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AIMS: Few randomized trials assessed the changes over time in the chronotropic heart rate (HR) reactivity (CHR), HR recovery (HRR) and exercise endurance (EE) in response to the incremental shuttle walk test (ISWT). We addressed this issue by analysing the open HOMAGE (Heart OMics in Aging) trial. METHODS: In HOMAGE, 527 patients prone to heart failure were randomized to usual treatment with or without spironolactone (25-50 mg/day). The current sub-study included 113 controls and 114 patients assigned spironolactone (~70% on beta-blockers), who all completed the ISWT at baseline and at Months 1 and 9. Within-group changes over time (follow-up minus baseline) and between-group differences at each time point (spironolactone minus control) were analysed by repeated measures ANOVA, unadjusted or adjusted for sex, age and body mass index, and additionally for baseline for testing 1 and 9 month data. RESULTS: Irrespective of randomization, the resting HR and CHR did not change from baseline to follow-up, with the exception of a small decrease in the HR immediately post-exercise (-3.11 b.p.m.) in controls at Month 9. In within-group analyses, HR decline over the 5 min post-exercise followed a slightly lower course at the 1 month visit in controls and at the 9 month visits in both groups, but not at the 1 month visit in the spironolactone group. Compared with baseline, EE increased by two to three shuttles at Months 1 and 9 in the spironolactone group but remained unchanged in the control group. In the between-group analyses, irrespective of adjustment, there were no HR differences at any time point from rest up to 5 min post-exercise or in EE. Subgroup analyses by sex or categorized by the medians of age, left ventricular ejection fraction or glomerular filtration rate were confirmatory. Combining baseline and Months 1 and 9 data in both treatment groups, the resting HR, CHR and HRR at 1 and 5 min averaged 61.5, 20.0, 9.07 and 13.8 b.p.m. and EE 48.3 shuttles. CONCLUSIONS: Spironolactone on top of usual treatment compared with usual treatment alone did not change resting HR, CHR, HRR and EE in response to ISWT. Beta-blockade might have concealed the effects of spironolactone. The current findings demonstrate that the ISWT, already used in a wide variety of pathological conditions, is a practical instrument to measure symptom-limited exercise capacity in patients prone to developing heart failure because of coronary heart disease.
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Pulse pressure amplification (PPA) is the brachial-to-aortic pulse pressure ratio and decreases with age and cardiovascular risk factors. This individual-participant meta-analysis of population studies aimed to define an outcome-driven threshold for PPA. Incidence rates and standardized multivariable-adjusted hazard ratios (HRs) of cardiovascular and coronary endpoints associated with PPA, as assessed by the SphygmoCor software, were evaluated in the International Database of Central Arterial Properties for Risk Stratification (n = 5608). Model refinement was assessed by the integrated discrimination (IDI) and net reclassification (NRI) improvement. Age ranged from 30 to 96 years (median 53.6). Over 4.1 years (median), 255 and 109 participants experienced a cardiovascular or coronary endpoint. In a randomly defined discovery subset of 3945 individuals, the rounded risk-carrying PPA thresholds converged at 1.3. The HRs for cardiovascular and coronary endpoints contrasting PPA < 1.3 vs ≥1.3 were 1.54 (95% confidence interval [CI]: 1.00-2.36) and 2.45 (CI: 1.20-5.01), respectively. Models were well calibrated, findings were replicated in the remaining 1663 individuals analyzed as test dataset, and NRI was significant for both endpoints. The HRs associating cardiovascular and coronary endpoints per PPA threshold in individuals <60 vs ≥60 years were 3.86 vs 1.19 and 6.21 vs 1.77, respectively. The proportion of high-risk women (PPA < 1.3) was higher at younger age (<60 vs ≥60 years: 67.7% vs 61.5%; P < 0.001). In conclusion, over and beyond common risk factors, a brachial-to-central PP ratio of <1.3 is a forerunner of cardiovascular coronary complications and is an underestimated risk factor in women aged 30-60 years. Our study supports pulse wave analysis for risk stratification.
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Acute coronary syndrome (ACS) remains a major cause of morbidity and mortality, despite many improvements in its prevention and management. Lipid management is an important aspect of secondary prevention after ACS. Previous studies indicate that the early use of intensive statin therapy in patients with ACS may alleviate the risk of recurrent cardiovascular events and mortality. However, many patients do not reach the target low-density lipoprotein cholesterol (LDL-C) level of < 55 mg/dL with statin monotherapy, and muscle-related adverse effects caused by statins hinder adherence to treatment. Novel non-statin agents are recommended for patients who cannot achieve the target LDL-C levels with high-intensity statin therapy and those with statin intolerance. The combination of statins and non-statins may synergistically affect intensively lowering LDL-C through different mechanisms, which could lead to better cardiovascular outcomes than statin monotherapy. However, it remains uncertain whether the early use of combination lipid-lowering therapy is more beneficial. The present review summarizes the benefits of intensive statin monotherapy and their early combination with non-statin medications including ezetimibe, PCSK9 inhibitors, inclisiran, and bempedoic acid (BDA) in the management of ACS.
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INTRODUCTION: The prognostic values of estimated glomerular filtration rate (eGFR) calculated by different formulas have not been adequately compared in patients with heart failure with preserved ejection fraction (HFpEF). AIM: We compared the predictive values of serum creatinine-based eGFRs calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, Modification of Diet in Renal Disease Study (MDRD) formula, and full-age-spectrum creatinine (FAS Cr) equation in 1751 HFpEF patients. METHODS: The area under the receiver-operating characteristic curve (AUC), integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were employed. RESULTS: eGFR values were lowest calculated with FAS Cr equation (p < 0.001). When patients were classified into 4 subgroups (eGFR ≥ 90, 89-60, 59-30, and < 30 ml/min/1.73 m2) or only 2 subgroups (≥ 60 or < 60 ml/min/1.73 m2), the 3 formulas correlated significantly, with the best correlation found between the MDRD and CKD-EPI formulas (kappa = 0.871 and 0.963, respectively). The 3 formulas conveyed independent prognostic information. After adjusting for potential cofounders, risk prediction for all-cause mortality was more accurate (p = 0.001) using the CKD-EPI equation than MDRD formula as assessed by AUC. Compared with MDRD formula, CKD-EPI equation exhibited superior predictive ability assessed by IDI and NRI of 0.32% (p < 0.001)/10.4% (p = 0.010) for primary endpoint and 0.37% (p = 0.010)/10.8% (p = 0.010) for HF hospitalization. The risk prediction for deterioration of renal function was more accurate (p ≤ 0.040) using the CKD-EPI equation than FAS Cr equation as assessed by AUC, IDI, and NRI. CONCLUSION: The CKD-EPI formula might be the preferred creatinine-based equation in clinical risk stratification in HFpEF patients.
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Biomarcadores , Creatinina , Taxa de Filtração Glomerular , Insuficiência Cardíaca , Rim , Valor Preditivo dos Testes , Insuficiência Renal Crônica , Volume Sistólico , Função Ventricular Esquerda , Humanos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/sangue , Masculino , Feminino , Idoso , Creatinina/sangue , Pessoa de Meia-Idade , Prognóstico , Biomarcadores/sangue , Rim/fisiopatologia , Medição de Risco , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/sangue , Fatores de Risco , Idoso de 80 Anos ou mais , Reprodutibilidade dos Testes , Estudos Retrospectivos , Modelos BiológicosRESUMO
BACKGROUND: Wave separation analysis enables individualized evaluation of the aortic pulse wave components. Previous studies focused on the pressure height with overall positive but differing results. In the present analysis, we assessed the associations of the pressure of forward and backward (Pfor and Pref) pulse waves with prospective cardiovascular end points, with extended analysis for time to pressure peak (Tfor and Tref). METHODS: Participants in 3 IDCARS (International Database of Central Arterial Properties for Risk Stratification) cohorts (Argentina, Belgium, and Finland) aged ≥20 years with valid pulse wave analysis and follow-up data were included. Pulse wave analysis was done using the SphygmoCor device, and pulse wave separation was done using the triangular method. The primary end points consisted of cardiovascular mortality and nonfatal cardiovascular and cerebrovascular events. Multivariable-adjusted Cox regression was used to calculate hazard ratios. RESULTS: A total of 2206 participants (mean age, 57.0 years; 55.0% women) were analyzed. Mean±SDs for Pfor, Pref, Tfor, and Tfor/Tref were 31.0±9.1 mmâ Hg, 20.8±8.4 mmâ Hg, 130.8±35.5, and 0.51±0.11, respectively. Over a median follow-up of 4.4 years, 146 (6.6%) participants experienced a primary end point. Every 1 SD increment in Pfor, Tfor, and Tfor/Tref was associated with 27% (95% CI, 1.07-1.49), 25% (95% CI, 1.07-1.45), and 32% (95% CI, 1.12-1.56) higher risk, respectively. Adding Tfor and Tfor/Tref to existing risk models improved model prediction (∆Uno's C, 0.020; P<0.01). CONCLUSIONS: Pulse wave components were predictive of composite cardiovascular end points, with Tfor/Tref showing significant improvement in risk prediction. Pending further confirmation, the ratio of time to forward and backward pressure peak may be useful to evaluate increased afterload and signify increased cardiovascular risk.
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Doenças Cardiovasculares , Rigidez Vascular , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Prospectivos , Coração , Aorta , Frequência Cardíaca , Artérias , Análise de Onda de Pulso , Pressão Sanguínea , Fatores de RiscoRESUMO
The effects of long-term levels of body mass index (BMI), blood pressure (BP), plasma lipids and fasting blood glucose (FBG) on the cardiac structure and function in later life in general population are to evaluate. We included adult participants without heart failure from Framingham Heart Study. The respective averages over a span of 30-36 years of seven parameters were pooled into linear regression models simultaneously to evaluate their associations with subsequent left atrial internal dimension (LAID), left ventricular mass index (LVMi), internal dimension (LVID), ejection fraction (LVEF), global longitudinal strain (GLS) and mitral inflow velocity to early diastolic mitral annular velocity (E/é). In 1838 participants (56.0% female, mean age 66.1 years), per 1-standard deviation (SD) increment of mean BMI correlated with larger LAID and LVID (ß 0.05~0.17, standard error [SE] 0.01 for all), greater LVMi (ß [SE], 1.49 [0.46]), worse E/é (ß [SE], 0.28 [0.05]). Per 1-SD increment of mean systolic BP correlated with greater LVMi (ß [SE], 4.70 [0.69]), LVEF (ß [SE], 0.73 [0.24]), E/é (ß [SE], 0.52 [0.08]), whereas increase of mean diastolic BP correlated with smaller LVMi (ß [SE], -1.61 [0.62]), LVEF (ß [SE], -0.46 [0.22]), E/é (ß [SE], -0.30 [0.07]). Per 1-SD increment of mean high density lipoprotein cholesterol (HDL-c) correlated with smaller LVID (ß [SE], -0.03 [0.01]) and better systolic function (LVEF, ß [SE], 0.63 [0.19]; GLS, ß [SE], -0.20 [0.10]). The variabilities of BMI, BP and HDL-c also correlated with certain cardiac measurements. In long-term, BMI affected the size and mass of heart chambers, systolic and diastolic BP differently influenced left ventricular mass and function, higher HDL-c linked to better systolic function. Clinical trial registration: URL: https://clinicaltrials.gov . Identifier: NCT00005121.
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Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pressão Sanguínea , Estudos Longitudinais , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologiaRESUMO
BACKGROUND: It remains unclear whether systolic (SBP) and diastolic (DBP) pressure and BP response after six-minute walk test (6MWT) are associated with adverse outcomes in patients with acute heart failure (AHF). METHODS: We investigated these associations in 98 AHF patients (24.5% women; mean age, 70.5 years) enrolled in the ROSE trial (The Low-dose Dopamine or Low-dose Nesiritide in Acute Heart Failure with Renal Dysfunction). The primary endpoint consisted of any death or rehospitalization within 6 months after randomization. We computed hazard ratios (HRs) of the risks associated with 1-SD increase in post-exercise BP levels and BP ratios, calculated as BP immediately after 6MWT divided by BP before 6MWT. RESULTS: The BP before and after 6MWT averaged 110.6/117.5 mm Hg for SBP and 61.9/64.7 mm Hg for DBP. In multivariable-adjusted analyses including clinic BP measured at the same day of 6MWT, higher DBP after 6MWT was associated with lower risk of the primary endpoint (HR, 0.49; 95% confidence interval [CI], 0.26-0.95; Pâ =â 0.034). Both higher SBP and DBP immediately after 6MWT were associated with lower risk of 6-month mortality (HRs, 0.39/0.16; 95% CI, 0.17-0.90/0.065-0.40; Pâ ≤â 0.026). The post-exercise SBP ratio was associated with the risk of 6-month mortality in multivariable-adjusted analyses (HR, 0.44; Pâ =â 0.023). CONCLUSIONS: Higher BP levels and BP ratios immediately after 6MWT conferred lower risk of adverse health outcomes. Our observations highlight that 6MWT-related BP level and response may refine risk estimates in patients hospitalized AHF and may help further investigation for the development of HF preventive strategies.
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Insuficiência Cardíaca , Hipertensão , Humanos , Feminino , Idoso , Masculino , Pressão Sanguínea , Prognóstico , Teste de CaminhadaRESUMO
BACKGROUND: A recently developed urinary peptidomics biological aging clock can be used to study accelerated human aging. From 1990 to 2019, exposure to airborne particulate matter (PM) became the leading environmental risk factor worldwide. OBJECTIVES: This study investigated whether air pollution exposure is associated with accelerated urinary peptidomic aging, independent of calendar age, and whether this association is modified by other risk factors. METHODS: In a Flemish population, the urinary peptidomic profile (UPP) age (UPP-age) was derived from the urinary peptidomic profile measured by capillary electrophoresis coupled with mass spectrometry. UPP-age-R was calculated as the residual of the regression of UPP-age on chronological age, which reflects accelerated aging predicted by UPP-age, independent of chronological age. A high-resolution spatial-temporal interpolation method was used to assess each individual's exposure to PM10, PM2.5, black carbon (BC), and nitrogen dioxide (NO2). Associations of UPP-age-R with these pollutants were investigated by mixed models, accounting for clustering by residential address and confounders. Effect modifiers of the associations between UPP-age-R and air pollutants that included 18 factors reflecting vascular function, renal function, insulin resistance, lipid metabolism, or inflammation were evaluated. Direct and indirect (via UPP-age-R) effects of air pollution on mortality were evaluated by multivariable-adjusted Cox models. RESULTS: Among 660 participants (50.2% women; mean age: 50.7 y), higher exposure to PM10, PM2.5, BC, and NO2 was associated with a higher UPP-age-R. Studying effect modifiers showed that higher plasma levels of desphospho-uncarboxylated matrix Gla protein (dpucMGP), signifying poorer vitamin K status, steepened the slopes of UPP-age-R on the air pollutants. In further analyses among participants with dpucMGP ≥4.26µg/L (median), an interquartile range (IQR) higher level in PM10, PM2.5, BC, and NO2 was associated with a higher UPP-age-R of 2.03 [95% confidence interval (CI): 0.60, 3.46], 2.22 (95% CI: 0.71, 3.74), 2.00 (95% CI: 0.56, 3.43), and 2.09 (95% CI: 0.77, 3.41) y, respectively. UPP-age-R was an indirect mediator of the associations of mortality with the air pollutants [multivariable-adjusted hazard ratios from 1.094 (95% CI: 1.000, 1.196) to 1.110 (95% CI: 1.007, 1.224)] in participants with a high dpucMGP, whereas no direct associations were observed. DISCUSSION: Ambient air pollution was associated with accelerated urinary peptidomics aging, and high vitamin K status showed a potential protective effect in this population. Current guidelines are insufficient to decrease the adverse health effects of airborne pollutants, including healthy aging trajectories. https://doi.org/10.1289/EHP13414.
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Poluentes Atmosféricos , Poluição do Ar , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Prospectivos , Vitamina K/análise , Exposição Ambiental/análise , Poluição do Ar/análise , Poluentes Atmosféricos/análise , Material Particulado/análise , Envelhecimento , Dióxido de Nitrogênio/análise , Biomarcadores/análiseRESUMO
BACKGROUND AND AIMS: It remains unclear whether the long-term prognostic value of serum uric acid (SUA) at admission differs in acute decompensated heart failure (HF) patients across the spectrum of left ventricular ejection fraction (EF). METHODS AND RESULTS: In 2375 patients (38.9% women; mean age, 68.8 years), we assessed the risk of long-term (>1 year) all-cause mortality associated with per 1-SD increase in SUA at admission, using multivariable Cox regression in HF with preserved (HFpEF), mildly reduced (HFmrEF) and reduced (HFrEF) EF. During a median follow-up of 4.1 years, the long-term mortality rate was 39.9%. In all patients, the multivariable-adjusted hazard ratio (HR) expressing the risk of long-term mortality associated with SUA was 1.18 (95% CI, 1.11-1.26; P < 0.001). Compared with the low tertile of the SUA distribution, the sex- and age-adjusted cumulative incidence of long-term mortality was higher in the top tertile. In patients with HFpEF and HFrEF, SUA predicted the risk of long-term mortality with HRs amounting to 1.12 (95% CI, 1.02-1.21; P = 0.012) and 1.28 (95% CI, 1.12-1.47; P < 0.001), respectively. However, there were no associations between the risk of mortality and SUA in HFmrEF. Furthermore, age, sex, NYHA class, and the prevalence of coronary heart disease interacted significantly with SUA for predicting long-term mortality. CONCLUSION: Higher levels of SUA at admission were associated with higher risk of long-term mortality in patients with different HF subtypes. The risk conferred by SUA was age and sex dependent. Our observations highlight that measuring SUA at admission may help to improve risk stratification.
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Insuficiência Cardíaca , Humanos , Feminino , Idoso , Masculino , Insuficiência Cardíaca/epidemiologia , Ácido Úrico , Volume Sistólico , Função Ventricular Esquerda , Prognóstico , FenótipoRESUMO
BACKGROUND: Aortic pulse wave velocity (PWV) predicts cardiovascular events (CVEs) and total mortality (TM), but previous studies proposing actionable PWV thresholds have limited generalizability. This individual-participant meta-analysis is aimed at defining, testing calibration, and validating an outcome-driven threshold for PWV, using 2 populations studies, respectively, for derivation IDCARS (International Database of Central Arterial Properties for Risk Stratification) and replication MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease Health Survey - Copenhagen). METHODS: A risk-carrying PWV threshold for CVE and TM was defined by multivariable Cox regression, using stepwise increasing PWV thresholds and by determining the threshold yielding a 5-year risk equivalent with systolic blood pressure of 140 mm Hg. The predictive performance of the PWV threshold was assessed by computing the integrated discrimination improvement and the net reclassification improvement. RESULTS: In well-calibrated models in IDCARS, the risk-carrying PWV thresholds converged at 9 m/s (10 m/s considering the anatomic pulse wave travel distance). With full adjustments applied, the threshold predicted CVE (hazard ratio [CI]: 1.68 [1.15-2.45]) and TM (1.61 [1.01-2.55]) in IDCARS and in MONICA (1.40 [1.09-1.79] and 1.55 [1.23-1.95]). In IDCARS and MONICA, the predictive accuracy of the threshold for both end points was ≈0.75. Integrated discrimination improvement was significant for TM in IDCARS and for both TM and CVE in MONICA, whereas net reclassification improvement was not for any outcome. CONCLUSIONS: PWV integrates multiple risk factors into a single variable and might replace a large panel of traditional risk factors. Exceeding the outcome-driven PWV threshold should motivate clinicians to stringent management of risk factors, in particular hypertension, which over a person's lifetime causes stiffening of the elastic arteries as waypoint to CVE and death.
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Doenças Cardiovasculares , Hipertensão , Rigidez Vascular , Humanos , Análise de Onda de Pulso/efeitos adversos , Aorta , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/complicações , Artérias , Fatores de Risco , Rigidez Vascular/fisiologiaRESUMO
BACKGROUND: Epicardial adipose tissue (EAT) has been suggested to exert deleterious effects on myocardium and cardiovascular disease (CVD) consequence. We evaluated the associations of EAT thickness with adverse outcomes and its potential mediators in the community. METHODS: Participants without heart failure (HF) who had undergone cardiac magnetic resonance (CMR) to measure EAT thickness over the right ventricular free wall from the Framingham Heart Study were included. The correlation of EAT thickness with 85 circulating biomarkers and cardiometric parameters was assessed in linear regression models. The occurrence of HF, atrial fibrillation, coronary heart disease (CHD), and other adverse events was tracked since CMR was implemented. Their associations with EAT thickness and the mediators were evaluated using Cox regression and causal mediation analysis. RESULTS: Of 1554 participants, 53.0% were females. Mean age, body mass index, and EAT thickness were 63.3 years, 28.1 kg/m2, and 9.8 mm, respectively. After fully adjusting, EAT thickness positively correlated with CRP, LEP, GDF15, MMP8, MMP9, ORM1, ANGPTL3, and SERPINE1 and negatively correlated with N-terminal pro-B-type natriuretic peptide (NT-proBNP), IGFBP1, IGFBP2, AGER, CNTN1, and MCAM. Increasing EAT thickness was associated with smaller left ventricular end-diastolic dimension, thicker left ventricular wall thickness, and worse global longitudinal strain (GLS). During a median follow-up of 12.7 years, 101 incident HF occurred. Per 1-standard deviation increment of EAT thickness was associated with a higher risk of HF (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.19-1.72, P < 0.001) and the composite outcome consisting of myocardial infarction, ischemic stroke, HF, and death from CVD (adjusted HR [95% CI], 1.23 [1.07-1.40], P = 0.003). Mediation effect in the association between thicker EAT and higher risk of HF was observed with NT-proBNP (HR [95% CI], 0.95 [0.92-0.98], P = 0.011) and GLS (HR [95% CI], 1.04 [1.01-1.07], P = 0.032). CONCLUSIONS: EAT thickness was correlated with inflammation and fibrosis-related circulating biomarkers, cardiac concentric change, myocardial strain impairment, incident HF risk, and overall CVD risk. NT-proBNP and GLS might partially mediate the effect of thickened EAT on the risk of HF. EAT could refine the assessment of CVD risk and become a new therapeutic target of cardiometabolic diseases. TRIAL REGISTRATION: URL: https://clinicaltrials.gov . Identifier: NCT00005121.
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Doenças Cardiovasculares , Insuficiência Cardíaca , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/epidemiologia , Peptídeos Natriuréticos , Biomarcadores , Miocárdio , Tecido Adiposo/diagnóstico por imagem , Prognóstico , Volume Sistólico , Proteína 3 Semelhante a AngiopoietinaRESUMO
It remains unclear whether cumulative blood pressure (BP) exposure is associated with adverse outcomes in heart failure with preserved ejection fraction (HFpEF). The aim was to investigate the associations of adverse health outcomes with cumulative BP exposure as captured by weighted BP, cumulative BP and trends in BP over a 1-year timespan from baseline to a 12-month visit among 1303 patients with HFpEF (49.5% women; mean age, 71.5 years) enrolled in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial. The primary endpoints consisted of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure.We computed hazard ratios with a 1-SD increase in weighted BP and cumulative BP. In the spironolactone group, compared with patients with a downward trend in BP, those with an upward trend had higher event rates. However, there were no differences in event rates between those with upward and downward trends in BP in the placebo group. In multivariable-adjusted analyses that additionally accounted for baseline BP, weighted systolic BP and cumulative systolic BP predicted (P ≤ 0.037) the primary composite endpoint (hazard ratio [HR], 1.21; 95% CI, 1.05-1.39/1.15; 1.01-1.31) and hospitalization for HF (1.29; 1.09-1.52/1.18; 1.02-1.37), respectively. Among patients aged ≤72 years, cumulative systolic BP increased (P ≤ 0.016) the risk of the primary endpoint and hospitalization for HF. Higher cumulative systolic BP exposure conferred a higher risk of the primary endpoint and hospitalization for HF, independent of baseline BP. Our findings underscore that longitudinal BP measurements may refine risk stratification for patients with HFpEF.
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Insuficiência Cardíaca , Idoso , Feminino , Humanos , Masculino , Pressão Sanguínea , Insuficiência Cardíaca/tratamento farmacológico , Hospitalização , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Prognóstico , Espironolactona/uso terapêutico , Volume Sistólico/fisiologia , Resultado do TratamentoRESUMO
BACKGROUND: It remains unknown whether admission mean (MAP) and pulse pressure (PP) pressure are associated with short- and long-term mortality in Chinese patients with heart failure with preserved (HFpEF), mid-range (HFmrEF), and reduced (HFrEF) ejection fraction. METHODS: In 2,706 acute decompensated heart failure (HF) patients, we assessed the risk of 30-day, 1-year, and long-term (>1 year) mortality with 1-SD increment in MAP and PP, using multivariable logistic and Cox regression, respectively. RESULTS: During a median follow-up of 4.1 years, 1,341 patients died. The 30-day, 1-year, and long-term mortality were 3.5%, 16.7%, and 39.4%, respectively. A lower MAP was associated with a higher risk of 30-day mortality in women (P = 0.023) and a higher risk of 30-day and 1-year mortality in men (P ≤ 0.006), while higher PP predicted long-term mortality in men (P ≤ 0.014) with no relationship observed in women. In adjusted analyses additionally accounted for PP, 1-SD increment in MAP was associated with 30-day mortality in HFpEF (odds ratio [OR], 0.63; 95% CI, 0.43 to 0.92; P = 0.018), with 1-year mortality in HFmrEF (OR, 0.46; 95% CI, 0.32 to 0.66; P < 0.001) and HFrEF (OR, 0.54; 95% CI, 0.40 to 0.72; P < 0.001). In the adjusted model additionally accounted for MAP, 1-SD increment in PP was associated with long-term mortality in HFpEF (hazard ratio, 1.16; 95% CI, 1.05 to 1.28; P = 0.003). CONCLUSIONS: A lower MAP was associated with a higher risk of short-term mortality in all HF subtypes, while a higher PP predicted a higher risk of long-term mortality in men and in HFpEF. Our observations highlight the clinical importance of admission blood pressure for risk stratification in HF subtypes.
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Insuficiência Cardíaca , Humanos , Feminino , Prognóstico , Pressão Sanguínea , Volume Sistólico/fisiologia , Fenótipo , Sistema de RegistrosRESUMO
It remains unknown whether systolic (SBP) and diastolic (DBP) pressure on admission are associated with short- and long-term mortality in Chinese patients with heart failure with preserved (HFpEF), mildly reduced (HFmrEF), and reduced (HFrEF) ejection fraction. In 2706 HF patients (39.1% women; mean age, 68.8 years), we assessed the risk of 30-day, 1-year, and long-term (> 1 year) mortality with 1-SD increment in SBP and DBP, using multivariable logistic and Cox regression, respectively. During a median follow-up of 4.1 years, 1341 patients died. The 30-day, 1-year, and long-term mortality were 3.5%, 16.7%, and 39.4%, respectively. In multivariable-adjusted analyses additionally accounted for DBP or SBP, a higher SBP conferred a higher risk of long-term mortality (hazard ratio, 1.11; 95% CI, 1.02-1.22; p = .017) and a lower DBP was associated with a higher risk of all types of mortality (p ≤ .011) in all HF patients. Independent of potential confounders including DBP or SBP, in patients with HFpEF, higher SBP and lower DBP levels predicted a higher risk of long-term mortality with hazard ratios amounting to 1.16 (95% CI, 1.04-1.29; p = .007) and .89 (95% CI, .80-.99; p = .028), respectively. In patients with HFmrEF and HFrEF, irrespective of adjustments of potential confounders, DBP was associated with 1-year mortality with odds ratios ranging from .49 to .62 (p ≤ .006). In conclusion, lower DBP and higher SBP levels on admission were associated with a higher risk of different types of all-cause mortality in Chinese patients with different HF subtypes. Our observations highlight that admission BP may help to improve risk stratification.
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Insuficiência Cardíaca , Hipertensão , Humanos , Feminino , Idoso , Masculino , Pressão Sanguínea , População do Leste Asiático , Volume SistólicoRESUMO
Platelet Endothelial Aggregation Receptor 1 (PEAR1) modulates angiogenesis and platelet contact-induced activation, which play a role in the pathogenesis of colorectal cancer. We therefore tested the association of incident colorectal cancer and genetic and epigenetic variability in PEAR1 among 2532 randomly recruited participants enrolled in the family-based Flemish Study on Environment, Genes and Health Outcomes (51.2% women; mean age 44.8 years). All underwent genotyping of rs12566888 located in intron 1 of the PEAR1 gene; in 926 participants, methylation at 16 CpG sites in the PEAR1 promoter was also assessed. Over 18.1 years (median), 49 colorectal cancers occurred, all in different pedigrees. While accounting for clustering of risk factors within families and adjusting for sex, age, body mass index, the total-to-HDL cholesterol ratio, serum creatinine, plasma glucose, smoking and drinking, use of antiplatelet and nonsteroidal anti-inflammatory drug, the hazard ratio of colorectal cancer contrasting minor-allele (T) carriers vs. major-allele (GG) homozygotes was 2.17 (95% confidence interval, 1.18-3.99; P = 0.013). Bootstrapped analyses, from which we randomly excluded from two to nine cancer cases, provided confirmatory results. In participants with methylation data, we applied partial least square discriminant analysis (PLS-DA) and identified two methylation sites associated with higher colorectal cancer risk and two with lower risk. In-silico analysis suggested that methylation of the PEAR1 promoter at these four sites might affect binding of transcription factors p53, PAX5, and E2F-1, thereby modulating gene expression. In conclusion, our findings suggest that genetic and epigenetic variation in PEAR1 modulates the risk of colorectal cancer in white Flemish. To what extent, environmental factors as exemplified by our methylation data, interact with genetic predisposition and modulate penetrance of colorectal cancer risk is unknown.
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Neoplasias Colorretais , Receptores de Superfície Celular , Adulto , Estudos de Coortes , Neoplasias Colorretais/genética , Metilação de DNA , Epigênese Genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Receptores de Superfície Celular/metabolismoRESUMO
BACKGROUND: Whether cardiovascular risk is more tightly associated with central (cSBP) than brachial (bSBP) systolic pressure remains debated, because of their close correlation and uncertain thresholds to differentiate cSBP into normotension versus hypertension. METHODS: In a person-level meta-analysis of the International Database of Central Arterial Properties for Risk Stratification (n=5576; 54.1% women; mean age 54.2 years), outcome-driven thresholds for cSBP were determined and whether the cross-classification of cSBP and bSBP improved risk stratification was explored. cSBP was tonometrically estimated from the radial pulse wave using SphygmoCor software. RESULTS: Over 4.1 years (median), 255 composite cardiovascular end points occurred. In multivariable bootstrapped analyses, cSBP thresholds (in mm Hg) of 110.5 (95% CI, 109.1-111.8), 120.2 (119.4-121.0), 130.0 (129.6-130.3), and 149.5 (148.4-150.5) generated 5-year cardiovascular risks equivalent to the American College of Cardiology/American Heart Association bSBP thresholds of 120, 130, 140, and 160. Applying 120/130 mm Hg as cSBP/bSBP thresholds delineated concordant central and brachial normotension (43.1%) and hypertension (48.2%) versus isolated brachial hypertension (5.0%) and isolated central hypertension (3.7%). With concordant normotension as reference, the multivariable hazard ratios for the cardiovascular end point were 1.30 (95% CI, 0.58-2.94) for isolated brachial hypertension, 2.28 (1.21-4.30) for isolated central hypertension, and 2.02 (1.41-2.91) for concordant hypertension. The increased cardiovascular risk associated with isolated central and concordant hypertension was paralleled by cerebrovascular end points with hazard ratios of 3.71 (1.37-10.06) and 2.60 (1.35-5.00), respectively. CONCLUSIONS: Irrespective of the brachial blood pressure status, central hypertension increased cardiovascular and cerebrovascular risk indicating the importance of controlling central hypertension.
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Determinação da Pressão Arterial , Hipertensão , Pressão Sanguínea/fisiologia , Artéria Braquial , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Medição de RiscoRESUMO
AIMS: Recent trials evaluating the effect of aspirin in the primary prevention of cardiovascular disease showed little or no benefit. However, the role of aspirin on the risk of incident heart failure (HF) remains elusive. This study aimed to evaluate the role of aspirin use on HF incidence in primary and secondary prevention and whether aspirin use increases the risk of incident HF in patients at risk. METHODS AND RESULTS: Data from 30 827 patients at risk for HF enrolled in six observational studies were analysed [women 33.9%, mean age (±standard deviation) 66.8 ± 9.2 years]. Cardiovascular risk factors and aspirin use were recorded at baseline, and patients were followed up for the first incident of fatal or non-fatal HF. The association of incident HF with aspirin use was assessed using multivariable-adjusted proportional hazard regression, which accounted for study and cardiovascular risk factors. Over 5.3 years (median; 5th-95th percentile interval, 2.1-11.7 years), 1330 patients experienced HF. The fully adjusted hazard ratio (HR) associated with aspirin use was 1.26 [95% confidence interval (CI) 1.12-1.41; P ≤ 0.001]. Further, in a propensity-score-matched analysis, the HR was 1.26 (95% CI 1.10-1.44; P ≤ 0.001). In 22 690 patients (73.6%) without history of cardiovascular disease, the HR was 1.27 (95% CI 1.10-1.46; P = 0.001). CONCLUSIONS: In patients, at risk, aspirin use was associated with incident HF, independent of other risk factors. In the absence of conclusive trial evidence, our observations suggest that aspirins should be prescribed with caution in patients at risk of HF or having HF.
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Doenças Cardiovasculares , Insuficiência Cardíaca , Idoso , Aspirina/efeitos adversos , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Fatores de RiscoRESUMO
It remains debated whether pulse pressure is associated with left ventricular traits and adverse outcomes over and beyond mean arterial pressure (MAP) in patients with heart failure (HF) with preserved ejection fraction. We investigated these associations in 3428 patients with HF with preserved ejection fraction (51.5% women; mean age, 68.6 years) enrolled in the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist). We computed association sizes and hazards ratios with 1-SD increase in MAP and pulse pressure. In multivariable-adjusted analyses, association sizes (P≤0.039) for MAP were 0.016 cm and 0.014 cm for septal and posterior wall thickness, -0.15 for E/A ratio, -0.66 for E/e', and -0.64% for ejection fraction, independent of pulse pressure. With adjustment additionally applied for MAP, E/A ratio and longitudinal strain increased with higher pulse pressure with association sizes amounting to 0.067 (P=0.026) and 0.40% (P=0.023). In multivariable-adjusted analyses of both placebo and spironolactone groups, lower MAP and higher pulse pressure predicted the primary composite end point (P≤0.028) and hospitalized HF (P≤0.002), whereas MAP was also significantly associated with total mortality (P≤0.007). Sensitivity analyses stratified by sex, median age, and region generated confirmatory results with exception for the association of adverse outcomes with pulse pressure in patients with age ≥69 years. In conclusion, the clinical application of MAP and pulse pressure may refine risk estimates in patients with HF with preserved ejection fraction. This finding may help further investigation for the development of HF with preserved ejection fraction preventive strategies targeting pulsatility and blood pressure control.
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Pressão Sanguínea/fisiologia , Insuficiência Cardíaca/fisiopatologia , Volume Sistólico/fisiologia , Idoso , Ecocardiografia , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To address to what extent central hemodynamic measurements, improve risk stratification, and determine outcome-based diagnostic thresholds, we constructed the International Database of Central Arterial Properties for Risk Stratification (IDCARS), allowing a participant-level meta-analysis. The purpose of this article was to describe the characteristics of IDCARS participants and to highlight research perspectives. METHODS: Longitudinal or cross-sectional cohort studies with central blood pressure measured with the SphygmoCor devices and software were included. RESULTS: The database included 10,930 subjects (54.8% women; median age 46.0 years) from 13 studies in Europe, Africa, Asia, and South America. The prevalence of office hypertension was 4,446 (40.1%), of which 2,713 (61.0%) were treated, and of diabetes mellitus was 629 (5.8%). The peripheral and central systolic/diastolic blood pressure averaged 129.5/78.7 mm Hg and 118.2/79.7 mm Hg, respectively. Mean aortic pulse wave velocity was 7.3 m per seconds. Among 6,871 participants enrolled in 9 longitudinal studies, the median follow-up was 4.2 years (5th-95th percentile interval, 1.3-12.2 years). During 38,957 person-years of follow-up, 339 participants experienced a composite cardiovascular event and 212 died, 67 of cardiovascular disease. CONCLUSIONS: IDCARS will provide a unique opportunity to investigate hypotheses on central hemodynamic measurements that could not reliably be studied in individual studies. The results of these analyses might inform guidelines and be of help to clinicians involved in the management of patients with suspected or established hypertension.
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Doenças Cardiovasculares , Hipertensão , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise de Onda de PulsoRESUMO
From 1990 until 2017, global air-pollution related mortality increased by 40%. Few studies addressed the renal responses to ultrafine particulate [≤ 2.5 µm (PM2.5)], including black carbon (BC), which penetrate into the blood stream. In a Flemish population study, glomerular filtration estimated from serum creatinine (eGFR) and the urinary albumin-to-creatinine ratio were measured in 2005-2009 in 820 participants (women, 50.7%; age, 51.1 years) with follow-up of 523 after 4.7 years (median). Serum creatinine, eGFR, chronic kidney disease (eGFR < 60 mL/min/1.73 m2) and microalbuminuria (> 3.5/> 2.5 mg per mmol creatinine in women/men) were correlated in individual participants via their residential address with PM2.5 [median 13.1 (range 0.3-2.9) µg/m3] and BC [1.1 (0.3-18) µg/m3], using mixed models accounting for address clusters. Cross-sectional and longitudinally, no renal outcome was associated with PM2.5 or BC in models adjusted for sex and baseline or time varying covariables, including age, blood pressure, heart rate, body mass index, plasma glucose, the total-to-HDL serum cholesterol ratio, alcohol intake, smoking, physical activity, socioeconomic class, and antihypertensive treatment. The subject-level geocorrelations of eGFR change with to BC and PM2.5 were 0.13 and 0.02, respectively (P ≥ 0.68). In conclusion, in a population with moderate exposure, renal function was unrelated to ultrafine particulate.