Risk of cardiovascular disease morbidity and mortality in frail and pre-frail older adults: Results from a meta-analysis and exploratory meta-regression analysis.
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SUBMITTER: Veronese N
PROVIDER: S-EPMC6047747 | biostudies-literature | 2017 May
REPOSITORIES: biostudies-literature
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Risk of cardiovascular disease morbidity and mortality in frail and pre-frail older adults: Results from a meta-analysis and exploratory meta-regression analysis.
Veronese Nicola N Cereda Emanuele E Stubbs Brendon B Solmi Marco M Luchini Claudio C Manzato Enzo E Sergi Giuseppe G Manu Peter P Harris Tamara T Fontana Luigi L Strandberg Timo T Amieva Helene H Dumurgier Julien J Elbaz Alexis A Tzourio Christophe C Eicholzer Monika M Rohrmann Sabine S Moretti Claudio C D'Ascenzo Fabrizio F Quadri Giorgio G Polidoro Alessandro A Lourenço Roberto Alves RA Moreira Virgilio Garcia VG Sanchis Juan J Scotti Valeria V Maggi Stefania S Correll Christoph U CU
Ageing research reviews 20170128
Frailty is common and associated with poorer outcomes in the elderly, but its role as potential cardiovascular disease (CVD) risk factor requires clarification. We thus aimed to meta-analytically evaluate the evidence of frailty and pre-frailty as risk factors for CVD. Two reviewers selected all studies comparing data about CVD prevalence or incidence rates between frail/pre-frail vs. robust. The association between frailty status and CVD in cross-sectional studies was explored by calculating an ...[more]
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Project description:BackgroundFrailty is characterized by a progressive decline in the physiological functions of multiple body systems that lead to a more vulnerable condition, which is prone to the development of various adverse events, such as falls, hospitalization, and mortality. This study aims to determine whether frailty increases mortality compared to pre-frailty and to identify variables associated with a higher risk of mortality.MaterialsTwo cohorts, frail and pre-frail subjects, are evaluated according to the Fried phenotype. A complete examination of frailty, cognitive status, comorbidities and pharmacology was carried out at hospital admission and was extracted through electronic health record (EHR). Mortality was evaluated from the EHR.MethodsKaplan-Meier estimates of survival probability functions were calculated at two years censoring time for frail and pre-frail cohorts. The log-rank test assessed significant differences between survival probability functions. Significant variables for frailty (p < 0-05) were extracted by independent sample t-test. Further selection was based on variable significance found in multivariate logistic regression discrimination between frail and pre-frail subjects. Cox regression over univariate t-test-selected variables was calculated to identify variables associated with higher proportional hazard risks (HR) at two years.ResultsFrailty is associated with greater mortality at two years censoring time than pre-frailty (log-rank test, p < 0.0001). Variables with significant (p < 0.05) association with mortality identified in both cohorts (HR 95% (CI in the frail cohort) are male sex (0.44 (0.29-0.66)), age (1.05 (1.01-1.09)), weight (0.98 (0.96-1.00)), and use of proton-pump inhibitors (PPIs) (0.60 (0.41-0.87)). Specific high-risk factors in the frail cohort are readmission at 30 days (0.50 (0.33-0.74)), SPPB sit and stand (0.62 (0.45-0.85)), heart failure (0.67 (0.46-0.98)), use of antiplatelets (1.80 (1.19-2.71)), and quetiapine (0.31 (0.12-0.81)). Specific high-risk factors in the pre-frail cohort are Barthel's score (120 (7.7-1700)), Pfeiffer test (8.4; (2.3-31)), Mini Nutritional Assessment (MNA) (1200 (18-88,000)), constipation (0.025 (0.0027-0.24)), falls (18,000 (150-2,200,000)), deep venous thrombosis (8400 (19-3,700,000)), cerebrovascular disease (0.01 (0.00064-0.16)), diabetes (360 (3.4-39,000)), thyroid disease (0.00099 (0.000012-0.085)), and the use of PPIs (0.062 (0.0072-0.54)), Zolpidem (0.000014 (0.0000000021-0.092)), antidiabetics (0.00015 (0.00000042-0.051)), diuretics (0.0003 (0.000004-0.022)), and opiates (0.000069 (0.00000035-0.013)).ConclusionsFrailty is associated with higher mortality at two years than pre-frailty. Frailty is recognized as a systemic syndrome with many links to older-age comorbidities, which are also found in our study. Polypharmacy is strongly associated with frailty, and several commonly prescribed drugs are strongly associated with increased mortality. It must be considered that frail patients need coordinated attention where the diverse specialist taking care of them jointly examines the interactions between the diversity of treatments prescribed.
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Project description:AimsTo compare the effectiveness of allopurinol with no treatment or placebo for the prevention of cardiovascular events in hyperuricemic patients.Methods and resultsPubmed, Web of Science and Cochrane library were searched from inception until July 2020. Randomized controlled trials (RCT) and observational studies in hyperuricemic patients without significant renal disease and treated with allopurinol, versus placebo or no treatment were included. Outcome measures were cardiovascular mortality, myocardial infarction, stroke, or a combined endpoint (CM/MI/S). For RCT's a random effects meta-analysis was performed. For observational studies a narrative synthesis was performed. Of the original 1995 references we ultimately included 26 RCT's and 21 observational studies. We found a significantly reduced risk of combined endpoint (Risk Ratio 0.65 [95% CI] [0.46 to 0.91]; p = 0.012) and myocardial infarction (RR 0.47 [0.27 to 0.80]; p = 0.01) in the allopurinol group compared to controls. We found no significant effect of allopurinol on stroke or cardiovascular mortality. Of the 15 observational studies with sufficient quality, allopurinol was associated with reduced cardiovascular mortality in 1 out of 3 studies that reported this outcome, myocardial infarction in 6 out of 8, stroke in 4 out of 7, and combined end-point in 2 out of 2. Cardiovascular benefit was only observed when allopurinol therapy was prolonged for more than 6 months and when an appropriate allopurinol dose was administered (300 mg or more/day) or sufficient reduction of serum urate concentration was achieved (<0.36 mmol/l).ConclusionsData from RCT's and observational studies indicate that allopurinol treatment reduces cardiovascular risk in patients with hyperuricemia. However, the quality of evidence from RCTs is low to moderate. To establish whether allopurinol lowers the risk of cardiovascular events a well-designed and adequately powered randomized, placebo-controlled trial is needed in high-risk patients with hyperuricemia.Systematic review registrationPROSPERO registration CRD42018089744.
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Project description:BackgroundBlood pressure (BP) management in frail older people is challenging. An randomised controlled trial of largely non-frail older people found cardiovascular and mortality benefit with systolic (S) BP target <120 mmHg. However, all-cause mortality by attained BP in routine care in frail adults aged above 75 is unclear.ObjectivesTo estimate observational associations between baseline BP and mortality/cardiovascular outcomes in a primary-care population aged above 75, stratified by frailty.MethodsProspective observational analysis using electronic health records (clinical practice research datalink, n = 415,980). We tested BP associations with cardiovascular events and mortality using competing and Cox proportional-hazards models respectively (follow-up ≤10 years), stratified by baseline electronic frailty index (eFI: fit (non-frail), mild, moderate, severe frailty), with sensitivity analyses on co-morbidity, cardiovascular risk and BP trajectory.ResultsRisks of cardiovascular outcomes increased with SBPs >150 mmHg. Associations with mortality varied between non-frail <85 and frail 75-84-year-olds and all above 85 years. SBPs above the 130-139-mmHg reference were associated with lower mortality risk, particularly in moderate to severe frailty or above 85 years (e.g. 75-84 years: 150-159 mmHg Hazard Ratio (HR) mortality compared to 130-139: non-frail HR = 0.94, 0.92-0.97; moderate/severe frailty HR = 0.84, 0.77-0.92). SBP <130 mmHg and Diastolic(D)BP <80 mmHg were consistently associated with excess mortality, independent of BP trajectory toward the end of life.ConclusionsIn representative primary-care patients aged ≥75, BP <130/80 was associated with excess mortality. Hypertension was not associated with increased mortality at ages above 85 or at ages 75-84 with moderate/severe frailty, perhaps due to complexities of co-existing morbidities. The priority given to aggressive BP reduction in frail older people requires further evaluation.
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Project description:IntroductionThe emerging epidemiological evidence of increased cardiovascular disease (CVD) risk among persons diagnosed with tuberculosis (TB) has not been systematically reviewed to date. Our aim was to review the existing epidemiological evidence for elevated risk of CVD morbidity and mortality among persons diagnosed with TB compared to controls.Materials and methodsEMBASE, MEDLINE, and Cochrane databases were searched (inception to January 2020) for terms related to "tuberculosis" and "cardiovascular diseases". Inclusion criteria: trial, cohort, or case-control study design; patient population included persons diagnosed with TB infection or disease; relative risk (RR) estimate and confidence interval reported for CVD morbidity or mortality compared to suitable controls. Exclusion criteria: no TB or CVD outcome definition; duplicate study; non-English abstract; non-human participants. Two reviewers screened studies, applied ROBINS-I tool to assess risk of bias, and extracted data independently. Random effects meta-analysis estimated a pooled RR of CVD morbidity and mortality for persons diagnosed with TB compared to controls.Results6,042 articles were identified, 244 full texts were reviewed, and 16 were included, meta-analyzing subsets of 8 studies' RR estimates. We estimated a pooled RR of 1.51 (95% CI: 1.16-1.97) for major adverse cardiac events among those diagnosed with TB compared to non-TB controls (p = 0.0024). A 'serious' pooled risk of bias was found across studies with between-study heterogeneity (I2 = 75.3%).ConclusionsTB appears to be a marker for increased CVD risk; however, the literature is limited and is accompanied by serious risk of confounding bias and evidence of publication bias. Further retrospective and prospective studies are needed. Pending this evidence, best practice may be to consider persons diagnosed with TB at higher risk of CVD as a precautionary measure.
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Project description:The widespread adoption of digital health technologies such as smartphone-based mobile applications, wearable activity trackers and Internet of Things systems has rapidly enabled new opportunities for predictive health monitoring. Leveraging digital health tools to track parameters relevant to human health is particularly important for the older segments of the population as old age is associated with multimorbidity and higher care needs. In order to assess the potential of these digital health technologies to improve health outcomes, it is paramount to investigate which digitally measurable parameters can effectively improve health outcomes among the elderly population. Currently, there is a lack of systematic evidence on this topic due to the inherent heterogeneity of the digital health domain and the lack of clinical validation of both novel prototypes and marketed devices. For this reason, the aim of the current study is to synthesize and systematically analyse which digitally measurable data may be effectively collected through digital health devices to improve health outcomes for older people. Using a modified PICO process and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework, we provide the results of a systematic review and subsequent meta-analysis of digitally measurable predictors of morbidity, hospitalization, and mortality among older adults aged 65 or older. These findings can inform both technology developers and clinicians involved in the design, development and clinical implementation of digital health technologies for elderly citizens.
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Project description:BACKGROUND:As the number of older adults increases, so does the number of frail older adults. Although anthropometry has been widely used as a way to stratify the overall mortality risk of a person, the significance of these measurements becomes blurred in the case of frail older adults who have changes in body composition. Therefore, the aim of this study is to determine the association of anthropometric measurements (body mass index, knee-adjusted height body mass index, waist-to-hip ratio and calf circumference) with mortality risk in a group of older Mexican adults. METHODS:This is a longitudinal analysis of the Mexican Health and Aging sub-sample (with biomarkers, n = 2573) from the first wave in 2001, followed-up to the last available wave in 2015. Only frail 50-year or older adults (Frailty Index with a cut-off value of 0.21 or higher, was used) were considered for this analysis (n = 1298). A survival analysis was performed with Kaplan-Meier curves and Cox regression models (unadjusted and adjusted for confounding). Socio-demographic, health risks, physical activity and comorbidities were variables used for adjusting the multivariate models. RESULTS:From the total sample of 1298 older adults, 32.5% (n = 422) died during follow-up. The highest hazard ratio in the adjusted model was for calf circumference 1.31 (95% confidence interval 1.02-1.69, p = 0.034). Other measurements were not significant. CONCLUSIONS:Anthropometric measurements have different significance in frail older adults, and these differences could have implications on adverse outcomes. Calf circumference has a potential value in predicting negative health outcomes.
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Project description:BackgroundHome visits for older adults aim to prevent cognitive and functional impairment, thus reducing institutionalization and mortality. Visitors may provide information, investigate untreated problems, encourage medication compliance, and provide referrals to services.Methods and findingsData sourcesTen databases including CENTRAL and Medline searched through December 2012.Study selectionRandomized controlled trials enrolling community-dwelling persons without dementia aged over 65 years. Interventions included visits at home by a health or social care professional that were not related to hospital discharge.Data extraction and synthesisTwo authors independently extracted data. Outcomes were pooled using random effects.Main outcomes and measuresMortality, institutionalization, hospitalization, falls, injuries, physical functioning, cognitive functioning, quality of life, and psychiatric illness.ResultsSixty-four studies with 28642 participants were included. Home visits were not associated with absolute reductions in mortality at longest follow-up, but some programs may have small relative effects (relative risk?=?0.93 [0.87 to 0.99]; absolute risk?=?0.00 [-0.01 to 0.00]). There was moderate quality evidence of no overall effect on the number of people institutionalized (RR?=?1.02 [0.88 to 1.18]) or hospitalized (RR?=?0.96 [0.91 to 1.01]). There was high quality evidence for number of people who fell, which is consistent with no effect or a small effect (odds ratio?=?0.86 [0.73 to 1.01]), but there was no evidence that these interventions increased independent living. There was low and very low quality evidence of effects for quality of life (standardised mean difference?=?-0.06 [-0.11 to -0.01]) and physical functioning (SMD?=?-0.10 [-0.17 to -0.03]) respectively, but these may not be clinically important.ConclusionsHome visiting is not consistently associated with differences in mortality or independent living, and investigations of heterogeneity did not identify any programs that are associated with consistent benefits. Due to poor reporting of intervention components and delivery, we cannot exclude the possibility that some programs may be effective.
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Project description:BackgroundCardiovascular disease is an important driver of the increased mortality associated with chronic kidney disease (CKD). Higher left ventricular mass (LVM) predicts increased risk of adverse cardiovascular outcomes and total mortality, but previous reviews have shown no clear association between intervention-induced LVM change and all-cause or cardiovascular mortality in CKD.MethodsThe primary objective of this meta-analysis was to investigate whether treatment-induced reductions in LVM over periods ≥12 months were associated with all-cause mortality in patients with CKD. Cardiovascular mortality was investigated as a secondary outcome. Measures of association in the form of relative risks (RRs) with associated variability and precision (95% confidence intervals [CIs]) were extracted directly from each study, when reported, or were calculated based on the published data, if possible, and pooled RR estimates were determined.ResultsThe meta-analysis included 42 trials with duration ≥12 months: 6 of erythropoietin stimulating agents treating to higher vs. lower hemoglobin targets, 10 of renin-angiotensin-aldosterone system inhibitors vs. placebo or another blood pressure lowering agent, 14 of modified hemodialysis regimens, and 12 of other types of interventions. All-cause mortality was reported in 121/2584 (4.86%) subjects in intervention groups and 168/2606 (6.45%) subjects in control groups. The pooled RR estimate of the 27 trials ≥12 months with ≥1 event in ≥1 group was 0.72 (95% CI 0.57 to 0.90, p = 0.005), with little heterogeneity across studies. Directionalities of the associations in intervention subgroups were the same. Sensitivity analyses of ≥6 months (34 trials), ≥9 months (29 trials), and >12 months (10 trials), and including studies with no events in either group, demonstrated similar risk reductions to the primary analysis. The point estimate for cardiovascular mortality was similar to all-cause mortality, but not statistically significant: RR 0.67, 95% CI 0.39 to 1.16.ConclusionsThese results suggest that LVM regression may be a useful surrogate marker for benefits of interventions intended to reduce mortality risk in patients with CKD.
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