Cardiovascular Disease-specific Mortality Research Articles

Longitudinal associations of polypharmacy and frailty with major cardiovascular events and mortality among more than half a million middle-aged participants of the UK Biobank

BackgroundStudies of the associations of polypharmacy and frailty with adverse health outcomes in middle-aged adults are limited. Furthermore, a potentially stronger association of polypharmacy with adverse health outcomes in frail than in non-frail adults is of interest. ObjectiveTo evaluate associations of frailty (assessed using a frailty index) and polypharmacy (defined as taking five or more drugs) with major cardiovascular events, cancer incidence, all-cause, cardiovascular disease-specific, and cancer-specific mortality. MethodsCox proportional hazards regression models were used to analyze 501,548 participants of the UK Biobank cohort study aged 40–69 years who were followed up for an average of 12 years. ResultsThe prevalence of pre-frailty and frailty were 43.2 % and 2.3 %, respectively, and that of polypharmacy was 18.3 %. Although strongly associated with each other, frailty and polypharmacy were independently, statistically significantly associated with major cardiovascular events, cardiovascular disease-specific, and all-cause mortality. In addition, the hazard ratios of polypharmacy were stronger among (pre-)frail than non-frail study participants. No profound associations with cancer incidence and cancer mortality were observed. No sex and age differences were observed. ConclusionsThis large cohort study showed that polypharmacy and frailty are independent risk factors for major cardiovascular events, cardiovascular disease-specific and all-cause mortality in both middle-aged (40–64 years) and older people (≥ 65 years). In addition, the hazard ratios of polypharmacy were stronger among (pre-)frail than non-frail study participants. This underlines the need to avoid polypharmacy as far as possible not only in older but also in middle-aged subjects (40–64 years), especially if they are pre-frail or frail.

Abstract 3425: Genetic predisposition to obesity and survival in women with breast cancer

Abstract Background. Higher body mass index (BMI) is associated with poor survival after breast cancer diagnosis. BMI is a heritable trait. A polygenic risk score (PRS) for BMI has been associated with cardiometabolic traits and found to modify weight loss interventions. Whether BMI genetic scores affect survival in women with breast cancer is unknown. Methods. This analysis was conducted in the Cancer Prevention Study II Nutrition cohort. Women diagnosed with non-metastatic breast cancer between 1992 and 2017 were included in the analysis if they had genotype data. Analyses were restricted to unrelated, postmenopausal women at the time of diagnosis who were of European ancestry (N=3,566). Deaths through 2020 were identified through linkage with the National Death Index. Primary cause of death was based on the International Classification of Disease codes. Pre-diagnosis BMI was self-reported (median 1.3 years from BMI measurement to diagnosis, interquartile range (IQR): 0.6, 1.9). We constructed a PRS using findings from a published meta-analysis of BMI genome wide association studies (GWAS) that included ~700,000 individuals and the PRSice tool.Hazard ratios (HR) and 95% confidence intervals (CI) between the PRS and all-cause mortality were estimated using Cox proportional hazards regression and Fine and Gray models for cause-specific mortality to account for competing risks. Models were adjusted for age and GWAS-specific statistically significant (P<0.05) principal components for population stratification. Mediation was estimated using the mediation R package. Results. The median age at diagnosis was 71.5 years (IQR: 66.3, 76.8). Most women were overweight (33.5%) or obese (18.4%) and were diagnosed with localized stage (63%) and estrogen receptor positive (65%) breast cancer. During a median follow-up of 14.5 years (IQR: 9.7-19.8), there were 1,825 (51.2%) deaths, including 301 breast cancer and 337 cardiovascular disease (CVD) specific deaths. In multivariable models, a 5 Kg/m2 increase in BMI was associated with increased risks of all-cause mortality (HR=1.09, 95% CI: 1.04, 1.15), breast cancer-specific mortality (HR=1.27, 95% CI: 1.13, 1.42), and CVD-specific mortality (HR=1.25, 95% CI: 1.11, 1.41). The PRS was highly predictive of pre-diagnostic BMI (P<0.001). A 1-standard deviation increase in the PRS was associated with statistically increased risk of all-cause mortality (HR=1.06, 95% CI: 1.02, 1.11). Risks of breast cancer (HR=1.07, 95% CI: 0.96, 1.19) or CVD (HR=1.01, 95% CI: 0.90, 1.12) specific mortality did not reach statistical significance. We estimated that 27% of the PRS and all-cause mortality association was mediated by BMI (95% CI: 12%, 91%; P=0.004). Conclusions. Women with breast cancer predisposed to higher BMI were at increased risk of all-cause mortality. A BMI-related PRS may be a useful tool to identify women with breast cancer in need of additional interventions and/or surveillance. Citation Format: Clara Bodelon, Adriana Lori, Mariah Landry, James Hodge, Parichoy Pal Choudhury, Ying Wang, Lauren E. McCullough, Alpa V. Patel, Lauren R. Teras. Genetic predisposition to obesity and survival in women with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3425.

Association of carotid atherosclerosis markers with all-cause and cardiovascular disease-specific mortality in persons with type 2 diabetes: a causal mediation analysis with glucose variation.

Glucose variation (GV) is independently associated with mortality in patients with diabetes. However, no study has examined the effects of carotid atherosclerosis markers on mortality after considering GV. Our purpose is to investigate the independent effects of carotid atherosclerosis markers in persons with type 2 diabetes (T2DM) after considering GV and the mediation effects of carotid atherosclerosis markers on associations between GV with cardiovascular disease (CVD) mortality. This study is a retrospective cohort study including 3628 persons with T2DM who were admitted to a medical center between January 01, 2001 and October 31, 2021. GV was defined as a coefficient of variation (CV) of repeated measurements within a year before the index date (date of first IMT assessment). Carotid atherosclerosis markers included intima-media thickness (IMT), plaque, and stenosis. The outcomes consisted of all-cause and expanded cardiovascular disease (CVD) mortality. Cox proportional hazards models were applied. Among the participants, 286 (7.9%) had IMT ≥ 2mm, 2834 (78.1%) had carotid plaque, and 464 (12.8%) had carotid stenosis ≥ 50%. When GV was considered, IMT, carotid plaque, and carotid stenosis were significant factors for all-cause mortality (except IMT considering HbA1c-CV) and expanded CVD mortality. IMT was a significant mediator in the associations of fasting plasma glucose (FPG)-CV with all-cause and expanded CVD mortality (2 and 3.19%, respectively), and carotid stenosis was a significant mediator in the association between FPG-CV and expanded CVD mortality (3.83%). Our statistical evaluations show suggests that carotid atherosclerosis markers are important predictors of CVD mortality in persons with T2DM if GV is considered. In addition, IMT and carotid stenosis were significant mediators in the association between GV and mortality.

Association of Symptomatic Dizziness With All-Cause and Cause-Specific Mortality

Dizziness is a highly prevalent complaint with wide-ranging causes and resultant morbidity. Whether symptomatic dizziness and its various manifestations are associated with all-cause and cause-specific mortality is unknown. To examine the associations of symptomatic dizziness and its manifestations with all-cause and cause-specific mortality. This cohort study is a mortality follow-up study based on the 1999-2004 National Health and Nutrition Examination Survey. The study cohort included adults 40 years and older who completed questions about symptomatic dizziness, including problems with dizziness, balance, falling, and positional dizziness, within the past 12 months. Respondents were linked to mortality data through December 31, 2019. Data were analyzed from February to August 2023. Self-reported symptomatic dizziness. All-cause and cause-specific (cardiovascular disease, diabetes, cancer, and unintentional injuries) mortality. Cox proportional hazard regression models were used to examine associations between symptomatic dizziness and all-cause and cause-specific mortality while adjusting for demographics and medical history. In this nationally representative cohort of 9000 middle-aged and older US adults (mean [SD] age, 61.8 [13.8] years; 4570 [50.8%] female), prevalence of symptomatic dizziness was 23.8%. Specifically, 18.3% reported problems with dizziness, 14.5% reported problems with balance, 5.7% reported problems with falling, and 3.8% reported dizziness when turning in bed (positional dizziness). At a median (range) of 16.2 (0.1-20.6) years of follow-up, all-cause mortality for adults with symptomatic dizziness was higher than for those without (45.6% vs 27.1%). Symptomatic dizziness was associated with elevated risk for cause-specific mortality from diabetes (hazard ratio [HR], 1.66; 95% CI, 1.23-2.25), cardiovascular disease (HR, 1.33; 95% CI, 1.12-1.55), and cancer (HR, 1.21; 95% CI, 0.99-1.47) but not unintentional injuries (HR, 0.98; 95% CI, 0.51-1.88). Reporting problems with balance or falling was associated with increased all-cause mortality (balance: HR, 1.27; 95% CI, 1.17-1.39; and falling: HR, 1.52; 95% CI, 1.33-1.73), cardiovascular disease-specific mortality (balance: HR, 1.41; 95% CI, 1.20-1.66; and falling: HR, 1.49; 95% CI, 1.15-1.94), and diabetes-specific mortality risks (balance: HR, 1.74; 95% CI, 1.26-2.39; and falling: HR, 2.01; 95% CI, 1.26-3.18). There was no association between positional dizziness and mortality (HR, 0.98; 95% CI, 0.82-1.19). In this cohort study, symptomatic dizziness was associated with increased risk for all-cause and diabetes-, cardiovascular disease-, and cancer-specific mortality. The imprecision of the effect size estimate for cancer-specific mortality prevents making a definitive conclusion. Future studies are needed to determine whether symptomatic dizziness indicates underlying health conditions contributing to mortality or if early intervention for imbalance and falls can reduce mortality risk.

Testosterone replacement therapy is not associated with increased prostate cancer incidence, prostate cancer-specific, or cardiovascular disease-specific mortality in Finnish men

Background Concerns have been expressed over the safety of testosterone replacement therapy (TRT) in men with late-onset hypogonadism (LOH). Previous studies have shown controversial results regarding the association of TRT with the risk of cardiovascular events or prostate cancer (PCa) incidence, aggressiveness, and mortality. This study explores the overall risk of PCa and risk by tumor grade and stage, as well as mortality from PCa and cardiovascular disease (CVD), among men treated with TRT compared to men without LOH and TRT use. Materials and methods The study included 78,615 men of age 55–67 years at baseline from the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). Follow-up started at randomization and ended at death, emigration, or a common closing date January 1st, 2017. Cox proportional hazards regression model with time-dependent variables and adjustment for age, trial arm, use of other medications, and Charlson comorbidity index was used. Comprehensive information on TRT purchases during 1995–2015 was obtained from the Finnish National Prescription Database. PCa cases were identified from the Finnish Cancer Registry and causes of death obtained from Statistics Finland. Results Over the course of 18 years of follow-up, 2919 men were on TRT, and 285 PCa cases were diagnosed among them. TRT users did not exhibit a higher incidence or mortality rate of PCa compared to non-users. On the contrary, men using TRT had lower PCa mortality than non-users (HR = 0.52; 95% CI 0.3–0.91). Additionally, TRT users had slightly lower CVD and all-cause mortality compared to non-users (HR = 0.87; 95% CI 0.75–1.01 and HR = 0.93; 95% CI 0.87–1.0, respectively). No time- or dose-dependency of TRT use was evident in any of the analyses. Conclusion Men using TRT were not associated to increased risk for PCa and did not experience increased PCa- or CVD-specific mortality compared to non-users. Further studies considering blood testosterone levels are warranted.

The association between atherogenic index of plasma and all-cause mortality and cardiovascular disease-specific mortality in hypertension patients: a retrospective cohort study of NHANES

BackgroundAtherogenic index of plasma (AIP), a marker of atherosclerosis and cardiovascular disease (CVD), was related to the all-cause mortality and CVD-specific mortality in a U-shape in general population respectively. However, no studies have investigated these associations in hypertensive populations. Herein, this study aims to explore the relationship of AIP and all-cause mortality and CVD-specific mortality in patients with hypertension in order to provide some reference for the risk hierarchical management of hypertension.MethodsDemographic and clinical data of 17,382 adult patients with hypertension were extracted from the National Health and Nutrition Examination Survey (NHANES) database in 2005–2018 in this retrospective cohort study. We used weighted univariate COX regression analysis to screen the covariates, and that weighted univariate and multivariate COX regression analyses to explore the association between AIP and all-cause mortality and CVD-specific mortality with hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses of age, gender, body mass index (BMI), CVD, diabetes mellitus (DM), antihyperlipidemic agents use, and hypotensive drugs use were also performed for further exploration of these relationships.ResultsThe average follow-up time was 97.10 months. A total of 2,844 patients died, and 971 of them died due to CVD. After adjusting for age, race, education level, marital status, poverty-income ratio (PIR), smoking, BMI, physical activity, antihyperlipidemic agents, DM, CVD, hypotensive drugs, estimated glomerular filtration rate (eGFR), and total energy intake, we found that both low [HR = 1.18, 95%CI: (1.07–1.32)] and high [HR = 1.17, 95%CI: (1.03–1.33)] levels of AIP were linked to an increased risk of all-cause mortality, and the U-shape association between AIP and CVD-specific mortality was also found [low AIP level: HR = 1.26, 95%CI: (1.05–1.51); high AIP level: HR = 1.26, 95%CI: (1.06–1.49)]. Furthermore, these relationships were existed in patients whose BMI > 25, were non-Hispanic White, with non-CVD, non-DM, non-antihyperlipidemic agents, and used hypertension drug (all P < 0.05).ConclusionAIP was associated with both all-cause mortality and CVD-specific mortality in patients with hypertension, but the specific role of AIP in prognosis in hypertensive populations is needed further exploration.

Association of the American Heart Association’s new “Life’s Essential 8” with all-cause and cardiovascular disease-specific mortality: prospective cohort study

BackgroundThe American Heart Association recently updated its construct of what constitutes cardiovascular health (CVH), called Life’s Essential 8. We examined the association of total and individual CVH metrics according to Life’s Essential 8 with all-cause and cardiovascular disease (CVD)-specific mortality later in life.MethodsData were from the National Health and Nutrition Examination Survey (NHANES) 2005–2018 at baseline linked to the 2019 National Death Index records. Total and individual CVH metric scores including diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure were classified as 0–49 (low level), 50–74 (intermediate level), and 75–100 (high level) points. The total CVH metric score (the average of the 8 metrics) as a continuous variable was also used for dose–response analysis. The main outcomes included all-cause and CVD-specific mortality.ResultsA total of 19,951 US adults aged 30–79 years were included in this study. Only 19.5% of adults achieved a high total CVH score, whereas 24.1% had a low score. During a median follow-up of 7.6 years, compared with adults with a low total CVH score, those with an intermediate or high total CVH score had 40% (adjusted hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.51–0.71) and 58% (adjusted HR 0.42, 95% CI 0.32–0.56) reduced risk of all-cause mortality. The corresponding adjusted HRs (95%CIs) were 0.62 (0.46–0.83) and 0.36 (0.21–0.59) for CVD-specific mortality. The population-attributable fractions for high (score ≥ 75 points) vs. low or intermediate (score < 75 points) CVH scores were 33.4% for all-cause mortality and 42.9% for CVD-specific mortality. Among all 8 individual CVH metrics, physical activity, nicotine exposure, and diet accounted for a large proportion of the population-attributable risks for all-cause mortality, whereas physical activity, blood pressure, and blood glucose accounted for a large proportion of CVD-specific mortality. There were approximately linear dose–response associations of total CVH score (as a continuous variable) with all-cause and CVD-specific mortality.ConclusionsAchieving a higher CVH score according to the new Life’s Essential 8 was associated with a reduced risk of all-cause and CVD-specific mortality. Public health and healthcare efforts targeting the promotion of higher CVH scores could provide considerable benefits to reduce the mortality burden later in life.

Association of phenotypic age acceleration with all-cause and cardiovascular disease-specific mortality in individuals with prediabetes and diabetes: results from the NHANES study.

Association of phenotypic age acceleration with all-cause and cardiovascular disease-specific mortality in individuals with prediabetes and diabetes: results from the NHANES study.

Low muscle mass is associated with a higher risk of all–cause and cardiovascular disease–specific mortality in cancer survivors

ObjectivesIndividuals with prior cancer diagnosis are more likely to have low muscle mass (LMM) than their cancer-free counterparts. Understanding the effects of LMM on the prognosis of cancer survivors can be clinically important. The aim of this study was to investigate whether risks for all-cause and cardiovascular disease (CVD)–specific mortality differ by status of LMM in cancer survivors and a matched cohort without cancer history. MethodsWe used cohort data from the 1999–2006 and 2011–2014 National Health and Nutrition Examination Survey. Participants included 946 adults surviving for ≥1 since cancer diagnosis and a matched cohort (by age, sex, and race) without cancer history (N = 1857). LMM was defined by appendicular lean mass and body height (men <7.26 kg/m2, women <5.45 kg/m2). Death was ascertained via the National Death Index and cause of death was assessed via International Classification of Diseases, Tenth Revision. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratio (aHR) and 95% confidence interval (CI) of LMM. ResultsThe mean age of cancer survivors and matched cohort was 60.6 y (SD 15) and 60.2 y (SD 14.9), respectively. The median follow-up was 10.5 y for survivors and 10.9 y for matched cohort. Overall, 22.2% of cancer survivors and 19.7% of the matched cohort had LMM, respectively. In all, 321 survivors (33.9%) and 495 participants (26.7%) in the matched cohort died during follow-up. CVD-specific deaths were identified in 58 survivors (6.1%) and 122 participants in the matched cohort (6.6%). The multivariable Cox model suggested that LMM was positively associated with all-cause (aHR, 1.73; 95% CI, 1.31–2.29) and CVD-specific (aHR, 2.13; 95% CI, 1.14–4.00) mortality in cancer survivors. The associations between LMM and risk for all-cause (aHR, 1.24; 95% CI, 0.98–1.56) and CVD-specific (aHR, 1.21; 95% CI, 0.75–1.93) mortality were not statistically significant in the matched cohort. ConclusionCancer survivors with LMM have an increased risk for all-cause and CVD-specific mortality. This increase appears to be larger than that in counterparts without cancer history.

S1185 Mortality in Patients With Lean NAFLD: A Systematic Review and Meta-Analysis

Introduction: While obesity is highly contributory to the development of nonalcoholic fatty liver disease (NAFLD), around 40% of patients with NAFLD are non-obese or lean. However, clinical outcomes of lean NAFLD are not well described, and the magnitude of the risk of mortality in lean patients with NAFLD compared to those who are non-lean remains uncertain. Methods: PubMed, Embase, and Cochrane library database were searched from inception to May 28, 2022 to identify eligible cohort studies assessing the risk of mortality among lean and non-lean patients with NAFLD. Meta-analysis was performed using random-effects models to obtain pooled relative risks (RRs) with 95% confidence intervals (CIs). Heterogeneity between studies was calculated using the Cochran Q test and I statistics. Results: Ten cohort studies with 109,151 patients with NAFLD were included. Patients with lean NAFLD had a comparable risk of all-cause mortality (RR, 1.09; 95% CI, 0.67 to 1.77; I-squared, 97.7%) and cardiovascular disease-specific mortality (RR, 1.12; 95% CI, 0.66 to 1.90; I-squared, 86.2%) to those with non-lean NAFLD. The pooled risk of liver disease-specific mortality was 1.88 times (RR; 95% CI, 1.02 to 3.45; I-squared, 29.4%) higher in patients with lean NAFLD. Conclusion: In patients with NAFLD, lean individuals have a higher risk of liver disease-specific mortality than non-lean individuals, however, the risk of all-cause mortality and cardiovascular mortality did not differ among the two groups. Further understanding of the risk factors, genetic and ethnic variabilities, and metabolic process of lean NAFLD phenotype is warranted. Furthermore, research is needed to determine mechanisms on how lean NAFLD is associated with worse liver mortality and to develop individualized treatment strategies for patients with lean NAFLD.Figure 1.: Comparative risk of all-cause mortality in lean and non-lean patients with NAFLD.

Association between sleep duration and cardiovascular disease specific mortality: A meta-analysis

Backgrounds: In this systemic review and meta-analysis, we concentrated on the association between sleep duration and cardiovascular disease (CVD) mortality because existing studies results were inconsistent. Methods: We searched for articles published before December 2021 in databases (PubMed and Web of Science). We used STATA 12.0 software to compute hazard ratios (HRs) with their 95% confidence intervals (CIs) to create a pooled effect size and 95% CI. Results: The meta-analysis showed that short sleep duration (&lt;7 hours/day) was associated with an increased CVD specific mortality, compared to normal sleep duration with a random effects model (HR = 1.12, 95% CI 1.08 to 1.16, I2 = 38.6%, p = 0.002). The meta-analysis showed that long sleep duration (&gt;7 hours/day) was associated with an increased CVD specific mortality, compared to normal sleep duration with a random effects model (HR = 1.23, 95% CI 1.18 to 1.29, I2 = 65.2%, p &lt; 0.001). Conclusions: We found that sleep duration that is either too short or too long is significantly associated with higher risk of CVD mortality. More relevant factors about sleep are needed to be evaluated on the associations between sleep and CVD. Further large-scale, well-designed, randomized controlled trials are needed to explore the associations.

Prevalence of High and Moderate Risk Nonalcoholic Fatty Liver Disease Among Adults in the United States, 1999–2016

Nonalcoholic fatty liver disease (NAFLD) subjects with fibrosis stage ≥2 are at high risk for mortality. We aimed to provide national estimates and temporal trends for NAFLD, based on different fibrosis severity. Data from the National Health and Nutrition Examination Survey (NHANES) (1999-2016) and NHANES III (1988-1994) were utilized. NAFLD was determined by ultrasound showing moderate to severe steatosis. For those without ultrasound, NAFLD was determined by the U.S. Fatty Liver Index score of ≥30. Hepatic fibrosis was assessed using Fibrosis-4 (FIB-4) score (FIB-4 <1.3= low risk; FIB-4 1.3-2.67= moderate risk; and FIB-4 >2.67= high risk). Annual percent change (APC) was calculated by using the joinpoint regression model. From NHANES III, 10,854 individuals were included (mean age 43.5 years; 47.5% male; 75.7% non-Hispanic White) and 37.7% had NAFLD. Among them, based on FIB-4, 80% had low-risk, 18.6% had moderate-risk, and 1.4% had high-risk NAFLD. NAFLD with moderate or high risk was more likely to have hypertension, hyperlipidemia, diabetes, cardiovascular disease, and metabolic syndrome than was low-risk NAFLD (all P < .02). NAFLD prevalence increased from 29.5% in 1999-2000 to 40.3% in 2015-2016 (APC, 2.78%; P < .02), moderate-risk NAFLD increased from 6.26% to 14.17% (APC, 5.34%; P < .02), and high-risk NAFLD increased from 0.49% to 1.15% (APC, 9.72%; P < .02). Independent predictors of advanced fibrosis were age (OR, 1.11; 95% CI, 1.06-1.17; P= .001) and diabetes (OR, 2.28; 95% CI, 1.03-5.05; P= .04). Compared with low-risk NAFLD, high-risk NAFLD was associated with significantly increased all-cause (HR, 1.53; 95% CI, 1.09-2.15; P= .01), cardiovascular disease-specific (HR, 1.99; 95% CI, 1.22-3.24, P < .01) and liver-specific (HR, 4.57; 95% CI, 1.03-28.79; P= .04) mortality. The prevalence of moderate- or high-risk NAFLD is increasing and is associated with increased all-cause, liver-related, and cardiovascular mortality.

Diets with higher insulinaemic potential are associated with increased risk of overall and cardiovascular disease-specific mortality.

Hyperinsulinaemia and insulin resistance have been proposed to be associated with mortality risk, and diet can modulate insulin response. However, whether dietary patterns with high insulinaemic potential are associated with mortality remains unknown. We prospectively examined the associations between hyperinsulinaemic diets and the risk of total and cause-specific mortality in a large nationally representative population. Dietary factors were assessed by 24-h recalls. Two empirical dietary indices for hyperinsulinaemia (EDIH) and insulin resistance (EDIR) were developed to identify food groups most predictive of biomarkers for hyperinsulinaemia (C-peptide and insulin) and insulin resistance (homoeostatic model assessment for insulin resistance), respectively. Deaths from date of the first dietary interview until 31 December 2015 were identified by the National Death Index. Multivariable hazard ratios (HR) and 95 % CI were calculated using Cox regression models. During a median follow-up of 7·8 years, 4904 deaths were documented among 40074 participants. For EDIH, the multivariable-adjusted HR (comparing extreme quintiles) were 1·20 (95 % CI 1·09, 1·32, P-trend<0·001) for overall mortality and 1·41 (95 % CI 1·15, 1·74, P-trend = 0·002) for CVD mortality. Similar associations were observed for EDIR with HR of 1·18 (95 % CI 1·07, 1·29, P-trend < 0·001) for total and 1·35 (95 % CI 1·09, 1·67, P-trend = 0·005) for CVD mortality. After further adjustments for BMI and diabetes, these positive associations were somewhat attenuated. Our findings suggested that diets with higher insulinaemic potential are associated with increased risk of overall and CVD-specific mortality.

Physical Activity after Colorectal Cancer Diagnosis and Mortality in a Nationwide Retrospective Cohort Study.

Simple SummaryPhysical activity can help to prevent colorectal cancer, but its importance after cancer diagnosis has not been validated. In this nationwide insurance data-based study of 43,596 colorectal cancer patients, a high level of physical activity after colorectal cancer diagnosis was negatively associated with a risk of death in both colon and rectal cancer patients, particularly in the surgically treated group. Our findings support the importance of the physical activity among colorectal cancer patients.Physical activity reduces the risk of colon cancer, but its prognostic impact after cancer diagnosis remains unclear. To evaluate the association between post-diagnosis activity and cause-specific mortality, we reconstructed a colorectal cancer patient cohort from the 2009–16 Korean National Health Insurance Service (NHIS) database. Subgroup analyses were performed by treatment group. In total, 27,143 colon cancer patients and 16,453 rectal cancer patients were included in the analysis (mean follow-up, 4.3 years; median 4.0 years). In the surgically treated group, a high level of activity (the weighted sum of the frequencies for walking, moderate, and vigorous activity greater than or equal to 3 times/week) was inversely associated with all-cause mortality (colon cancer: HR, 0.79; 95% CI, 0.72 to 0.88; rectal cancer: HR, 0.75; 95% CI, 0.66 to 0.86) and colorectal cancer-specific mortality (colon cancer: HR, 0.85; 95% CI, 0.76 to 0.97; rectal cancer: HR, 0.77; 95% CI, 0.66 to 0.90). No significant results were shown for cardiovascular disease-specific mortality. No association was shown in patients who received chemoradiotherapy without surgery. The present study may provide evidence for post-diagnosis physical activity as a prognostic factor in colorectal cancer, particularly in surgically treated early-stage patients.

Unrestrained eating behavior and risk of mortality: A prospective cohort study

Unrestrained eating behavior has been thought to be a proxy for diet frequency, timing, and caloric intake. We investigated the association of unrestrained eating with mortality risk in the Nurses' Health Study prospectively. During follow-up (1994-2016), 21,953 deaths were documented among 63,999 eligible participants in analyses of eating anything at any time, 22,120 deaths were documented among 65,839 participants in analyses of no concern with figure change. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Eating anything at any time was associated with an increased mortality from cancer (overall HR, 95%CI: 1.07, 1.00-1.13; driven by gastrointestinal tract cancer: 1.30, 1.10-1.54) and respiratory disease (1.16, 1.05-1.29), and decreased cardiovascular disease-specific mortality (0.92, 0.86-0.99), compared to those without this behavior; however, no association was observed between this behavior and all-cause mortality (1.02, 0.99-1.05). Women who reported having no concern with figure change experienced higher risk of mortality from all-cause (1.08, 1.05-1.11), cancer (1.08, 1.02-1.14), and respiratory disease (1.18, 1.08-1.30), compared to those not reporting this behavior. Their combined effect was associated with a higher all-cause (1.09, 1.04-1.14), cancer-specific (overall: 1.18, 1.09-1.28; gastrointestinal tract cancer: 1.36, 1.08-1.71; lung cancer: 1.09; 1.04-1.14), and respiratory disease-specific (1.30, 1.13-1.50) mortality, and was inversely associated with cardiovascular disease-specific mortality (0.88, 0.80-0.98), compared to those exhibiting the opposite. Unrestrained eating was associated with increased risk of all-cause, cancer-specific (particularly for gastrointestinal tract cancer and lung cancer), and respiratory disease-specific mortality, and decreased risk of cardiovascular disease-specific mortality.

Association Between Sugar-Sweetened Beverage Intake and Mortality Risk in Women: The California Teachers Study

BackgroundThe evidence linking sugar-sweetened beverage (SSB) intake and mortality risk is conflicting, and associations between various SSB subtypes and mortality remain unclear. ObjectiveTo examine the association between baseline SSB intake, subtypes of SSB intake, and mortality risk in women. DesignProspective cohort study. Participants/settingParticipants of the California Teachers Study (n = 100,314; median age = 53 years) free of cardiovascular disease, cancer, and diabetes at baseline (1995-1996) were followed from 1995 to 2015. Baseline SSB intake was defined as caloric soft drinks (regular soft drinks, not diet soda), sweetened bottled waters or teas, and fruit drinks; and was derived from a self-administered food frequency questionnaire. Main outcome measureMortality was ascertained via annual linkage with state- and nationwide mortality records and the National Death Index over 20 years. Statistical analysisMultivariable-adjusted Cox proportional hazards models were used to generate hazard ratios (HRs) and 95% CIs for assessing associations between SSB intake and mortality. Rare/never consumers were the comparator group. ResultsThere were a total of 14,143 deaths over 20 years (30.5% from cardiovascular disease; 29.2% from cancer). In women who consumed ≥ 7 servings/week of SSBs at baseline (4% of participants), the multivariable-adjusted HRs were not significant for all-cause, cardiovascular disease-specific, or cancer-specific mortality. Consuming ≥ 7 servings/week of baseline caloric soft drink was associated with a higher risk of all-cause (HR = 1.26, 95% CI 1.10 to 1.46; P for trend = 0.02) and cancer-specific (HR = 1.33, 95% CI 1.08 to 1.63; P for trend = 0.08) mortality. In secondary analyses, consuming ≥ 1.5 c/day of baseline SSBs was associated with all-cause mortality (HR = 1.12, 95% CI 1.02 to 1.24; P for trend = 0.01). ConclusionsAlthough the baseline frequency of total SSB intake was not significantly associated with mortality, consuming ≥ 7 servings/week of caloric soft drinks was associated with higher risk of all-cause and cancer-specific mortality. Findings support public health efforts to reduce caloric soft drink consumption.

Season of birth and cardiovascular mortality in atrial fibrillation: a population-based cohort study

Abstract Funding Acknowledgements Type of funding sources: None. Background. Month and season of birth may be indicators for a variety of prenatal and early postnatal exposures and they have been associated with life expectancy in adulthood. It is suggested that people born in the autumn on the northern hemisphere live longer than those born during the spring or summer, who may have an increase in cardiovascular disease specific mortality. Only few studies have followed populations longitudinally and no study has investigated the relation between season of birth and mortality in patients with established cardiac conditions. Methods. All patients with atrial fibrillation (AF) seen in an academic institution were identified in a database. We examined the clinical course of 8962 consecutive patients with AF seen over a 10-year period. The adverse outcomes were investigated during follow-up and we identified the causes of death. The relation between season of birth (autumn, winter, spring and summer) and mortality risk was assessed using Cox proportional hazard regression models using autumn as the reference. Analyses were also made separately for men and women. Results. In these 8962 patients (age 70 ± 10 years, CHA2DS2VASc score 3.1 ± 1.7), 1253 deaths were recorded during a follow-up of 2.5 ± 3.0 years (median 1.2, interquartile 4.3 years, yearly rate of death 5.5%) and 97% of causes of death were identified. Cardiovascular deaths accounted for 54% and 43% for non-cardiovascular. The three main causes of death were heart failure (29%), infection (18%) and cancer (12%). Season of birth was a significant predictor of cardiovascular mortality (overall p = 0.0006). The lowest mortality was seen for people born in autumn or winter and the highest mortality in those born in spring and summer. This was mainly related to a higher cardiovascular mortality in males (hazard ratio [HR] 1.46, 95%CI 1.10-1.93, p = 0.009 for males born in spring and HR 1.44, 95%CI 1.08-1.91, p = 0.01 for those born in summer when compared to males born in autumn as the reference) while this effect was not seen in women. In a model adjusted for age, CHA2DS2VASc score, HASBLED score, cardiovascular risk factors, other comorbidities, AF pattern, antithrombotic use and other cardiovascular drugs use, a higher cardiovascular mortality was still seen in males born in spring (adjusted HR 1.43, 95%CI 1.05-1.96, p = 0.03) or in summer (adjusted HR 1.46, 95%CI 1.07-1.99, p = 0.02) when compared to those born in autumn while this was not seen in women. Conclusion. Birth in spring or summer is associated with a higher risk of cardiovascular mortality in male AF patients. Further studies should aim at clarifying the mechanisms behind this association, which would support the so-called fetal origins hypothesis.

Association between body mass index and risk of cardiovascular disease-specific mortality among adults with hypertension in Shanghai, China.

The aim of our study was to examine the association between body mass index (BMI) and the risk of cardiovascular disease (CVD)-specific mortality among Chinese adults with hypertension by sex. This study included 212,394 adult hypertensive patients aged 20–85 years registered in the records of Minhang District during 2007–2018. Cox proportional hazards regression was performed to evaluate the association between BMI and CVD-specific mortality among Chinese adults with hypertension. There were 14,029 deaths over an average of 8.24 years (range, 0.19–11.96 years). The multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) across BMI categories (< 18.5 kg/m2, 18.5–24.9 kg/m2 [reference group], 25.0–29.9 kg/m2, and ≥ 30 kg/m2) for CVD-specific mortality were 1.37 (1.22–1.53), 1.00 (reference), 0.95 (0.90–1.01), and 1.21 (1.04–1.40) in males, and 1.44 (1.31–1.59), 1.00 (reference), 0.96 (0.91–1.01), and 1.04 (0.92–1.17) in females. A U-shaped relationship was observed between BMI and CVD-specific mortality (overall association P< 0.001; non-linearity P< 0.001). This association was attenuated in old age. This study revealed a U-shaped relationship between BMI and CVD-specific mortality among hypertensive men and women. In older people, overweight and obesity are potential factors that reduce the risk of CVD death.

Cardiovascular disease-specific mortality in 270,618 patients with non-small cell lung cancer

BackgroundThis study aimed to investigate the trend of cardiovascular disease (CVD)-specific mortality in patients with non-small cell lung cancer (NSCLC) and identify prognostic factors for CVD-specific death in stage NSCLC patients. MethodsIn this study, 270,618 NSCLC patients were collected from the Surveillance, Epidemiology, and End Results database. CVD- and NSCLC-specific cumulative mortality and proportion of death were calculated and graphically displayed to describe the probability of specific endpoints. Prognostic factors for CVD-specific mortality were evaluated by cause-specific hazard ratios (HR) with 95% confidence intervals (CI) using the competing risk model with non-cardiovascular death as competing risks. ResultsAmong all competing causes of death, lung cancer resulted in the highest cumulative mortality, followed by CVDs and other causes. In the proportion of cause-specific death, heart diseases accounted for approximately 5.3% of the total death, only secondary to primary cancer. In all three stages, higher age, squamous cell carcinoma, and no-or-unknown chemotherapy and/or radiotherapy were associated with a higher risk of CVD-specific death, while surgery treatment seemed to be a protective factor. Female gender was statistically related to CVD-specific death in stage I and III patients with HRs of 0.84 (0.78–0.91) and 0.84 (0.77–0.93), respectively. Interestingly, right-sided laterality was correlated with lower CVD-specific mortality with HR of 0.82 (0.74–0.90) in stage III. ConclusionsThis study illustrated the historical trend of CVD-specific death in NSCLC patients and assesses potential prognostic risk factors, highlighting the involvement of cardio-oncology teams in cancer treatment to provide optimal comprehensive care and long-term surveillance for cancer patients.

Association of sleep duration with all-cause and disease-specific mortality in US adults

BackgroundPrevious studies revealed inconsistent findings regarding the association between sleep duration and all-cause and disease-specific mortality. This study aimed to clarify the association of sleep duration with mortality using a...