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1.
Eur J Prev Cardiol ; 28(13): 1460-1466, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34695217

RESUMO

AIMS: Smoking is a major preventable risk factor for cardiovascular disease and mortality. However, the 'smoker's paradox' suggests that it is associated with better survival after acute myocardial infarction. We aimed to investigate the impact of smoking on mortality and cardiovascular outcomes in patients with stable coronary artery disease. METHODS: The international CLARIFY registry included 32,703 patients with stable coronary artery disease between 2009 and 2010. Among the 32,378 patients included in the present analysis, Cox proportional hazards models (adjusted for age, sex, geographic region, prior myocardial infarction, and revascularization status) were used to estimate associations between smoking status and outcomes. Patients were stratified as follows: 41.3% of patients never smoked, 12.5% were current smokers and 46.2% were former smokers. RESULTS: Current smokers were younger than never-smokers and former smokers (59 vs. 66 and 64 years old, respectively, p < 0.0001). There were more men among current or former smokers compared with never-smokers. Compared with never-smokers, both current and former smokers were at higher risk of all-cause death (hazard ratio = 1.96 and 1.37) and cardiovascular death (hazard ratio = 1.92 and 1.38) within five years (all p < 0.05). Similarly graded and increased risks were present for myocardial infarction and the composite of cardiovascular death, myocardial infarction and stroke (all p < 0.05). CONCLUSION: In contrast to the 'smoker's paradox', current smokers with stable coronary artery disease have a greatly increased risk of future cardiovascular events, including mortality, compared with never-smokers. In former smokers, cardiovascular risk remains elevated albeit at an intermediate level between that of current and never-smokers, reinforcing the importance of smoking cessation. (ISRCTN43070564).

2.
ESC Heart Fail ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34480422

RESUMO

AIMS: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. METHODS AND RESULTS: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 × 10-8 under an additive genetic model. CONCLUSIONS: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.

4.
BMJ Open ; 11(8): e046441, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446484

RESUMO

OBJECTIVES: There is a lack of evidence to inform the delivery and follow-up of bariatric surgery for people with severe obesity. The SurgiCal Obesity Treatment Study (SCOTS) is a national longitudinal cohort of people undergoing bariatric surgery. Here, we describe characteristics of the recruited SCOTS cohort, and the relationship between health and socioeconomic status with body mass index (BMI) and age. PARTICIPANTS/METHODS: 445 participants scheduled for bariatric surgery at any of 14 centres in Scotland, UK, were recruited between 2013 and 2016 for this longitudinal cohort study (1 withdrawal); 249 completed health-related preoperative patient-reported outcome measures. Regression models were used to estimate the effect of a 10-unit increase in age or BMI, adjusting for sex, smoking and socioeconomic status. RESULTS: Mean age was 46 years and median BMI was 47 kg/m2. For each 10 kg/m2 higher BMI, there was a change of -5.2 (95% CI -6.9 to -3.5; p<0.0001) in Rand 12-item Short Form Survey Physical Component Summary (SF-12 PCS), -0.1 (95% CI -0.2 to -0.1; p<0.0001) in EuroQoL 5-level EQ-5D version index score and 14.2 (95% CI 10.7 to 17.7; p<0.0001) in Impact of Weight on Quality of Life-Lite Physical Function Score. We observed a 3.1 times higher use of specialist aids and equipment at home (OR: 3.1, 95% CI 1.9 to 5.0; p<0.0001). Broadly, similar results were seen for each 10-year higher age, including a change of -2.1 (95% CI -3.7 to -0.5; p<0.01) in SF-12 PCS. CONCLUSIONS: A higher BMI combined with older age is associated with poor physical functioning and quality of life in people seeking bariatric surgery treatment. Policy-makers must consider the health and care needs of these individuals and invest to provide increased access to effective weight management. TRIAL REGISTRATION NUMBER: ISRCTN47072588.


Assuntos
Obesidade Mórbida , Idoso , Estudos de Coortes , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/cirurgia , Obesidade Mórbida/cirurgia , Estudos Prospectivos , Qualidade de Vida , Escócia/epidemiologia , Fatores Socioeconômicos , Reino Unido
5.
Kidney Int Rep ; 6(8): 2159-2170, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34386665

RESUMO

Introduction: Whether clinically implementable exercise interventions in people receiving hemodialysis (HD) therapy improve health-related quality of life (HRQoL) remains unknown. The PrEscription of intraDialytic exercise to improve quAlity of Life (PEDAL) study evaluated the clinical benefit and cost-effectiveness of a 6-month intradialytic exercise program. Methods: In a multicenter, single-blinded, randomized, controlled trial, people receiving HD were randomly assigned to (i) intradialytic exercise training (exercise intervention group [EX]) and (ii) usual care (control group [CON]). Primary outcome was change in Kidney Disease Quality of Life Short-Form Physical Component Summary (KDQOL-SF 1.3 PCS) from baseline to 6 months. Cost-effectiveness was determined using health economic analysis; physiological impairment was evaluated by peak oxygen uptake; and harms were recorded. Results: We randomized 379 participants; 335 and 243 patients (EX n = 127; CON n = 116) completed baseline and 6-month assessments, respectively. Mean difference in change PCS from baseline to 6 months between EX and CON was 2.4 (95% confidence interval [CI]: -0.1 to 4.8) arbitrary units (P = 0.055); no improvements were observed in peak oxygen uptake or secondary outcome measures. Participants in the intervention group had poor compliance (47%) and poor adherence (18%) to the exercise prescription. Cost of delivering intervention ranged from US$598 to US$1092 per participant per year. The number of participants with harms was similar between EX (n = 69) and CON (n = 56). A primary limitation was the lack of an attention CON. Many patients also withdrew from the study or were too unwell to complete all physiological outcome assessments. Conclusions: A 6-month intradialytic aerobic exercise program was not clinically beneficial in improving HRQoL as delivered to this cohort of deconditioned patients on HD.

6.
Eur Heart J ; 42(37): 3844-3852, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34269376

RESUMO

AIMS: Fractional flow reserve (FFRCT) using computed tomography coronary angiography (CTCA) determines both the presence of coronary artery disease and vessel-specific ischaemia. We tested whether an evaluation strategy based on FFRCT would improve economic and clinical outcomes compared with standard care. METHODS AND RESULTS: Overall, 1400 patients with stable chest pain in 11 centres were randomized to initial testing with CTCA with selective FFRCT (experimental group) or standard clinical care pathways (standard group). The primary endpoint was total cardiac costs at 9 months. Secondary endpoints were angina status, quality of life, major adverse cardiac and cerebrovascular events, and use of invasive coronary angiography. Randomized groups were similar at baseline. Most patients had an initial CTCA: 439 (63%) in the standard group vs. 674 (96%) in the experimental group, 254 of whom (38%) underwent FFRCT. Mean total cardiac costs were higher by £114 (+8%) in the experimental group, with a 95% confidence interval from -£112 (-8%) to +£337 (+23%), though the difference was not significant (P = 0.10). Major adverse cardiac and cerebrovascular events did not differ significantly (10.2% in the experimental group vs. 10.6% in the standard group) and angina and quality of life improved to a similar degree over follow-up in both randomized groups. Invasive angiography was reduced significantly in the experimental group (19% vs. 25%, P = 0.01). CONCLUSION: A strategy of CTCA with selective FFRCT in patients with stable angina did not differ significantly from standard clinical care pathways in cost or clinical outcomes, but did reduce the use of invasive coronary angiography.


Assuntos
Angina Estável , Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Angina Estável/diagnóstico por imagem , Angina Estável/terapia , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários , Humanos , Valor Preditivo dos Testes , Qualidade de Vida
7.
Circulation ; 144(7): 512-523, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34261331

RESUMO

BACKGROUND: Although angina is common in patients with stable coronary artery disease, limited data are available on its prevalence, natural evolution, and outcomes in the era of effective cardiovascular drugs and widespread use of coronary revascularization. METHODS: Using data from 32 691 patients with stable coronary artery disease from the prospective observational CLARIFY registry (Prospective Observational Longitudinal Registry of Patients with Stable Coronary Artery Disease), anginal status was mapped each year in patients without new coronary revascularization or new myocardial infarction. The use of medical interventions in the year preceding angina resolution was explored. The effect of 1-year changes in angina status on 5-year outcomes was analyzed using multivariable analysis. RESULTS: Among 7212 (22.1%) patients who reported angina at baseline, angina disappeared (without coronary revascularization) in 39.6% at 1 year, with further annual decreases. In patients without angina at baseline, 2.0% to 4.8% developed angina each year. During 5-year follow-up, angina was controlled in 7773 patients, in whom resolution of angina was obtained with increased use of antianginal treatment in 11.1%, with coronary revascularization in 4.5%, and without any changes in medication or revascularization in 84.4%. Compared to patients without angina at baseline and 1 year, persistence of angina and occurrence of angina at 1 year with conservative management were each independently associated with higher rates of cardiovascular death or myocardial infarction (adjusted hazard ratio, 1.32 [95% CI, 1.12-1.55] for persistence of angina; adjusted hazard ratio, 1.37 [95% CI, 1.11-1.70] for occurrence of angina) at 5 years. Patients whose angina had resolved at 1 year with conservative management were not at higher risk of cardiovascular death or myocardial infarction than those who never experienced angina (adjusted hazard ratio, 0.97 [95% CI, 0.82-1.15]). CONCLUSIONS: Angina affects almost one-quarter of patients with stable coronary artery disease but resolves without events or coronary revascularization in most patients. Resolution of angina within 1 year with conservative management predicted outcomes similar to lack of angina, whereas persistence or occurrence was associated with worse outcomes. Because most patients with angina are likely to experience resolution of symptoms, and because there is no demonstrated outcome benefit to routine revascularization, this study emphasizes the value of conservative management of stable coronary artery disease. Registration: URL: https://www.isrctn.com; Unique identifier: ISRCTN43070564.

8.
JACC Heart Fail ; 9(7): 518-527, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34119470

RESUMO

OBJECTIVES: This study sought to examine the effect of intravenous iron on heart failure events in hemodialysis patients. BACKGROUND: Heart failure is a common and deadly complication in patients receiving hemodialysis and is difficult to diagnose and treat. METHODS: The study analyzed heart failure events in the PIVOTAL (Proactive IV Iron Therapy in Hemodialysis Patients) trial, which compared intravenous iron administered proactively in a high-dose regimen with a low-dose regimen administered reactively. Heart failure hospitalization was an adjudicated outcome, a component of the primary composite outcome, and a prespecified secondary endpoint in the trial. RESULTS: Overall, 2,141 participants were followed for a median of 2.1 years. A first fatal or nonfatal heart failure event occurred in 51 (4.7%) of 1,093 patients in the high-dose iron group and in 70 (6.7%) of 1,048 patients in the low-dose group (HR: 0.66; 95% CI: 0.46-0.94; P = 0.023). There was a total of 63 heart failure events (including first and recurrent events) in the high-dose iron group and 98 in the low-dose group, giving a rate ratio of 0.59 (95% CI: 0.40-0.87; P = 0.0084). Most patients presented with pulmonary edema and were mainly treated by mechanical removal of fluid. History of heart failure and diabetes were independent predictors of a heart failure event. CONCLUSIONS: Compared with a lower-dose regimen, high-dose intravenous iron decreased the occurrence of first and recurrent heart failure events in patients undergoing hemodialysis, with large relative and absolute risk reductions. (UK Multicentre Open-label Randomised Controlled Trial Of IV Iron Therapy In Incident Haemodialysis Patients; 2013-002267-25).


Assuntos
Insuficiência Cardíaca , Administração Intravenosa , Adulto , Hospitalização , Humanos , Ferro , Diálise Renal
9.
Health Technol Assess ; 25(40): 1-52, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34156335

RESUMO

BACKGROUND: Whether or not clinically implementable exercise interventions in haemodialysis patients improve quality of life remains unknown. OBJECTIVES: The PEDAL (PrEscription of intraDialytic exercise to improve quAlity of Life in patients with chronic kidney disease) trial evaluated the clinical effectiveness and cost-effectiveness of a 6-month intradialytic exercise programme on quality of life compared with usual care for haemodialysis patients. DESIGN: We conducted a prospective, multicentre randomised controlled trial of haemodialysis patients from five haemodialysis centres in the UK and randomly assigned them (1 : 1) using a web-based system to (1) intradialytic exercise training plus usual-care maintenance haemodialysis or (2) usual-care maintenance haemodialysis. SETTING: The setting was five dialysis units across the UK from 2015 to 2019. PARTICIPANTS: The participants were adult patients with end-stage kidney disease who had been receiving haemodialysis therapy for > 1 year. INTERVENTIONS: Participants were randomised to receive usual-care maintenance haemodialysis or usual-care maintenance haemodialysis plus intradialytic exercise training. MAIN OUTCOME MEASURES: The primary outcome of the study was change in Kidney Disease Quality of Life Short Form, version 1.3, physical component summary score (from baseline to 6 months). Cost-effectiveness was determined using health economic analysis and the EuroQol-5 Dimensions, five-level version. Additional secondary outcomes included quality of life (Kidney Disease Quality of Life Short Form, version 1.3, generic multi-item and burden of kidney disease scales), functional capacity (sit-to-stand 60 and 10-metre Timed Up and Go tests), physiological measures (peak oxygen uptake and arterial stiffness), habitual physical activity levels (measured by the International Physical Activity Questionnaire and Duke Activity Status Index), fear of falling (measured by the Tinetti Falls Efficacy Scale), anthropometric measures (body mass index and waist circumference), clinical measures (including medication use, resting blood pressure, routine biochemistry, hospitalisations) and harms associated with intervention. A nested qualitative study was conducted. RESULTS: We randomised 379 participants; 335 patients completed baseline assessments and 243 patients (intervention, n = 127; control, n = 116) completed 6-month assessments. The mean difference in change in physical component summary score from baseline to 6 months between the intervention group and control group was 2.4 arbitrary units (95% confidence interval -0.1 to 4.8 arbitrary units; p = 0.055). Participants in the intervention group had poor compliance (49%) and very poor adherence (18%) to the exercise prescription. The cost of delivering the intervention ranged from £463 to £848 per participant per year. The number of participants with harms was similar in the intervention (n = 69) and control (n = 56) groups. LIMITATIONS: Participants could not be blinded to the intervention; however, outcome assessors were blinded to group allocation. CONCLUSIONS: On trial completion the primary outcome (Kidney Disease Quality of Life Short Form, version 1.3, physical component summary score) was not statistically improved compared with usual care. The findings suggest that implementation of an intradialytic cycling programme is not an effective intervention to enhance health-related quality of life, as delivered to this cohort of deconditioned patients receiving haemodialysis. FUTURE WORK: The benefits of longer interventions, including progressive resistance training, should be confirmed even if extradialytic delivery is required. Future studies also need to evaluate whether or not there are subgroups of patients who may benefit from this type of intervention, and whether or not there is scope to optimise the exercise intervention to improve compliance and clinical effectiveness. TRIAL REGISTRATION: Current Controlled Trials ISRCTN83508514. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 40. See the NIHR Journals Library website for further project information.


Assuntos
Falência Renal Crônica , Qualidade de Vida , Acidentes por Quedas , Análise Custo-Benefício , Exercício Físico , Terapia por Exercício , Medo , Humanos , Falência Renal Crônica/terapia , Estudos Prospectivos , Diálise Renal
10.
Clin Kidney J ; 14(5): 1345-1355, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33959264

RESUMO

Background: Exercise interventions designed to improve physical function and reduce sedentary behaviour in haemodialysis (HD) patients might improve exercise capacity, reduce fatigue and lead to improved quality of life (QOL). The PrEscription of intraDialytic exercise to improve quAlity of Life study aimed to evaluate the effectiveness of a 6-month intradialytic exercise programme on QOL and physical function, compared with usual care for patients on HD in the UK. Methods: We conducted a prospective, pragmatic multicentre randomized controlled trial in 335 HD patients and randomly (1:1) assigned them to either (i) intradialytic exercise training plus usual care maintenance HD or (ii) usual care maintenance HD. The primary outcome of the study was the change in Kidney Disease Quality of Life Short Form (KDQOL-SF 1.3) Physical Component Score between baseline and 6 months. Additional secondary outcomes included changes in peak aerobic capacity, physical fitness, habitual physical activity levels and falls (International Physical Activity Questionnaire, Duke's Activity Status Index and Tinetti Falls Efficacy Scale), QOL and symptom burden assessments (EQ5D), arterial stiffness (pulse wave velocity), anthropometric measures, resting blood pressure, clinical chemistry, safety and harms associated with the intervention, hospitalizations and cost-effectiveness. A nested qualitative study investigated the experience and acceptability of the intervention for both participants and members of the renal health care team. Results: At baseline assessment, 62.4% of the randomized cohort were male, the median age was 59.3 years and 50.4% were white. Prior cerebrovascular events and myocardial infarction were present in 8 and 12% of the cohort, respectively, 77.9% of patients had hypertension and 39.4% had diabetes. Baseline clinical characteristics and laboratory data for the randomized cohort were generally concordant with data from the UK Renal Registry. Conclusion: The results from this study will address a significant knowledge gap in the prescription of exercise interventions for patients receiving maintenance HD therapy and inform the development of intradialytic exercise programmes both nationally and internationally. Trial Registration: ISRCTN N83508514; registered on 17 December 2014.

11.
Am J Cardiol ; 150: 40-46, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34011435

RESUMO

Left Bundle Branch Block (LBBB) is a frequently encountered electrical abnormality in patients with chronic (more than 3 months after myocardial infarction, or evidence of coronary artery disease with ischemia) coronary syndromes (CCS), but its prognostic significance remains unclear. We aimed to describe the prevalence, incidence and five-year outcomes of LBBB in outpatients with CCS using the CLARIFY registry. Main outcome was a composite of CV death, MI or stroke. Secondary outcomes included all cause death, hospitalization for heart failure (HF) and permanent pacemaker implantation. Among 23.544 patients with available information regarding LBBB status at baseline, 1.041 (4.4%) had LBBB at baseline and 1.015 (4.5%) patients developed a new LBBB during 5-year follow-up. In multivariate analysis, LBBB at baseline was not associated with the composite outcome of CV death, MI or stroke (HR 1.06, 95% CI [0.86 - 1.31], p = 0.67) or the risk of all-cause death (HR 1.07, 95% CI [0.87 - 1.32], p = 0.52) but was significantly associated with a higher risk of hospitalization for HF (HR 1.50, 95% CI [1.21 - 1.88], p < 0.001) and permanent pacemaker implantation (HR 2.11, 95% CI [1.45 - 3.07], p < 0.001). The main factors associated with new-onset LBBB were male sex (HR 0.8 [0.66-0.98], p = 0.028) history of atrial fibrillation (HR 1.29, 95% CI [1.01 - 1.64], p = 0.04), CABG (HR 1.27, [1.08 - 1.51], p = 0.004) and MI (HR 1.19, 95% CI [1.01 - 1.40], p = 0.034). In conclusion, in a contemporary registry of outpatients with CCS, the prevalence of LBBB was 4.4% and the additional 5-years incidence 6.2%. LBBB, in itself, was not associated with a higher risk of major adverse cardiovascular events or all cause mortality. It was however an independent predictor of risk of hospitalization for heart failure and permanent pacemaker implantation.


Assuntos
Bloqueio de Ramo/epidemiologia , Doença das Coronárias/complicações , Idoso , Bloqueio de Ramo/mortalidade , Bloqueio de Ramo/terapia , Causas de Morte , Doença Crônica , Doença das Coronárias/mortalidade , Doença das Coronárias/terapia , Eletrocardiografia , Feminino , França/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Marca-Passo Artificial , Prevalência , Prognóstico , Estudos Prospectivos , Sistema de Registros , Acidente Vascular Cerebral/epidemiologia , Síndrome
12.
BMC Med ; 19(1): 69, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33731105

RESUMO

BACKGROUND: Sleep traits are associated with cardiometabolic disease risk, with evidence from Mendelian randomization (MR) suggesting that insomnia symptoms and shorter sleep duration increase coronary artery disease risk. We combined adjusted multivariable regression (AMV) and MR analyses of phenotypes of unfavourable sleep on 113 metabolomic traits to investigate possible biochemical mechanisms linking sleep to cardiovascular disease. METHODS: We used AMV (N = 17,368) combined with two-sample MR (N = 38,618) to examine effects of self-reported insomnia symptoms, total habitual sleep duration, and chronotype on 113 metabolomic traits. The AMV analyses were conducted on data from 10 cohorts of mostly Europeans, adjusted for age, sex, and body mass index. For the MR analyses, we used summary results from published European-ancestry genome-wide association studies of self-reported sleep traits and of nuclear magnetic resonance (NMR) serum metabolites. We used the inverse-variance weighted (IVW) method and complemented this with sensitivity analyses to assess MR assumptions. RESULTS: We found consistent evidence from AMV and MR analyses for associations of usual vs. sometimes/rare/never insomnia symptoms with lower citrate (- 0.08 standard deviation (SD)[95% confidence interval (CI) - 0.12, - 0.03] in AMV and - 0.03SD [- 0.07, - 0.003] in MR), higher glycoprotein acetyls (0.08SD [95% CI 0.03, 0.12] in AMV and 0.06SD [0.03, 0.10) in MR]), lower total very large HDL particles (- 0.04SD [- 0.08, 0.00] in AMV and - 0.05SD [- 0.09, - 0.02] in MR), and lower phospholipids in very large HDL particles (- 0.04SD [- 0.08, 0.002] in AMV and - 0.05SD [- 0.08, - 0.02] in MR). Longer total sleep duration associated with higher creatinine concentrations using both methods (0.02SD per 1 h [0.01, 0.03] in AMV and 0.15SD [0.02, 0.29] in MR) and with isoleucine in MR analyses (0.22SD [0.08, 0.35]). No consistent evidence was observed for effects of chronotype on metabolomic measures. CONCLUSIONS: Whilst our results suggested that unfavourable sleep traits may not cause widespread metabolic disruption, some notable effects were observed. The evidence for possible effects of insomnia symptoms on glycoprotein acetyls and citrate and longer total sleep duration on creatinine and isoleucine might explain some of the effects, found in MR analyses of these sleep traits on coronary heart disease, which warrant further investigation.


Assuntos
Doença da Artéria Coronariana , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Doenças Metabólicas , Sono , Idoso , Doença da Artéria Coronariana/epidemiologia , Creatinina/metabolismo , Estudos Transversais , Humanos , Isoleucina/metabolismo , Doenças Metabólicas/complicações , Doenças Metabólicas/epidemiologia , Fenótipo , Polimorfismo de Nucleotídeo Único , Fatores de Risco
13.
Clin Res Cardiol ; 110(8): 1299-1307, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33755777

RESUMO

BACKGROUND: The recent AFFIRM-AHF trial assessing the effect of intravenous (IV) iron on outcomes in patients hospitalised with worsening heart failure who had iron deficiency (ID) narrowly missed its primary efficacy endpoint of recurrent hospitalisations for heart failure (HHF) or cardiovascular (CV) death. We conducted a meta-analysis to determine whether these results were consistent with previous trials. METHODS: We searched for randomised trials of patients with heart failure investigating the effect of IV iron vs placebo/control groups that reported HHF and CV mortality from 1st January 2000 to 5th December 2020. Seven trials were identified and included in this analysis. A fixed effect model was applied to assess the effects of IV iron on the composite of first HHF or CV mortality and individual components of these. RESULTS: Altogether, 2,166 patients were included (n = 1168 assigned to IV iron; n = 998 assigned to control). IV iron reduced the composite of HHF or CV mortality substantially [OR 0.73; (95% confidence interval 0.59-0.90); p = 0.003]. Outcomes were consistent for the pooled trials prior to AFFIRM-AHF. Whereas first HHF were reduced substantially [OR 0.67; (0.54-0.85); p = 0.0007], the effect on CV mortality was uncertain but appeared smaller [OR 0.89; (0.66-1.21); p = 0.47]. CONCLUSION: Administration of IV iron to patients with heart failure and ID reduces the risk of the composite outcome of first heart failure hospitalisation or cardiovascular mortality, but this outcome may be driven predominantly by an effect on HHF. At least three more substantial trials of intravenous iron are underway.

14.
Open Heart ; 8(1)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33637568

RESUMO

BACKGROUND: Coronary artery bypass graft (CABG) patients are under-represented in acute coronary syndrome (ACS) trials. We compared characteristics and outcomes for patients who did and did not participate in a randomised trial of invasive versus non-invasive management (CABG-ACS). METHODS: ACS patients with prior CABG in four hospitals were randomised to invasive or non-invasive management. Non-randomised patients entered a registry. Primary efficacy (composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction (MI), heart failure) and safety outcomes (composite of bleeding, stroke, procedure-related MI, worsening renal function) were independently adjudicated. RESULTS: Of 217 patients screened, 84 (39%) screenfailed, of whom 24 (29%) did not consent and 60 (71%) were ineligible. Of 133 (61%) eligible, 60 (mean±SD age, 71±9 years, 72% male) entered the trial and 73 (age, 72±10 years, 73% male) entered a registry (preferences: physician (79%), patient (38%), both (21%)).Compared with trial participants, registry patients had more valve disease, lower haemoglobin, worse New York Heart Association class and higher frailty.At baseline, invasive management was performed in 52% and 49% trial and registry patients, respectively, of whom 32% and 36% had percutaneous coronary intervention at baseline, respectively (p=0.800). After 2 years follow-up (694 (median, IQR 558-841) days), primary efficacy (43% trial vs 49% registry (HR 1.14, 95% CI 0.69 to 1.89)) and safety outcomes (28% trial vs 22% registry (HR 0.74, 95% CI 0.37 to 1.46)) were similar. EuroQol was lower in registry patients at 1 year. CONCLUSIONS: Compared with trial participants, registry participants had excess morbidity, but longer-term outcomes were similar. TRIAL REGISTRATION NUMBER: NCT01895751.


Assuntos
Síndrome Coronariana Aguda/terapia , Ponte de Artéria Coronária/métodos , Fibrinolíticos/uso terapêutico , Cuidados Pré-Operatórios/métodos , Sistema de Registros , Terapia Trombolítica/métodos , Idoso , Feminino , Humanos , Masculino , Resultado do Tratamento
15.
Diabetes Obes Metab ; 23(6): 1371-1378, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33591613

RESUMO

AIM: To determine whether metformin's effects on carotid artery intima-media thickness (cIMT) in type 1 diabetes differ according to smoking status. METHODS: Regression model effect estimates for the effect of metformin versus placebo (double-blind) on carotid IMT were calculated as a subgroup analysis of the REMOVAL trial. RESULTS: In 428 randomized participants (227 never-smokers, 201 ever-smokers), averaged mean carotid IMT progression (per year) was reduced by metformin versus placebo in never-smokers (-0.012 mm, 95% CI -0.021 to -0.002; p = .0137) but not in ever-smokers (0.003 mm, 95% CI -0.008 to 0.014; p = .5767); and similarly in non-current smokers (-0.008 mm, 95% CI -0.015 to -0.00001; p = .0497) but not in current smokers (0.013 mm, 95% CI -0.007 to 0.032; p = .1887). Three-way interaction terms (treatment*time*smoking status) were significant for never versus ever smoking (p = .0373, prespecified) and non-current versus current smoking (p = .0496, exploratory). Averaged maximal carotid IMT progression (per year) was reduced by metformin versus placebo in never-smokers (-0.020 mm, 95% CI -0.034 to -0.006; p = .0067) but not in ever-smokers (-0.006 mm, 95% CI -0.020 to 0.008; p = .4067), although this analysis was not supported by a significant three-way interaction term. CONCLUSIONS: This subgroup analysis of the REMOVAL trial provides additional support for a potentially wider role of adjunct metformin therapy in cardiovascular risk management in type 1 diabetes, particularly for individuals who have never smoked cigarettes.


Assuntos
Diabetes Mellitus Tipo 1 , Metformina , Artérias Carótidas , Espessura Intima-Media Carotídea , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Método Duplo-Cego , Humanos , Metformina/uso terapêutico , Fatores de Risco , Fumantes , Fumar
17.
Nat Commun ; 12(1): 24, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402679

RESUMO

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.


Assuntos
Anorexia Nervosa/genética , Glicemia/metabolismo , Intolerância à Glucose/genética , Proteínas Substratos do Receptor de Insulina/genética , Resistência à Insulina/genética , Insulina/sangue , Fatores de Transcrição Kruppel-Like/genética , Adulto , Anorexia Nervosa/sangue , Anorexia Nervosa/etnologia , Anorexia Nervosa/fisiopatologia , Grupo com Ancestrais do Continente Europeu , Jejum/sangue , Feminino , Expressão Gênica , Loci Gênicos , Estudo de Associação Genômica Ampla , Intolerância à Glucose/sangue , Intolerância à Glucose/etnologia , Intolerância à Glucose/fisiopatologia , Humanos , Proteínas Substratos do Receptor de Insulina/sangue , Fatores de Transcrição Kruppel-Like/sangue , Masculino , Pessoa de Meia-Idade , Fenótipo , Caracteres Sexuais , Fatores Sexuais , Relação Cintura-Quadril
19.
J Infect Dis ; 223(2): 238-246, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-32909605

RESUMO

BACKGROUND: Whether latent cytomegalovirus (CMV) infection in older adults has any substantial health consequences is unclear. Here, we sought associations between CMV-seropositivity and IgG titer with all-cause and cardiovascular mortality in 5 longitudinal cohorts. METHODS: Leiden Longevity Study, Prospective Study of Pravastatin in the Elderly at Risk, Longitudinal Study of Aging Danish Twins, and Leiden 85-plus Study were assessed at median (2.8-11.4 years) follow-up . Cox regression and random effects meta-analysis were used to estimate mortality risk dependent on CMV serostatus and/or IgG antibody titer, in quartiles after adjusting for confounders. RESULTS: CMV-seropositivity was seen in 47%-79% of 10 122 white community-dwelling adults aged 59-93 years. Of these, 3519 had died on follow-up (579 from cardiovascular disease). CMV seropositivity was not associated with all-cause (hazard ratio [HR], 1.05; 95% confidence interval [CI], .97-1.14) or cardiovascular mortality (HR, 0.97; 95% CI, .83-1.13). Subjects in the highest CMV IgG quartile group had increased all-cause mortality relative to CMV-seronegatives (HR, 1.16; 95% CI, 1.04-1.29) but this association lost significance after adjustment for confounders (HR, 1.13; 95% CI, .99-1.29). The lack of increased mortality risk was confirmed in subanalyses. CONCLUSIONS: CMV infection is not associated with all-cause or cardiovascular mortality in white community-dwelling older adults.


Assuntos
Doenças Cardiovasculares/mortalidade , Infecções por Citomegalovirus/mortalidade , Citomegalovirus , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/imunologia , Doenças Cardiovasculares/epidemiologia , Causas de Morte , Estudos de Coortes , Comorbidade , Citomegalovirus/imunologia , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/imunologia , Feminino , Avaliação Geriátrica , Humanos , Imunoglobulina G/imunologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Vigilância em Saúde Pública , Estudos Soroepidemiológicos
20.
Eur Heart J Qual Care Clin Outcomes ; 7(3): 287-294, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31922541

RESUMO

AIMS: Risk estimation is important to motivate patients to adhere to treatment and to identify those in whom additional treatments may be warranted and expensive treatments might be most cost effective. Our aim was to develop a simple risk model based on readily available risk factors for patients with stable coronary artery disease (CAD). METHODS AND RESULTS: Models were developed in the CLARIFY registry of patients with stable CAD, first incorporating only simple clinical variables and then with the inclusion of assessments of left ventricular function, estimated glomerular filtration rate, and haemoglobin levels. The outcome of cardiovascular death over ∼5 years was analysed using a Cox proportional hazards model. Calibration of the models was assessed in an external study, the CORONOR registry of patients with stable coronary disease. We provide formulae for calculation of the risk score and simple integer points-based versions of the scores with associated look-up risk tables. Only the models based on simple clinical variables provided both good c-statistics (0.74 in CLARIFY and 0.80 or over in CORONOR), with no lack of calibration in the external dataset. CONCLUSION: Our preferred model based on 10 readily available variables [age, diabetes, smoking, heart failure (HF) symptom status and histories of atrial fibrillation or flutter, myocardial infarction, peripheral arterial disease, stroke, percutaneous coronary intervention, and hospitalization for HF] had good discriminatory power and fitted well in an external dataset. STUDY REGISTRATION: The CLARIFY registry is registered in the ISRCTN registry of clinical trials (ISRCTN43070564).

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