Mortality In Community-dwelling Adults Research Articles

THE ASSOCIATION OF FRAILTY AND MORTALITY IN OLDER ADULTS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF COHORT STUDY

Abstract Frailty is associated with poor health outcomes in later life, improving lifespan and death through different mechanisms. This study aimed to systematically review the epidemiological evidence from cohort studies investigating the association between frailty and all-cause mortality, and to determine if frailty affects mortality in older adults. We searched for studies published and indexed in 4 electronic databases (EMBASE, PubMed, Cochrane Library, and Web of Science) and manual search and identified 28 cohort studies before Dec 31, 2022. We include studies if their design was longitudinal; the exposure of interest was measured frailty; the endpoint of interest was mortality; they provided a risk estimate (i.e., hazard ratio [HR]) and the corresponding 95% CI for the association between frailty and mortality. They used different indexes as their frailty as exposed definitions. Two investigators independently screened the full-text articles for inclusion. We used a random-effects model to obtain pooled HRs. Thirty-one studies were included for qualitative review, of which twenty-eight were eligible for meta-analysis, and included 67,114 individuals from 16 countries. Compared with healthy adults, frail adults had a significantly higher mortality risk. The pooled HR for mortality per increment of 0.1 frailty of community-dwelling adults was 2.33 (95% CI 2.05-2.65; I2 76.9%). The present study demonstrated that frailty was not only significantly related to an increased mortality risk but was also a strong predictor of mortality in community-dwelling adults.

Influence of renal function on the ability of TyG Index to predict all-cause mortality

BackgroundThe association between triglyceride–glucose (TyG) index and poor prognosis remains controversial. Whether renal function status affects the ability of the TyG index to predict poor prognosis has not yet been elucidated and merits further studies.MethodsThis retrospective cohort study included 22,031 participants from communities in the U.S. By juxtaposing the TyG categories with the estimated glomerular filtration rate (eGFR, either < 60 mL/min/1.73m2 or ≥ 60 mL/min/1.73m2), participants were categorized into four distinct groups: (1) TyG_L/eGFR_H; (2) TyG_H/eGFR_H; (3) TyG_L/eGFR_L; and (4) TyG_H/eGFR_L. The endpoint was the all-cause mortality rate. Standard Kaplan–Meier plots were constructed and multifactor Cox regression analyses were carried out and restricted cubic spline regression analysis was utilized to assess the association between death and the TyG index for different renal function statuses.ResultsNo statistical differences were found in the TyG groups in participants with normal renal function after adjustment for all covariates (P = 0.070). However, in the high TyG index group with renal insufficiency, the risk of all-cause mortality rates was reduced by 18%. (HR, 0.82; CI, 0.69–0.98). The TyG index (high vs. low) and renal function (eGFR < 60 vs. eGFR ≥ 60) had statistically significant interactions with death (P < 0.001). When all covariates were adjusted, the risk of mortality for the TyG_L combined with eGFR_L group was 56% higher than that for the TyG_L combined with eGFR_H group (HR, 1.56; CI, 1.33–1.82). In the renal insufficiency population, a nonlinear relationship was observed between mortality and the TyG index, albeit with a differing pattern (P for nonlinearity < 0.001).ConclusionsWhile it has been known that TyG index was a prognosis marker of CVD, this research highlights that higher TyG index was associated with higher all-cause mortality rates for all participants. Furthermore, renal function status significantly moderates the effect of the TyG index on all-cause mortality in community-dwelling adults.

Health Effects of Vitamin D Supplementation: Lessons Learned From Randomized Controlled Trials and Mendelian Randomization Studies.

Vitamin D plays an important role in calcium homeostasis and many cellular processes. Although vitamin D supplements are widely recommended for community-dwelling adults, definitive data on whether these supplements benefit clinically important skeletal and extraskeletal outcomes have been conflicting. Although observational studies on effects of vitamin D on musculoskeletal and extraskeletal outcomes may be confounded by reverse causation, randomized controlled studies (RCTs) and Mendelian randomization (MR) studies can help to elucidate causation. In this review, we summarize the recent findings from large RCTs and/or MR studies of vitamin D on bone health and risk of fractures, falls, cancer, and cardiovascular disease, disorders of the immune system, multiple sclerosis, and mortality in community-dwelling adults. The primary analyses indicate that vitamin D supplementation does not decrease bone loss, fractures, falls, cancer incidence, hypertension, or cardiovascular risk in generally healthy populations. Large RCTs and meta-analyses suggest an effect of supplemental vitamin D on cancer mortality. The existence of extraskeletal benefits of vitamin D supplementations are best documented for the immune system especially in people with poor vitamin D status, autoimmune diseases, and multiple sclerosis. Accumulating evidence indicates that vitamin D may reduce all-cause mortality. These findings, in mostly vitamin D-replete populations, do not apply to older adults in residential communities or adults with vitamin D deficiency or osteoporosis. The focus of vitamin D supplementation should shift from widespread use in generally healthy populations to targeted vitamin D supplementation in select individuals, good nutritional approaches, and elimination of vitamin D deficiency globally. © 2023 American Society for Bone and Mineral Research (ASBMR).

Association between neutrophil percentage-to-albumin ratio (NPAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and long-term mortality in community-dwelling adults with heart failure: evidence from US NHANES 2005–2016

BackgroundHeart failure (HF) continues to be the major cause of hospitalizations. Despite numerous significant therapeutic progress, the mortality rate of HF is still high. This longitudianl cohort study aimed to investigate the associations between hematologic inflammatory indices neutrophil percentage-to-albumin ratio (NPAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and all-cause mortality in community-dwelling adults with HF.MethodsAdults aged 20 and older with HF in the US National Health and Nutrition Examination Survey (NHANES) database 2005–2016 were included and were followed through the end of 2019. Univariate and multivariable Cox regression analyses were performed to determine the associations between the three biomarkers and all-cause mortality. The receiver operating characteristics (ROC) curve analysis was conducted to evaluate their predictive performance on mortality.ResultsA total of 1,207 subjects with HF were included, representing a population of 4,606,246 adults in the US. The median follow-up duration was 66.0 months. After adjustment, the highest quartile of NPAR (aHR = 1.81, 95%CI: 1.35, 2.43) and NLR (aHR = 1.59, 95%CI: 1.18, 2.15) were significantly associated with increased mortality risk compared to the lowest quartile during a median follow-up duration of 66.0 months. Elevated PLR was not associated with mortality risk. The area under the ROC curve (AUC) of NPAR, NLR, and PLR in predicting deaths were 0.61 (95%CI: 0.58, 0.65), 0.64 (95%CI: 0.6, 0.67), and 0.58 (95%CI:0.55, 0.61), respectively.ConclusionsIn conclusion, elevated NPAR and NLR but not PLR are independently associated with increased all-cause mortality among community-dwelling individuals with HF. However, the predictive performance of NPAR and NLR alone on mortality was low.

Long-term prognostic value of trimethylamine N-oxide in community-based adults and patients with coronary heart disease

Abstract Background Trimethylamine N-oxide (TMAO) is an amine oxide generated by gut microbial metabolism. Emerging evidence suggests pro-atherosclerotic and pro-inflammatory properties of TMAO; however, the clinical utility of circulating TMAO in risk stratification is uncertain. Purpose We prospectively assessed relationships of plasma TMAO with long-term risk of all-cause, cardiovascular (CV) and non-CV mortality in community-dwelling adults and patients with coronary heart disease. Methods By Cox modelling, risk-associations were examined in the Hordaland Health Study (HUSK; 6393 community-based adults) and the Western Norway Coronary Angiography Cohort (WECAC; 4132 patients with suspected chronic coronary syndrome). Results Median follow-up time was 11.0 and 10.3 years in HUSK and WECAC, respectively. Following adjustments for established CV risk factors in HUSK, the HRs (95% CIs) comparing the 4th vs. 1st TMAO-quartile were 1.11 (0.88–1.40), 0.97 (0.65–1.46) and 1.17 (0.88–1.54) for all-cause, CV and non-CV mortality, respectively. Corresponding risk estimates in WECAC were 1.07 (0.86–1.32), 1.16 (0.83–1.62) and 1.02 (0.77–1.34). Similar results were observed in patients with angiographically significant coronary artery disease and patients with reduced left ventricular ejection fraction. Conclusion Plasma TMAO was not predictive of long-term all-cause, CV or non-CV mortality in patients with or without established coronary heart disease. This large-scale study does not support a role of TMAO for patient risk stratification in primary or secondary prevention. Funding Acknowledgement Type of funding sources: None.

Living alone and all-cause mortality in community-dwelling adults: A systematic review and meta-analysis.

SummaryBackgroundThe non-causal and causal associations, possible age and sex differences between living alone and all-cause mortality among adults were unclear. We aimed to assess the association and causal relation between living alone and all-cause mortality among community-dwelling adults, addressing the certainty of evidence, possible age and sex differences.MethodsWe searched Medline, Embase, and APA PsycINFO for cohort studies examining the association between living alone and all-cause mortality on November 19, 2021. We used the GRADE approach to assess certainty of evidence, and the Instrument for the Credibility of Effect Modification Analyses (ICEMAN) to evaluate credibility of subgroup inferences and conducted a meta-analysis of measures of association between living alone and mortality. The study was registered with PROSPERO, CRD42021290895.Findings18 cohort studies with 62,174 adults proved eligible. Living alone was associated with mortality (relative risk (RR) = 1.15, 95% confidence interval (CI) 1.08–1.23). Both age and sex modified the association (high and moderate credibility, separately). Living alone increased the risk of dying only in younger but not older individuals (ratio of RRs = 1.59, interaction P = 0.003; younger RR 1.41, 95% CI 1.17–1.71, high certainty for prognosis, low for causation; older RR = 1.05, 95% CI 0.91–1.22, moderate certainty for prognosis, very low for causation). Living alone increased risk to a greater extent in males than females (ratio of RRs = 1.39, 95% CI 1.14–1.70; interaction P = 0.001, males RR = 1.41, 95% CI 1.17–1.71, high certainty for prognosis, low for causation; females RR = 1.15, 95% CI 0.99–1.33; moderate for prognosis factor, very low for causation).InterpretationLiving alone is associated with increased mortality in individuals under 65 years (high certainty) but not with those over 75 years; the association may be causal (low certainty). Associations, and possibly effects, may be stronger in men than women.FundingNone.

Association between thyroid function, nursing home admission and mortality in community-dwelling adults over 80 years

PurposeThyroid deficiency may reduce mortality in older adults, but older adults prioritize independence over merely staying alive. We investigated the association between thyroid dysfunction and nursing home admission and all-cause mortality in community-dwelling older adults over 80. MethodsWe conducted a retrospective population-based open cohort study using data from laboratory registries covering 75% of Denmark supplemented by national registries. We included all community-dwelling older adults over 80 years with a first TSH measurement between 1996 and 2019. Participants with prior thyroid disorders or medication affecting the thyroid were excluded. Participants were followed from inclusion until nursing home admission, death or loss to follow-up due to emigration. ResultsWe included 272,495 participants at baseline. Median follow-time was 3.71 years in analyses of nursing home admissions and 4.00 years for all-cause mortality. Hypothyroidism was associated with lower nursing home admission (TSH 5–10 mIU/l: HR 0.85, 95% CI: 0.80–0.91, P < 0.001); TSH >10 mIU/l HR 0.68, 95% CI: 0.54–0.85, P = 0.001) and with reduced all-cause mortality (TSH >10 mIU/l: HR 0.81, 95% CI: 0.70–0.93, P = 0.002). The association between hyperthyroidism and nursing home admission was of little clinical significance while hyperthyroidism was associated with increased all-cause mortality hazard both for low (HR 1.16, 95% CI 1.13–1.19, P < 0.001) and suppressed (HR 95% CI: 1.14 1.07–1.21, P < 0.001) TSH. Conclusion: Hypothyroidism is associated with a reduced nursing home admission hazard and to a lesser extent all-cause mortality in community-dwelling adults over 80 years, while hyperthyroidism is associated with increased all-cause mortality but not hazard of nursing home admission.

Head Injury and All-Cause Mortality in Community-Dwelling Adults (P5-5.005)

Head Injury and All-Cause Mortality in Community-Dwelling Adults (P5-5.005)

Trimethyllysine predicts all-cause and cardiovascular mortality in community-dwelling adults and patients with coronary heart disease

AimsTrimethyllysine (TML) is involved in carnitine synthesis, serves as a precursor of trimethylamine N-oxide (TMAO) and is associated with cardiovascular events in patients with established coronary heart disease (CHD). We prospectively examined circulating TML as a predictor of all-cause and cardiovascular mortality in community-dwelling adults and patients with CHD.Methods and resultsBy Cox regression modelling, risk associations were examined in 6393 subjects in the community-based Hordaland Health Study (HUSK). A replication study was conducted among 4117 patients with suspected stable angina pectoris in the Western Norway Coronary Angiography Cohort (WECAC). During a mean follow-up of 10.5 years in the HUSK-cohort, 884 (13.8%) subjects died, of whom 287 from cardiovascular causes. After multivariable adjustments for traditional cardiovascular risk factors, the hazard ratio (HR) [95% confidence interval (95% CI)] for all-cause mortality comparing the 4th vs. 1st TML-quartile was 1.66 (1.31–2.10, P < 0.001). Particularly strong associations were observed for cardiovascular mortality [HR (95% CI) 2.04 (1.32–3.15, P = 0.001)]. Corresponding risk-estimates in the WECAC (mean follow-up of 9.8 years) were 1.35 [1.10–1.66, P = 0.004] for all-cause and 1.45 [1.06–1.98, P = 0.02] for cardiovascular mortality. Significant correlations between plasma TML and TMAO were observed in both cohorts (rs ≥ 0.42, P < 0.001); however, additional adjustments for TMAO did not materially influence the risk associations, and no effect modification by TMAO was found.ConclusionsElevated TML-levels were associated with increased risk of all-cause and cardiovascular mortality both in subjects with and without established CHD.

Muscle area and density and risk of all-cause mortality: The Multi-Ethnic Study of Atherosclerosis

BackgroundLean muscle plays critical roles in physical functioning and metabolism. However, little is known regarding associations between muscle and mortality in adults. ObjectiveThe purpose was to evaluate associations between abdominal muscle quantity (area) and quality (density) with risk of all-cause mortality in a diverse cohort free of cardiovascular disease. DesignData were taken from the Abdominal Body Composition, Inflammation, and Cardiovascular Disease ancillary study of the Multi-Ethnic Study of Atherosclerosis prospective cohort study. Participants were adults (45–85 years) free of extant cardiovascular disease, and of Hispanic, African American, Chinese, or Caucasian descent. Of the original 6814 MESA participants, a random, representative sample (n = 1974) participated in the ancillary body composition study. Abdominal muscle area and density were measured from computed tomography scans spanning L2-L4. Muscle density was measured as attenuation in Hounsfield units, and area was quantified as cm2. Gender-stratified cox proportional hazard models assessed the risk of all-cause mortality across gender-specific quartiles of muscle area and density adjusting for confounders, with area and density entered simultaneously. ResultsAt baseline, the mean age for men (n = 946) and women (n = 955) was 61.5 and 62.5 years and median follow-up time was 10.6 and 10.9 years, respectively. Muscle density was inversely associated with mortality, with the highest quartile of density showing a 73% reduction in risk for men (HR = 0.27, 95% CI = 0.14–0.51; p-trend<0.001) and 57% reduction for women (HR = 0.43, 95% CI = 0.18–1.01; p-trend = 0.04) compared to the lowest quartile when adjusting for mortality risk factors, lifestyle, BMI and visceral fat. There was no association between muscle area and all-cause mortality for men (p-trend = 0.58) or women (p-trend = 0.47). ConclusionsGreater abdominal muscle density, but not muscle area, is associated with markedly lower risk of all-cause mortality across a decade of follow up. Muscle quality may be a powerful predictor of mortality in community dwelling adults.

Subclinical Atherosclerosis Markers of Carotid Intima-Media Thickness, Carotid Plaques, Carotid Stenosis, and Mortality in Community-Dwelling Adults.

Carotid intima–media thickness (IMT), plaque, and stenosis are widely used as early surrogate markers of subclinical atherosclerosis and strong predictors of future deaths and cardiovascular events. Albuminuria is an indicator of generalized endothelial dysfunction that speeds up atherosclerosis. However, previous studies reporting these associations cannot rule out the confounding effect of albuminuria. We aimed to examine the independent and joint relationships between IMT markers and 10-year mortality in community-dwelling Taiwanese adults. This work was a community-based prospective cohort study consisting of 2956 adults aged at least 30 years recruited in 2007 and followed up through 2019. Cox proportional hazard regression models were used to examine associations of these subclinical atherosclerosis markers with mortality. During an average of 9.41 years of follow up, 242 deaths occurred. The mortality rate was 8.70 per 1000 person-years. Compared with those with carotid IMT less than 1.0 mm, persons with severely increased carotid IMT (≥2.0 mm) had an increased risk for death (hazard ratio (HR): 1.79; 95% confidence interval (CI): 1.07, 3.00). Compared with those without carotid plaque, persons with carotid plaque were more likely to have an increased risk for death (1.65; 1.21–2.32). Compared with those with carotid stenosis less than 25%, persons with carotid stenosis of 25–36% had a significant increased risk for death (1.57; 1.12–2.22). Considering these three IMT markers along with the traditional risk factors (c-statistic: 0.85) significantly increased their predictive ability of mortality compared with any individual variable’s predictive ability (all p-values < 0.001 for comparisons of c-statistic values). Carotid IMT measures, including IMT thickness, carotid plaque, and carotid stenosis were significant independent predictors of mortality. Our study supports evidence of blood pressure-related media thickening markers to assess future mortality risks in Chinese adults of general population.

Vitamin D and all-cause mortality in older adults &gt; 50 years - data from The Irish Longitudinal Study of Ageing

AbstractBackgroundLow 25-hydroxyvitamin D (25(OH)D) has been linked with adverse health outcomes, including cancer, cardiovascular disease and mortality. The Irish Longitudinal Study on Ageing (TILDA) has previously shown that 13.1% of the Irish population over 50 are deficient in 25(OH)D, after adjusting for seasonality. The aim of this study is to assess whether low 25(OH)D concentrations are associated with all-cause mortality in the over 50s in Ireland.MethodsData from Wave 1 (2009–2011) of TILDA, a prospective population representative study of community dwelling adults aged over 50, were used. Blood was obtained during the health assessment, and analysis of 25(OH)D was performed. Mortality was confirmed through official death records, and all participant deaths between baseline and March 2017 were included. Logistic regression assessed whether baseline levels of 25(OH) D, both continuous and categorised into deficient (25(OH)D &lt; 30 nmol/l), insufficient (30 &lt; = 25(OH)D &lt; 50 nmol/l) or sufficient (25(OH)D &gt; = 50 nmol/l), are associated with mortality.ResultsOf the 8,175 over 50s recruited, 25(OH)D data was available for 5,388 participants. Of these, 366 individuals had died prior to March 2017. Higher concentrations of 25(OH)D were associated with lower odds of mortality (OR 0.70; 95% CI 0.60, 0.81, p-value), controlling for confounders. On categorising 25(OH)D, those with insufficient 25(OH)D concentrations had higher odds of mortality than those with sufficient levels (OR 2.04; 95% CI 1.48, 2.8; p-value &lt; 0.001). Stratifying between men and women, there was no gender difference in this association.ConclusionInsufficient baseline 25(OH)D concentrations are associated with an increased odds of all-cause mortality in community dwelling adults over 50 in Ireland. Further research evaluating whether treatment of vitamin D deficiency improves mortality is warranted.

Abstract MP06: Vitamin K Status and Cardiovascular Disease: A Participant-Level Meta-Analysis

Introduction: A role for vitamin K in CVD has been proposed because vitamin K-dependent proteins are present in vascular tissue. In individual cohorts, low vitamin K status has been associated with increased CVD. We conducted a participant-level meta-analysis to summarize the association between circulating vitamin K and CVD in the Framingham Offspring Study, the Health, Aging, and Body Composition Study (Health ABC), and the Multi-ethnic Study of Atherosclerosis (MESA), three cohorts in which circulating vitamin K measures and confirmed cardiovascular events are available. Aim: To determine the association between vitamin K status and CVD in community-dwelling adults, overall and according to CVD risk and known risk factors. Methods: Circulating phylloquinone (vitamin K1) was measured from baseline fasting blood samples in 3626 participants and categorized as ≤0.5 nM, &gt;0.5 - ≤1.0 nM and &gt;1.0 nM. Multivariable Cox proportional hazards models assessed the association between circulating phylloquinone and risk of a composite of CVD and mortality. Results: Among the 3626 participants, mean baseline age was 65±11 yrs; 45% were men and 65% white. There were 1436 composite events over a median of 15.4 years. Participants with circulating phylloquinone &lt; 0.5 nM had a 21% higher risk for CVD and mortality compared to those with &gt;1.0nM [HR(95%CI)=1.21(1.06, 1.38)]. When stratified according to baseline CVD risk and risk factors, those with circulating phylloquinone &lt; 0.5 nM had a 27%-82% higher risk for CVD and mortality outcomes compared to those with &gt;1.0 nM ( Table ). Conclusion: Lower circulating phylloquinone was independently associated with a higher risk for CVD and mortality in community-dwelling adults, and more so among those at risk for CVD. Additional studies are needed to confirm our findings and clarify if segments of the population can derive cardiovascular benefit from improving vitamin K status.

Serum Matrix Metalloproteinase-7, Respiratory Symptoms, and Mortality in Community-Dwelling Adults. MESA (Multi-Ethnic Study of Atherosclerosis).

Matrix metalloproteinase-7 (MMP-7) has been implicated in interstitial lung disease pathobiology and proposed as a diagnostic and prognostic biomarker of idiopathic pulmonary fibrosis. To test associations between serum MMP-7 and lung function, respiratory symptoms, interstitial lung abnormalities (ILA), and all-cause mortality in community-dwelling adults sampled without regard to respiratory symptoms or disease. We measured serum MMP-7 in 1,227 participants in MESA (Multi-Ethnic Study of Atherosclerosis) at baseline. The 5-year outcome data were available for spirometry (n = 697), cough (n = 722), and dyspnea (n = 1,050). The 10-year outcome data were available for ILA (n = 561) and mortality (n = 1,227). We used linear, logistic, and Cox regression to control for potential confounders. The mean (±SD) serum MMP-7 level was 4.3 (±2.5) ng/ml (range, 1.2-24.1 ng/ml). In adjusted models, each natural log unit increment in serum MMP-7 was associated with a 3.7% absolute decrement in FVC% (95% confidence interval [CI] = 0.9-6.6%), a 1.6-fold increased odds of exertional dyspnea (95% CI = 1.3-1.9), a 1.5-fold increased odds of ILAs (95% CI = 1.1-2.1), and a 2.2-fold increased all-cause mortality rate (95% CI = 1.9-2.5). The associations with ILA and mortality tended to be stronger among never-smokers (P values for interaction 0.06 and 0.01, respectively). Serum MMP-7 levels may be a quantitative biomarker of subclinical extracellular matrix remodeling in the lungs of community-dwelling adults, which may facilitate investigation of subclinical interstitial lung disease.

Cardiorespiratory optimal point during exercise testing as a predictor of all-cause mortality

Introduction and AimThe cardiorespiratory optimal point (COP) is a novel index, calculated as the minimum oxygen ventilatory equivalent (VE/VO2) obtained during cardiopulmonary exercise testing (CPET). In this study we demonstrate the prognostic value of COP both independently and in combination with maximum oxygen consumption (VO2max) in community-dwelling adults. MethodsMaximal cycle ergometer CPET was performed in 3331 adults (66% men) aged 40-85 years, healthy (18%) or with chronic disease (81%). COP cut-off values of <22, 22-30, and >30 were selected based on the log-rank test. Risk discrimination was assessed using COP as an independent predictor and combined with VO2max. ResultsMedian follow-up was 6.4 years (7.1% mortality). Subjects with COP >30 demonstrated increased mortality compared to those with COP <22 (hazard ratio [HR] 6.86, 95% confidence interval [CI] 3.69-12.75, p<0.001). Multivariate analysis including gender, age, body mass index, and the forced expiratory volume in 1 s/vital capacity ratio showed adjusted HR for COP >30 of 3.72 (95% CI 1.98-6.98; p<0.001) and for COP 22-30 of 2.15 (95% CI 1.15-4.03, p<0.001). Combining COP and VO2max data further enhanced risk discrimination. ConclusionsCOP >30, either independently or in combination with low VO2max, is a good predictor of all-cause mortality in community-dwelling adults (healthy or with chronic disease). COP is a submaximal prognostic index that is simple to obtain and adds to CPET assessment, especially for adults unable or unwilling to achieve maximal exercise.

Cardiorespiratory optimal point during exercise testing as a predictor of all-cause mortality

Introduction and AimThe cardiorespiratory optimal point (COP) is a novel index, calculated as the minimum oxygen ventilatory equivalent (VE/VO2) obtained during cardiopulmonary exercise testing (CPET). In this study we demonstrate the prognostic value of COP both independently and in combination with maximum oxygen consumption (VO2max) in community-dwelling adults. MethodsMaximal cycle ergometer CPET was performed in 3331 adults (66% men) aged 40-85 years, healthy (18%) or with chronic disease (81%). COP cut-off values of <22, 22-30, and >30 were selected based on the log-rank test. Risk discrimination was assessed using COP as an independent predictor and combined with VO2max. ResultsMedian follow-up was 6.4 years (7.1% mortality). Subjects with COP >30 demonstrated increased mortality compared to those with COP <22 (hazard ratio [HR] 6.86, 95% confidence interval [CI] 3.69-12.75, p<0.001). Multivariate analysis including gender, age, body mass index, and the forced expiratory volume in 1 s/vital capacity ratio showed adjusted HR for COP >30 of 3.72 (95% CI 1.98-6.98; p<0.001) and for COP 22-30 of 2.15 (95% CI 1.15-4.03, p<0.001). Combining COP and VO2max data further enhanced risk discrimination. ConclusionsCOP >30, either independently or in combination with low VO2max, is a good predictor of all-cause mortality in community-dwelling adults (healthy or with chronic disease). COP is a submaximal prognostic index that is simple to obtain and adds to CPET assessment, especially for adults unable or unwilling to achieve maximal exercise.

NGAL Is Independently Associated with Cardiovascular Death and All-Cause Mortality in Community-Dwelling Older Adults with Stage A Heart Failure

Neutrophil gelatinase-associated lipocalin (NGAL) is a novel marker of acute kidney injury. Although it is expressed in atherosclerosis, its association with cardiovascular and all-cause mortality in community-dwelling adults has not been reported.