participants, and outcome measures were extracted from published articles and anonymised IPD was requested from investigators of all identified trials. Primary outcomes were mortality, cardiovascular, and cerebrovascular events at any time during follow-up. The risk of bias was assessed using the Cochrane Risk of Bias tool. We did a one-stage meta-analysis using IPD, and a two-stage meta-analysis integrating IPD with data from studies not providing IPD. The study is registered with PROSPERO, CRD42018111005.
FINDINGS: 9871 citations were identified through database searches and after exclusion of duplicates and of irrelevant citations, 225 study reports were retrieved for full-text screening. 116 studies were subsequently excluded for not meeting the inclusion criteria in terms of study design and characteristics of intervention, and 35 primary studies (5601 participants, mean age 65 years, [SD 11]) reported in 109 peer-reviewed publications were deemed suitable for inclusion. Of these, 17 studies (49%) provided IPD (3431 participants, mean duration 9·5 months) from nine different countries while 18 did not provide IPD data. Risk of bias was judged to be low in most IPD studies (71%). Fewer deaths occurred with testosterone treatment (six [0·4%] of 1621) than placebo (12 [0·8%] of 1537) without significant differences between groups (odds ratio [OR] 0·46 [95% CI 0·17-1·24]; p=0·13). Cardiovascular risk was similar during testosterone treatment (120 [7·5%] of 1601 events) and placebo treatment (110 [7·2%] of 1519 events; OR 1·07 [95% CI 0·81-1·42]; p=0·62). Frequently occurring cardiovascular events included arrhythmia (52 of 166 vs 47 of 176), coronary heart disease (33 of 166 vs 33 of 176), heart failure (22 of 166 vs 28 of 176), and myocardial infarction (10 of 166 vs 16 of 176). Overall, patient age (interaction 0·97 [99% CI 0·92-1·03]; p=0·17), baseline testosterone (interaction 0·97 [0·82-1·15]; p=0·69), smoking status (interaction 1·68 [0·41-6·88]; p=0.35), or diabetes status (interaction 2·08 [0·89-4·82; p=0·025) were not associated with cardiovascular risk.
INTERPRETATION: We found no evidence that testosterone increased short-term to medium-term cardiovascular risks in men with hypogonadism, but there is a paucity of data evaluating its long-term safety. Long-term data are needed to fully evaluate the safety of testosterone.
FUNDING: National Institute for Health Research Health Technology Assessment Programme.
METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols statement was used as a template for this protocol. A systematic search of Medline, Embase and Global Health from database inception to present will be conducted to identify prospective studies reporting on the associations between major measures of body composition (body mass index, waist circumference, waist-hip ratio, total body fat, visceral adiposity tissue and lean mass) and risk of heart failure. Article screening and selection will be performed by two reviewers independently, and disagreements will be adjudicated by consensus or by a third reviewer. Data from eligible articles will be extracted, and article quality will be assessed using the Newcastle-Ottawa Scale. Relative risks (and 95% CIs) will be pooled in a fixed effect meta-analysis, if there is no prohibitive heterogeneity of studies as assessed using the Cochrane Q statistic and I2 statistic. Subgroup analyses will be by age, sex, ethnicity and heart failure subtypes. Publication bias in the meta-analysis will be assessed using Egger's test and funnel plots.
ETHICS AND DISSEMINATION: This work is secondary analyses on published data and ethical approval is not required. We plan to publish results in an open-access peer-reviewed journal, present it at international and national conferences, and share the findings on social media.
PROSPERO REGISTRATION NUMBER: CRD42020224584.
AIM: The aim of the study was to determine the influence of various risk factors on ST2 levels in patients with HFpEF and diabetes mellitus type 2 (T2DM).
MATERIALS AND METHODS: A total of one hundred and thirty-four patients (74 females and 60 males, 51 diabetic patients and 83 patients without T2DM with HFpEF were examined. Duration of HF and T2DM, common risk factors, such as smoking, overweight, clinical examination, parameters of carbohydrate and lipid metabolism, glomerular filtration rate (GFR) and M235T polymorphism of ATG have been used. Multivariate backward stepwise cox regression analysis was performed in Statistica 10,0. p<0,05 was considered statistically significant.
RESULTS: ST2 level in patients with HFpEF associated with T2DM exceeded this value in patients with HFpEF without T2DM and was 23.26 ng/ml (18.5: 29.3) vs. 20.39 ng/ml (18.3: 24.6), respectively (p<0,05). To assess the cumulative effect of the studied factors on the ST2 level, we performed the Cox's stepwise multivariate regression analysis. Smoking, HOMA-IR (Homeostatic Model Assessment for Insulin Resistance), glucose, HbA1 and insulin levels were found to be the most significant factors influencing ST2 levels in patients with HF and T2DM, indicating a significant effect of DM type 2 on ST2 concentration.
CONCLUSIONS: Smoking, HOMA-IR, glucose, HbA1, and insulin levels can significantly affect ST2 levels in patients with T2DM and HFpEF.
METHODS: Data from the Coronary Artery Risk Development in Young Adults study were analyzed. Participants (n = 2,833) had a mean baseline age of 30.1 years; 45% were black, and 56% were women. Generalized estimating equation logistic regression was used to estimate age-related probabilities of stage B LV abnormalities (remodeling, hypertrophy, or dysfunction) and logistic regression to examine risk factor-adjusted associations between baseline LV parameters and incident abnormalities. Cox regression was used to assess whether baseline LV parameters associated with incident stage B LV abnormalities were also associated with incident clinical (stage C/D) HF events over >25 years' follow-up.
RESULTS: Probabilities of stage B LV abnormalities at ages 25 and 60 years were 10.5% (95% CI, 9.4%-11.8%) and 45.0% (95% CI, 42.0%-48.1%), with significant race-sex disparities (e.g., at age 60, black men 52.7% [95% CI, 44.9%-60.3%], black women 59.4% [95% CI, 53.6%-65.0%], white men 39.1% [95% CI, 33.4%-45.0%], and white women 39.1% [95% CI, 33.9%-44.6%]). Over 25 years, baseline LV end-systolic dimension indexed to height was associated with incident systolic dysfunction (adjusted odds ratio per 1 SD higher, 2.56; 95% CI, 1.87-3.52), eccentric hypertrophy (1.34; 95% CI, 1.02-1.75), concentric hypertrophy (0.69; 95% CI, 0.51-0.91), and concentric remodeling (0.68; 95% CI, 0.58-0.79); baseline LV mass indexed to height2.7 was associated with incident eccentric hypertrophy (1.70; 95% CI, 1.25-2.32]), concentric hypertrophy (1.63; 95% CI, 1.19-2.24), and diastolic dysfunction (1.24; 95% CI, 1.01-1.52). Among the entire cohort with baseline echocardiographic data available (n = 4,097; 72 HF events), LV end-systolic dimension indexed to height and LV mass indexed to height2.7 were significantly associated with incident clinical HF (adjusted hazard ratios per 1 SD higher, 1.56 [95% CI, 1.26-1.93] and 1.42 [95% CI, 1.14-1.75], respectively).
CONCLUSIONS: Stage B LV abnormalities and related racial disparities were present in young adulthood, increased with age, and were associated with baseline variation in indexed LV end-systolic dimension and mass. Baseline indexed LV end-systolic dimension and mass were also associated with incident clinical HF. Efforts to prevent the LV abnormalities underlying clinical HF should start from a young age.
DESIGN: Observational study.
SETTING: A single-centre study in which eligible patients were recruited from T2DM clinic. Following consent, patients completed a questionnaire and underwent physical examinations. Patients had blood drawn for laboratory investigations and had a transthoracic echocardiography.
PARTICIPANTS: A total of 305 patients who were not known to have CVD were recruited. Patients with deranged liver function tests and end stage renal failure were excluded.
MAIN OUTCOME MEASURES: Echocardiographic parameters such as left ventricular ejection fraction, left ventricular mass index (LVMI), left ventricular hypertrophy, left atrial enlargement and diastolic function were examined.
RESULTS: A total of 305 patients predominantly females (65%), with mean body mass index of 27.5 kg/m2 participated in this study. None of them had either a history or signs and symptoms of CVD. Seventy-seven percent of patients had a history of hypertension and 83% of this study population had T2DM for more than 10 years. Mean HbA1c of 8.3% was recorded. Almost all patients were taking metformin. Approximately, 40% of patients were on newer anti-T2DM agents such as sodium-glucose cotransporter-2 and dipeptidyl peptidase 4 inhibitors. Fifty-seven percent (n=174) of the study population had SBHF at the time of study: diastolic dysfunction, increased LVMI and increased left atrial volume index (LAVI) were noted in 51 patients (17%), 128 patients (42%) and 98 patients (32%), respectively. Thirty-seven patients (12%) had both increase LVMI and LAVI.
CONCLUSION: Our study has revealed a high prevalence of SBHF in T2DM patients without overt cardiac disease in Malaysia that has one of the highest prevalence of TDM in the world.
METHODS: A substudy of a prospective interrupted time series cohort study conducted at three time points in EDs in Australia, New Zealand, Singapore, Hong Kong and Malaysia of patients presenting to the ED with dyspnoea as a main symptom. Data were collected over three 72-h periods and included demographics, co-morbidities, mode of arrival, usual medications, ED investigations and treatment, ED diagnosis and disposition, and outcome. The primary outcomes of interest are the epidemiology and outcome of patients aged 75 years or older presenting to the ED with dyspnoea.
RESULTS: 1097 patients were included. Older patients with dyspnoea made up 1.8% [95% confidence interval (CI) 1.7-1.9%] of ED presentations. The most common diagnoses were heart failure (25.3%), lower respiratory tract infection (25.2%) and chronic obstructive pulmonary disease (17.6%). Hospital ward admission was required for 82.6% (95% CI 80.2-84.7%), with 2.5% (95% CI 1.7-3.6%) requiring intensive care unit (ICU) admission. In-hospital mortality was 7.9% (95% CI 6.3-9.7%). Median length of stay was 5 days (interquartile range 2-8 days).
CONCLUSION: Older patients with dyspnoea make up a significant proportion of ED case load, and have a high admission rate and significant mortality. Exacerbations or worsening of pre-existing chronic disease account for a large proportion of cases which may be amenable to improved chronic disease management.