Reduction In Risk Of All-cause Mortality Research Articles

Association between 4-dimension lifestyle pattern and 10-year mortality risk in Chinese individuals older than 65: a population-based cohort study.

While the impact of a 4-dimension lifestyle pattern (4DL) on older people’s mortality (aged ≥65 years) has been reported in high-income countries, few studies investigated the association between lifestyle pattern and disease-accompanied mortality, or examined the difference among different age or gender groups in low- and middle-income countries. We followed up 16,954 Chinese older participants from 2008 to 2018 and adopted the Cox proportional hazard model to evaluate the protective effect of 4DL. After adjustment for confounders, individuals with 3-4 4DL scores had a 38% reduction in all-cause mortality risk, and up to 36%, 42% and 41% reduced risk of mortality accompanied by hypertension, respiratory disease and dementia, respectively in contrast with those scored 0. Compared with octogenarians, nonagenarians, and centenarians, adhering to 3-4 4DL could further reduce the mortality risks in the younger elderly (aged 65-79 years). This study shows that among the elderly population in China, participants who adhered to 4DL had a lower all-cause mortality risk than those who did not. Additionally, hypertension, respiratory disease, or dementia accompanied mortality risk was also reduced significantly. The findings indicated that the positive effects of 4DL on longevity should be acknowledged in China’s older population, especially for the younger elderly.

Physical activity is associated with reduced risk of liver disease in the prospective UK Biobank cohort

Background & AimsPrevious studies have identified physical activity as an important lifestyle factor in the pathogenesis of chronic liver diseases (CLD). However, most studies were short in follow-up, and based on self-reported activity. Moreover, it is unknown whether physical activity affects the risk of liver disease development in the general population. Herein, we aimed to clarify the association between physical activity and CLD by examining the risk of liver disease and progression in relation to accelerometer-based physical activity in a large subset of prospectively recruited participants in the UK Biobank.MethodsWe analysed data from 96,688 participants that recorded their physical activity through the use of a wrist accelerometer. Relative risks for development of liver diseases were calculated using multivariable-adjusted Cox regression models. In a subgroup of participants without any previously diagnosed liver disease (n = 95,974), a total of 374 liver disease cases were diagnosed during follow-up (mean = 5.5 years).ResultsParticipants in the top compared with the bottom quartile of physical activity had a reduced risk of both overall CLD (hazard ratio [HR]: 0.41 [0.29–0.59]) and NAFLD (HR: 0.39 [0.21–0.70]). An activity increase of an additional 2,500 steps per day, was associated with a 38% reduction in CLD and a 47% reduction in NAFLD development, independent of adiposity. In the subgroup of participants with previously diagnosed liver disease (n = 714), participants in the top compared with the bottom quartile of physical activity had a striking 89% risk reduction in liver-related death (HR: 0.11 [0.02–0.86]), and 85% risk reduction in all-cause mortality (adjusted HR: 0.15 [0.05–0.44]). Walking an additional 2,500 steps per day was associated with 44% reduction in liver disease progression.ConclusionsGreater physical activity is associated with a dose-dependent reduction in liver disease, which appears to be independent of adiposity.Lay summaryIn this study, we aimed to clarify the association between accelerometer-measured physical activity and chronic liver disease by examining risk of overall and specific liver diseases and their progression in relation to accelerometer-based physical activity in 96,688 participants in the UK Biobank. Our results show a clear, dose-dependent protective association between accelerometer-measured physical activity and liver disease development and progression. The linkage of device-measured activity could therefore create a framework for using wearables for personalised prevention of liver diseases.

Randomized Blinded Placebo-Controlled Trials of Renal Sympathetic Denervation for Hypertension: A Meta-Analysis

BackgroundThe efficacy of renal denervation has been controversial, but the procedure has now undergone several placebo-controlled trials. New placebo-controlled trial data has recently emerged, with longer follow-up of one trial and the full report of another trial (which constitutes 27% of the total placebo-controlled trial data). We therefore sought to evaluate the effect of renal denervation on ambulatory and office blood pressures in patients with hypertension. MethodsWe systematically identified all blinded placebo-controlled randomized trials of catheter-based renal denervation for hypertension. The primary efficacy outcome was ambulatory systolic blood pressure change relative to placebo. A random-effects meta-analysis was performed. Results6 studies randomizing 1232 patients were eligible. 713 patients were randomized to renal denervation and 519 to placebo. Renal denervation significantly reduced ambulatory systolic blood pressure (−3.52 mmHg; 95% CI −4.94 to −2.09; p < 0.0001), ambulatory diastolic blood pressure (−1.93 mmHg; 95% CI −3.04 to −0.83, p = 0.0006), office systolic blood pressure size (−5.10 mmHg; 95% CI −7.31 to −2.90, p < 0.0001) and office diastolic pressure (effect size −3.11 mmHg; 95% CI −4.43 to −1.78, p < 0.0001). Adverse events were rare and not more common with denervation. ConclusionsThe totality of blinded, randomized placebo-controlled data shows that renal denervation is safe and provides genuine reduction in blood pressure for at least 6 months post-procedure. If this effect continues in the long term, renal denervation might provide a life-long 10% relative risk reduction in major adverse cardiac events and 7.5% relative risk reduction in all-cause mortality.

Statin use and mortality in atrial fibrillation: A systematic review and meta-analysis of 100,287 patients

Statins are effective for reducing cardiovascular disease in patients at risk or with cardiovascular disease. The benefit of statin therapy on adverse cardiovascular outcomes in patients with non-valvular atrial fibrillation (AF) is not clear. We performed a systematic review and meta-analysis of studies retrieved from MEDLINE via PubMed and Cochrane (CENTRAL) database of studies investigating the efficacy of statins in AF patients. The principal endpoint was all-cause mortality. Other endpoints were cardiovascular mortality, ischemic stroke, composite endpoints and any bleeding. We included 14 studies (2 post-hoc analysis of randomized clinical trials, 8 prospective and 4 retrospective) with 100,287 AF patients, of whom 23,228 were on statins. The pooled hazard ratio (HR) for all-cause mortality was 0.59 (95 % Confidence Interval [CI] 0.54−0.65). This association was consistent by aging, sex and prevalent cardiovascular or cerebrovascular disease. and the beneficial effect was evident already after 12 months of therapy. The absolute risk reduction for all-cause mortality in patients treated with statins was 10 % (95 % CI 9–10). The pooled HR for statins against cardiovascular mortality was 0.75 (95 % CI 0.58−0.96). No association was found with other secondary endpoints. Regarding bleeding events, the pooled HR for statin use was 0.60 (95 % CI 0.48−0.76). Our meta-analysis shows that in AF patients, statin therapy was associated with a reduction in all-cause and cardiovascular mortality are reduced by 41 % and 25 %, respectively. Randomized clinical trials in AF patients are necessary, as well as clarity on AF-specific LDL cholesterol targets.

Comparison of cost-effectiveness of implantable cardioverter defibrillator therapy in patients for primary prevention in Latin America: an analysis using the Improve SCA study

Objective The mortality benefit of implantable cardioverter defibrillators (ICDs) for primary prevention (PP) of sudden cardiac arrest (SCA) has been well-established, but ICD therapy remains globally underutilized. The results of the Improve SCA study showed a 49% relative risk reduction in all-cause mortality among ICD patients with 1.5 primary prevention (1.5PP) characteristics (patients with one or more risk factors, p < 0.0001). We evaluated the cost-effectiveness of ICD compared to no ICD therapy among patients with 1.5PP characteristics in three Latin American countries and analyzed the factors involved in cost-effectiveness. Methods We used a published Markov model that compares costs and outcomes of ICD to no ICD therapy from local payers’ perspective and included country-specific and disease-specific inputs from the Improve SCA study and current literature. We used WHO-recommended willingness-to-pay (WTP) thresholds to assess cost-effectiveness and compared model outcomes between countries. Results Incremental costs per QALY (quality-adjusted life year) saved by ICD compared to no ICD therapy are Colombian Pesos COP$46,729,026 in Colombia, Mexican Pesos MXN$246,016 in Mexico, and Uruguayan Pesos UYU$1,213,614 in Uruguay in the base case scenario; all three figures are between 1–3-times GDP per capita for each country. One-way and probabilistic sensitivity analyses confirm the base case scenario results. Non-cardiac accumulated deaths are lower in Mexico, resulting in a comparatively increased cost-effective ICD therapy. Limitations The Improve SCA study was not randomized, so clinical results could be biased; however, measures were taken to reduce this bias. Costs and benefits were modelled beyond the timeline of direct observation in the Improve SCA study. Conclusions ICD therapy is cost-effective in Mexico and Uruguay and potentially cost-effective in Colombia for a 1.5PP population. Variability in ICER estimates by country can be explained by differences in non-cardiac deaths and cost inputs.

1462. The protective effect of pneumococcal vaccination on cardiovascular disease in adults: A systematic review and meta-analysis

BackgroundEpidemiological studies suggest a link between pneumococcal infection and an adverse cardiovascular outcome such as myocardial infarction. Therefore, studies have evaluated the protective effect of the 23-valent polysaccharide pneumococcal vaccination (PPV23), but results have varied. We conducted a meta-analysis to summarize the available evidence on the impact of PPV23 on cardiovascular diseaseMethodsA literature search from January 1946 to September 2019 was conducted in Embase, Medline and Cochrane. All studies evaluating PPV23 compared to a control (placebo, no vaccine or another vaccine) for any cardiovascular events including myocardial infarction (MI), heart failure, cerebrovascular events were included. Risk ratios (RRs) were pooled using random effects models.ResultsEighteen studies were included, with a total of 716,108 participants. Vaccination with PPV23 was associated with decreased risk of any cardiovascular event (RR: 0.91;95% CI: 0.84-0.99), and MI (RR of 0.88; 95% CI:0.79-0.98) in all age groups, with a significant effect in those 65 years and older, but not in the younger age group. Similarly, PPV23 vaccine was associated with significant risk reduction in all-cause mortality in all ages (RR: 0.78; 95%CI: 0.68-0.88), specifically in those aged 65 years and older (RR: 0.71; 95%CI: 0.60-0.84). A significant risk reduction in cerebrovascular disease was not observed following pneumococcal vaccination.ConclusionPolysaccharide pneumococcal vaccination decreases the risk of a cardiovascular event, specifically acute MI in the vaccinated population, particularly those 65 years of age and older. It would be highly beneficial to vaccinate the population who is at greater risk for cardiovascular diseases.DisclosuresFawziah Marra, BSc (Pharm), PharmD, Pfizer Inc (Research Grant or Support) Nirma Khatri Vadlamudi, BA, BS, MPH, Pfizer Inc (Research Grant or Support)

Selenium, antioxidants, cardiovascular disease, and all-cause mortality: a systematic review and meta-analysis of randomized controlled trials

ABSTRACTBackgroundAntioxidants have been promoted for cardiovascular disease (CVD) risk reduction and for the prevention of cancer. Our preliminary analysis suggested that only when selenium was present were antioxidant mixtures associated with reduced all-cause mortality.ObjectiveWe conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the effect of selenium supplementation alone and of antioxidant mixtures with or without selenium on the risk of CVD, cancer, and mortality.MethodsWe identified studies using the Cochrane Library, Medline, and Embase for potential CVD outcomes, cancer, and all-cause mortality following selenium supplementation alone or after antioxidant supplement mixtures with and without selenium up to June 5, 2020. RCTs of ≥24 wk were included and data were analyzed using random-effects models and classified by the Grading of Recommendations, Assessment, Development, and Evaluation approach.ResultsThe meta-analysis identified 9423 studies, of which 43 were used in the final analysis. Overall, no association of selenium alone or antioxidants was seen with CVD and all-cause mortality. However, a decreased risk with antioxidant mixtures was seen for CVD mortality when selenium was part of the mix (RR: 0.77; 95% CI: 0.62, 0.97; P = 0.02), with no association when selenium was absent. Similarly, when selenium was part of the antioxidant mixture, a decreased risk was seen for all-cause mortality (RR: 0.90; 95% CI: 0.82, 0.98; P = 0.02) as opposed to an increased risk when selenium was absent (RR: 1.09; 95% CI: 1.04, 1.13; P = 0.0002).ConclusionThe addition of selenium should be considered for supplements containing antioxidant mixtures if they are to be associated with CVD and all-cause mortality risk reduction. This trial was registered at https://www.crd.york.ac.uk/PROSPERO/ as CRD42019138268.

Factors Associated With Failure to Achieve the Intensive Blood Pressure Target in the Systolic Blood Pressure Intervention Trial (SPRINT).

SPRINT (Systolic Blood Pressure Intervention Trial) found that randomization of nondiabetic participants at high cardiovascular risk to an intensive (systolic blood pressure [SBP] <120 mm Hg) versus standard (SBP <140 mm Hg) target resulted in 25% risk reduction in the first cardiovascular composite event (ie, cardiovascular death or nonfatal myocardial infarction, stroke, or hospitalization for heart failure) and a 27% risk reduction in all-cause mortality. In this post hoc analysis, we sought to determine the factors associated with failure to achieve the SBP target in 4678 SPRINT participants randomized to the intensive treatment group. Using a generalized estimating equation model, we assessed variables associated with failure to achieve the intensive SBP target as a repeated outcome collected during serial follow-up visits, including the occurrence of serious adverse events. In the multivariable model adjusted for baseline demographic, clinical, and laboratory variables, older age, higher SBP, underlying chronic kidney disease, higher number of antihypertensives, and moderate cognitive impairment at screening were associated with failure to achieve the intensive SBP target. Occurrence of a serious adverse event during the trial was associated with 20% higher odds of failure to achieve the SBP target. Participants of Hispanic ethnicity had 47% lower odds of failure to achieve the intensive SBP target relative to non-Hispanic Whites. Understanding barriers to achieving intensive SBP targets should allow clinicians to optimize management of hypertension in patients at high risk for cardiovascular disease.

Endoscopic repair of atrial functional mitral regurgitation in heart failure: long-term effects

Abstract Introduction In patients with heart failure and preserved ejection fraction (HFpEF), even mild atrial functional mitral regurgitation (AFMR) has been associated with poor outcome. Objective To describe long-term effects of endoscopic mitral valve (MV) repair on outcome in patients with HFpEF and AFMR. Methods The study population consisted of consecutive patients with HFpEF (LVEF ≥50%, H2FPEF score ≥5) and AFMR, who underwent isolated, minimally invasive (endoscopic), MV repair (MVRepair group) (n=131) or remained on standard of care (StanCare group) (n=139). Patients with coronary artery disease or organic MR were excluded. Patients were matched using inverse probability of treatment weighting. Primary objective was all-cause mortality or HFpEF readmissions. Results The median follow up was 5.03 years (IQR 2.6–7.9 years). In the MVRepair group, the perioperative, 30-day, 1- and 5-year mortality was 0, 1% and 12%, respectively. Additional 13 (10%) patients were readmitted for worsening HFpEF, while 2 (1%) individuals underwent redo MV surgery for recurrent MR. MVRepair compared with StanCare showed 21–29% (SE 6–8%) and 19–26% (SE 6–8%) absolute risk reduction of all-cause mortality and HFpEF readmissions, respectively (all p&amp;lt;0.05). MVRepair emerged as the strongest independent predictor of all-cause mortality (HR 0.16, 95% CI 0.07–0.34, p&amp;lt;0.001) and HFpEF readmissions (HR 0.21, 95% CI 0.09–0.51, p&amp;lt;0.001). At 5-year follow-up, in the MVRepair group, a total of 88% were alive and 80% were alive without readmission for HFpEF. Conclusions Endoscopic MV repair is associated with low perioperative mortality, high long-term efficacy and appears to improve clinical outcome in patients with AFMR and HFpEF. Mortality and readmission for HF Funding Acknowledgement Type of funding source: None

Mitral Valve Repair of Atrial Functional Mitral Regurgitation in Heart Failure with Preserved Ejection Fraction.

Our objective was to describe the long-term effects of endoscopic mitral valve (MV) repair on outcome in patients with heart failure with preserved ejection fraction (HFpEF) and atrial functional mitral regurgitation (AFMR). In patients with HFpEF, even mild AFMR has been associated with poor outcome. The study population consisted of consecutive patients with HFpEF (left ventricular ejection fraction (LVEF) ≥ 50%, H2FPEF score ≥ 5) and AFMR, who underwent isolated, minimally invasive endoscopic MV repair (MVRepair group) (n = 131) or remained on standard of care (StanCare group) (n = 139). Patients with coronary artery disease or organic mitral regurgitation (MR) were excluded. Patients were matched using inverse probability of treatment weighting. Endpoints were all-cause mortality and a composite of all-cause mortality and HFpEF readmissions. The median follow-up was 5.03 years (interquartile range (IQR) 2.6–7.9 years). In the MVRepair group, the perioperative, 30-day, 1-year, and 5-year mortality were 0, 1%, 1%, and 12%, respectively. Additionally, 13 (10%) patients were readmitted for worsening HFpEF, while 2 (1%) individuals underwent redo MV surgery for recurrent MR. MVRepair compared with StanCare showed 21–29% (Standard Error (SE) 6–8%) and 19–26% (SE 6–8%) absolute risk reduction of all-cause mortality and HFpEF readmissions, respectively (all p < 0.05). MVRepair emerged as the strongest independent predictor of all-cause mortality (Hazard Ratio (HR) 0.16, 95% (Confidence Interval (CI) 0.07–0.34, p < 0.001) and HFpEF readmissions (HR 0.21, 95% CI 0.09–0.51, p < 0.001). At 5-year follow-up, in the MVRepair group, a total of 88% were alive and 80% were alive without readmission for HFpEF. We can conclude that endoscopic MV repair is associated with low perioperative mortality as well as high long-term efficacy, and appears to improve clinical outcome in patients with AFMR and HFpEF.

Lateral left ventricular lead position is superior to posterior position in long-term outcome of patients who underwent cardiac resynchronization therapy.

AimsPreferring side branch of coronary sinus during cardiac resynchronization therapy (CRT) implantation has been empirical due to the limited data on the association of left ventricular (LV) lead position and long‐term clinical outcome. We evaluated the long‐term all‐cause mortality by LV lead non‐apical positions and further characterized them by interlead electrical delay (IED).Methods and resultsIn our retrospective database, 2087 patients who underwent CRT implantation were registered between 2000 and 2018. Those with non‐apical LV lead locations were classified into anterior (n = 108), posterior (n = 643), and lateral (n = 1336) groups. All‐cause mortality was assessed by Kaplan–Meier and Cox analyses. Echocardiographic response was measured 6 months after CRT implantation. During the median follow‐up time of 3.7 years, 1150 (55.1%) patients died—710 (53.1%) with lateral, 78 (72.2%) with anterior, and 362 (56.3%) with posterior positions. When we investigated the risk of all‐cause mortality, there was a significantly lower rate of death in patients with lateral LV lead location when compared with those with an anterior (P < 0.01) or posterior (P < 0.01) position. Multivariate analysis after adjustment for relevant clinical covariates such as age, sex, ischaemic aetiology, left bundle branch block morphology, atrial fibrillation, and device type revealed consistent results that lateral position is associated with a significant risk reduction of all‐cause mortality when compared with anterior [hazard ratio 0.69; 95% confidence interval (CI) 0.55–0.87; P < 0.01] or posterior (hazard ratio 0.84; 95% CI 0.74–0.96; P < 0.01) position. When echocardiographic response was evaluated within the lateral group, patients with an IED longer than 110 ms (area under the receiver operating characteristic curve, 0.63; 95% CI 0.53–0.73; P = 0.012) showed 2.1 times higher odds of improvement in echocardiographic response 6 months after the implantation.ConclusionsIn this study, we proved in a real‐world patient population that after CRT implantation, lateral LV lead location was associated with long‐term mortality benefit and is superior to both anterior and posterior positions. Moreover, patients with this position showed the greatest echocardiographic response over 110 ms IED.

Re: Association of Inpatient Use of Angiotensin-converting Enzyme Inhibitors and Angiotensin II Receptor Blockers with Mortality Among Patients with Hypertension Hospitalized with COVID-19.

To the Editor: We read with interest the study by Zhang et al.,1 examining the association between inpatient use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) and mortality in patients hospitalized with coronavirus disease 2019 (COVID-19), published in Circulation Research. The use of ACEIs or ARBs was associated with an important 58% risk reduction in all-cause mortality (hazard ratio, 0.42; 95% confidence interval, 0.19, 0.92). The association was even stronger with the use of propensity score models, resulting in a risk reduction of almost 70%. We believe that these remarkable effects are mainly driven by immortal time bias. In this study, patients were deemed exposed to ACEIs or ARBs if they had received a prescription at any time during the hospitalization period. In contrast, patients who did not receive these drugs during the hospitalization period were categorized as nonusers. This method of identifying users and nonusers can introduce immortal time bias.2 Indeed, by design, ACEI or ARB users had to survive from the date of admission to the date of an ACEI or ARB prescription to be categorized as a user. This time period was both misclassified as exposed (instead of unexposed) and immortal, as it was impossible for patients to die during this time span. In contrast, it was possible for nonusers to die at any point during the hospitalization period. This is particularly evident in Zhang et al.’s1 Figures 2A and 2B, where there were no deaths in the first 7 days of follow-up for the ACEIs/ARBs group, whereas deaths occurred as early as the second day after admission in the non-user group. Given the maximum 28-day follow-up, even a small amount of misclassified exposed person–time could lead to important bias, as was shown previously with β-blockers for patients hospitalized for chronic obstructive pulmonary disease.3 The authors also compared the risk of death among users of ACEIs/ARBs versus users of other antihypertensive drugs. In this analysis, the authors first identified ACEI/ARB users and then users of other antihypertensive drugs. This hierarchical exposure definition introduced immortal time bias,4 as the time between hospital admission and first ACEI/ARB prescription was misclassified as exposed and immortal because no events could have occurred during that period. In summary, although residual confounding is always a concern in observational studies, immortal time bias can introduce severely skewed results, though it can be avoided using proper methods of analysis.2–4 It would be informative to repeat the analyses by modeling ACEI or ARB exposure using time-dependent methods.

The protective effect of pneumococcal vaccination on cardiovascular disease in adults: A systematic review and meta-analysis

BackgroundEpidemiological studies suggest that there is a link between pneumococcal infection and adverse cardiovascular outcomes such as myocardial infarction. Multiple studies have evaluated the protective effect of the 23-valent polysaccharide pneumococcal vaccination (PPV23), but results have varied. Therefore, a meta-analysis was conducted to summarize available evidence on the impact of PPV23 on cardiovascular disease. MethodsA literature search from January 1946 to September 2019 was conducted across Embase, Medline and Cochrane. All studies were included that evaluated PPV23 compared with a control (placebo, no vaccine or another vaccine) for any cardiovascular events, including: myocardial infarction (MI), heart failure and cerebrovascular events. Risk ratios (RRs) were pooled using random effects models. ResultsEighteen studies were included, with a total of 716,108 participants. Vaccination with PPV23 was associated with decreased risk of any cardiovascular event (RR: 0.91; 95% CI: 0.84−0.99), and MI (RR: 0.88; 95% CI: 0.79−0.98) in all age groups, with a significant effect in those aged ≥65 years, but not in the younger age group. Similarly, PPV23 vaccine was associated with significant risk reduction in all-cause mortality in all ages (RR: 0.78; 95% CI: 0.68−0.88), specifically in those aged ≥65 years (RR: 0.71; 95% CI: 0.60−0.84). A significant risk reduction in cerebrovascular disease was not observed following pneumococcal vaccination. ConclusionsPolysaccharide pneumococcal vaccination decreased the risk for some adverse cardiovascular events, specifically acute MI in the vaccinated population, particularly for those individuals aged ≥65 years. It would be highly beneficial to vaccinate the population who is at greater risk of cardiovascular diseases.

Association of Cardiac Rehabilitation With All-Cause Mortality Among Patients With Cardiovascular Disease in the Netherlands

Cardiac rehabilitation (CR) is an effective strategy to improve clinical outcomes, but it remains underused in some subgroups of patients with cardiovascular disease (CVD). To investigate the implications of sex, age, socioeconomic status, CVD diagnosis, cardiothoracic surgery, and comorbidity for the association between CR participation and all-cause mortality. Observational cohort study with patient enrollment between July 1, 2012, and December 31, 2017, and a follow-up to March 19, 2020. The dates of analysis were March to May 2020. This study was performed among Dutch patients with CVD with a multidisciplinary outpatient CR program indication and who were insured at Coöperatie Volksgezondheidszorg, one of the largest health insurance companies in the Netherlands. Among 4.1 million beneficiaries, patients with CVD with an acute coronary event (myocardial infarction or unstable angina pectoris), stable angina pectoris, chronic heart failure, or cardiothoracic surgery (coronary artery bypass grafting, valve replacement, or percutaneous coronary intervention) were identified by inpatient diagnosis codes and included in the study. Cox proportional hazards models were used to evaluate the association between CR participation and all-cause mortality. Stabilized inverse propensity score weighting was used to account for patient and disease characteristics associated with CR participation. Among 83 687 eligible patients with CVD (mean [SD] age, 67 [12] years; 60.4% [n = 50 512] men), only 31.3% (n = 26 171) participated in CR, with large variation across different subgroups (range, 5.1%-73.0%). During a mean (SD) of 4.7 (1.8) years of follow-up, 1966 CR participants (7.5%) and 13 443 CR nonparticipants (23.4%) died. After multivariable adjustment, CR participation was associated with a 32% lower risk of all-cause mortality (adjusted hazard ratio, 0.68; 95% CI, 0.65-0.71) compared with nonparticipation. Sex, age, socioeconomic status, and comorbidity did not alter risk reduction after CR participation, but a statistically significant interaction association was found across categories of CVD diagnosis and cardiothoracic surgery. Larger reductions in risk estimates for all-cause mortality were found after CR participation for STEMI (adjusted HR, 0.59; 95% CI, 0.52-0.68 vs 0.72; 95% CI, 0.65-0.79; P < .001), NSTEMI (adjusted HR, 0.64; 95% CI, 0.58-0.70 vs 0.72; 95% CI, 0.65-0.79; P < .001), and stable AP (adjusted HR, 0.69; 95% CI, 0.63-0.76 vs 0.72; 95% CI, 0.65-0.79; P < .001) compared with patients with chronic heart failure, whereas unstable AP had a smaller risk reduction (adjusted HR, 0.75; 95% CI, 0.67-0.85 vs 0.72; 95% CI, 0.65-0.79; P < .001). In this cohort study, CR participation was associated with a 32% risk reduction in all-cause mortality, and this benefit was independent of sex, age, socioeconomic status, and comorbidity. These findings reinforce the importance of CR participation in secondary prevention and highlight the possibility that CR should be prescribed more widely to vulnerable patients with CVD, such as older adults with chronic diseases or multimorbidity.

Análisis de la relación dosis-respuesta de la actividad física recreativa con los eventos cardiovasculares y la mortalidad por todas las causas: el estudio REGICOR

Introduction and objectivesRegular leisure-time physical activity (LTPA) has been consistently recognized as a protective factor for cardiovascular diseases (CVD) and all-cause mortality. However, the pattern of this relationship is still not clear. The aim of this study was to assess the relationship of LTPA with incident CVD and mortality in a Spanish population. MethodsA prospective population-based cohort of 11 158 randomly selected inhabitants from the general population. LTPA was assessed by a validated questionnaire. Mortality and CVD outcomes were registered during the follow-up (median: 7.24 years). The association between LTPA and outcomes of interest (all-cause mortality and cardiovascular disease) was explored using a generalized additive model with penalized smoothing splines and multivariate Cox proportional hazard models. ResultsWe observed a significant nonlinear association between LTPA and all-cause and CVD mortality, and fatal and nonfatal CVD. Moderate-vigorous intensity LTPA, but not light-intensity LTPA, were associated with beneficial effects. The smoothing splines identified a cutoff at 400 MET-min/d. Below this threshold, each increase of 100 MET-min/d in moderate-vigorous LTPA contributed with a 16% risk reduction in all-cause mortality (HR, 0.84; 95%CI, 0.77-0.91), a 27% risk reduction in CVD mortality (HR, 0.73; 95%CI, 0.61-0.87), and a 12% risk reduction in incident CVD (HR, 0.88; 95%CI, 0.79-0.99). No further benefits were observed beyond 400 MET-min/d. ConclusionsOur results support a nonlinear inverse relationship between moderate-vigorous LTPA and CVD and mortality. Benefits of PA are already observed with low levels of activity, with a maximum benefit around 3 to 5 times the current recommendations.Full English text available from:www.revespcardiol.org/en

Step By Step: Association Of Device-measured Daily Steps With All-cause Mortality - A Prospective Cohort Study

Walking - a basic unit of locomotion - is free, does not require special training, and can be done almost everywhere. Therefore, walking might be a feasible behavior on which to tailor public health messages. There is however insufficient evidence available to determine the magnitude and shape of the relationship between steps taken per day and all-cause mortality, giving current step-based guidelines limited scientific basis. PURPOSE: To assess the prospective association and dose-response relationship between device-measured daily walking steps and all-cause mortality in a large population-based cohort of women and men aged 40-85 years. METHODS: Daily steps were measured by a waist-mounted accelerometer in 2,180 individuals (53% women) for seven consecutive days at baseline (2008-09). Participants were grouped into quarters (Q) based on their average number of steps per day and followed over a median period of 9.1 years for all-cause mortality determined by linkage with death certificates from the Norwegian Cause of Death Registry. RESULTS: Mean (SD) baseline age was 56 (11) years. Median (IQR) steps per day were 4651 (3495, 5325), 6862 (6388, 7350), 8670 (8215, 9186), and 11467 (10556, 13110) in Q1 to Q4, respectively. During follow-up, 119 individuals died (68% men). Higher number of steps per day was associated with lower risk of all-cause mortality with hazard ratios (95% CI) of 0.52 (0.29 to 0.93), 0.50 (0.27 to 0.94), and 0.43 (0.21 to 0.88) across ascending quarters of steps per day compared with Q1 (referent) in the multivariable model (p<0.001). The dose-response association modelled using restricted cubic splines demonstrated a non-linear, inverse association between daily steps taken and all-cause mortality, with no apparent plateauing of risk-reduction within the observed variation in the exposure. CONCLUSIONS:We observed a 48% risk reduction for all-cause mortality between the least active and the second quartile, with an absolute difference between Q1 and Q2 of 2200 steps per day. To exemplify, given an average stride length of 0.67 cm for women and 0.76 cm for men, 2200 steps translates to a 1.4 to 1.6 km walk for women and men, respectively. If confirmed, this large gain with modest effort may serve as encouragement to many sedentary individuals.

The Independent And Combined Effects Of Aerobic Physical Activity And Muscular Strengthening Activity On All-Cause Mortality: An Analysis Of Effect Modification By Race-Ethnicity

The relationship between aerobic physical activity (PA) and all-cause mortality risk is well documented. However, the combined effects of sufficient aerobic PA and muscular strengthening activity (MSA) on all-cause mortality risk need further exploration. Moreover, the 2018 PA guidelines committee report suggests that effects of race-ethnicity on this relationship need to be examined. PURPOSE: To examine the independent and joint relationship between meeting the current aerobic PA and MSA recommendations and all-cause mortality while considering potential effect modification by race-ethnicity. METHODS: This study sample (n=14,384), included adults (20-79 years of age), who participated in the 1999-2006 NHANES. Participants self-reported participation in aerobic PA (leisure-time, transportation, household) and MSA. PA was categorized into 6 categories based around the 2018 PA guidelines: category 1 (no aerobic PA and no MSA), category 2 (insufficiently active and no MSA), category 3 (active and no MSA), category 4 (no PA and meeting the MSA recommendations), category 5 (insufficiently active and meeting the MSA recommendations), and category 6 (meeting both the aerobic and MSA recommendations). All-cause mortality was the dependent variable. Race-ethnic groups examined included non-Hispanic White (NHW), non-Hispanic Black (NHB) and Mexican American (MA). Cox-proportional hazard models were used for the total sample and for individual race-ethnicity estimates. RESULTS: A significant interaction was found between aerobic PA and race-ethnicity (p=0.0001) and MSA and race-ethnicity (p=0.0005). Significant risk reductions were found for categories 2,3 and 6 among NHW (cat 2: HR 0.76, 95% CI 0.64-0.91; cat 3: HR 0.63, 95% CI 0.52-0.74; cat 6: HR 0.58, 95% CI 0.44-0.76) and NHB (cat 2: HR 0.63, 95% CI 0.52-0.74; cat 3: HR 0.51, 95% CI 0.41-0.65; cat 6: HR 0.54, 95% CI 0.38-0.77). Among MA, only those meeting both guidelines had significant reductions in all-cause mortality risk (HR 0.54, 95% CI 0.32-0.92). CONCLUSIONS: In support of the most recent PA guidelines, participation in sufficient volumes of both aerobic PA and MSA lead to significant reductions in risk for all-cause mortality across race-ethnic groups. The positive effects of aerobic PA alone seem to be isolated to NHW and NHB.

Analysis of the dose-response relationship of leisure-time physical activity to cardiovascular disease and all-cause mortality: the REGICOR study

Introduction and objectivesRegular leisure-time physical activity (LTPA) has been consistently recognized as a protective factor for cardiovascular diseases (CVD) and all-cause mortality. However, the pattern of this relationship is still not clear. The aim of this study was to assess the relationship of LTPA with incident CVD and mortality in a Spanish population. MethodsA prospective population-based cohort of 11 158 randomly selected inhabitants from the general population. LTPA was assessed by a validated questionnaire. Mortality and CVD outcomes were registered during the follow-up (median: 7.24 years). The association between LTPA and outcomes of interest (all-cause mortality and cardiovascular disease) was explored using a generalized additive model with penalized smoothing splines and multivariate Cox proportional hazard models. ResultsWe observed a significant nonlinear association between LTPA and all-cause and CVD mortality, and fatal and nonfatal CVD. Moderate-vigorous intensity LTPA, but not light-intensity LTPA, were associated with beneficial effects. The smoothing splines identified a cutoff at 400 MET-min/d. Below this threshold, each increase of 100 MET-min/d in moderate-vigorous LTPA contributed with a 16% risk reduction in all-cause mortality (HR, 0.84; 95%CI, 0.77-0.91), a 27% risk reduction in CVD mortality (HR, 0.73; 95%CI, 0.61-0.87), and a 12% risk reduction in incident CVD (HR, 0.88; 95%CI, 0.79-0.99). No further benefits were observed beyond 400 MET-min/d. ConclusionsOur results support a nonlinear inverse relationship between moderate-vigorous LTPA and CVD and mortality. Benefits of PA are already observed with low levels of activity, with a maximum benefit around 3 to 5 times the current recommendations.

Influence of caseload on survival of patients (pts) with localized prostate cancer (PC) after definitive radiation therapy (DRT).

357 Background: We recently reported a significant all-cause mortality risk reduction associated with higher annual caseload for radical prostatectomy (RP)- (PMID 31398279). Here we explore this relationship in DRT. Methods: National Cancer Database (NCDB) was used to investigate outcomes of DRT in the United States. Beam radiation (BR), radioactive implant (RI) and both (BRRI) were included in analysis. Using overall survival (OS) as primary outcome, the relationship between facility annual caseload (FAC) for all PC pts and facility annual caseload (FARC) for those requiring DRT were examined using Cox model. Four volume groups (VG) were defined as VG1: &lt;50th, VG2: 50th-74th, VG3: 75th-89th and VG4: top 10 percentile of caseload. Results: Between 2004 and 2014, 355,247 pts underwent DRT. At a median follow up of 70.1 (95% CI: 1.0 - 143.1) months (mo), the median OS was 137.3 mo (136.9, 138.1). Using FAC/FARC, 19/14, 27/24, 24/26, and 30/37 % of pts were treated at VG 1 through 4, respectively. For FARC, median OS was 136.8 mo (134.9, 142.2+) for VG1 and 139.7 (137.7, 141.8+) mo for VG4, adjusted hazard ratio (aHR) 1.06 (1.03-1.09), p &lt;0.001. For FAC, median OS was 135.4 (134.1, 138.7) mo for VG1 and not reached for VG4, aHR 1.13 (1.09, 1.16), p &lt;0.001. In subgroups, FARC aHR for VG1 vs VG4 were 1.20 (1.16-1.25) for BR, 0.99 (0.93-1.05) for RI, and 1.15 (1.02-1.31) for BRRI. These numbers for FAC were 1.10 (1.06, 1.14), 1.12 (1.05, 1.19), and 1.24 (1.12, 1.39), respectively. Conclusions: There is a statistically significant OS advantage to DRT at a high annual caseload facility. This effect is more pronounced for BR and is influenced more noticeably by facility all PC caseload rather than DRT.[Table: see text]

Risks of Stroke and Mortality in Atrial Fibrillation Patients Treated With Rivaroxaban and Warfarin.

Background and Purpose- Oral anticoagulation therapy is standard of care for patients with nonvalvular atrial fibrillation to prevent stroke. This study compared rivaroxaban and warfarin for stroke and all-cause mortality risk reduction in a real-world setting. Methods- This retrospective cohort study (2011-2017) included de-identified patients from the Optum Clinformatics Database who started treatment with rivaroxaban or warfarin within 30 days following initial diagnosis of nonvalvular atrial fibrillation. Before nonvalvular atrial fibrillation diagnosis, patients had 6 months of continuous health plan enrollment and CHA2DS2-VASc score ≥2. Stroke severity was determined by the National Institutes of Health Stroke Scale, imputed based on machine learning algorithms. Stroke and all-cause mortality risks were compared by treatment using Cox proportional hazard regression, with inverse probability of treatment weighting to balance cohorts for baseline risk factors. Stratified analysis by treatment duration was also performed. Results- During a mean follow-up of 27 months, 175 (1.33/100 patient-years [PY]) rivaroxaban-treated and 536 (1.66/100 PY) warfarin-treated patients developed stroke. The inverse probability of treatment weighting model showed that rivaroxaban reduced stroke risk by 19% (hazard ratio [HR], 0.81 [95% CI, 0.73-0.91]). Analysis by stroke severity revealed risk reductions by rivaroxaban of 48% for severe stroke (National Institutes of Health Stroke Scale score, 16-42; HR, 0.52 [95% CI, 0.33-0.82]) and 19% for minor stroke (National Institutes of Health Stroke Scale score, 1 to <5; HR, 0.81 [95% CI, 0.68-0.96]), but no difference for moderate stroke (National Institutes of Health Stroke Scale score, 5 to <16; HR, 0.93 [95% CI, 0.78-1.10]). A total of 41 (0.31/100 PY) rivaroxaban-treated and 147 (0.44/100 PY) warfarin-treated patients died poststroke, 12 (0.09/100 PY) and 67 (0.20/100 PY) of whom died within 30 days, representing mortality risk reductions by rivaroxaban of 24% (HR, 0.76 [95% CI, 0.61-0.95]) poststroke and 59% (HR, 0.41 [95% CI, 0.28-0.60]) within 30 days. Conclusions- After the initial diagnosis of atrial fibrillation, patients treated with rivaroxaban versus warfarin had significant risk reduction for stroke, especially severe stroke, and all-cause mortality after a stroke. Findings from this observational study may help inform anticoagulant choice for stroke prevention in patients with nonvalvular atrial fibrillation.