Association of D-dimer levels with all-cause mortality in a healthy adult population: findings from the MOLI-SANI study

Elevated D-dimer levels are reportedly associated with higher risk of total mortality in patients with different diseases. We investigated whether a similar association could be found in a large, apparently healthy population. A large sample of individuals (N=17,359, 47% men, age ≥35 years) free of clinically recognized cardiovascular and cancer disease, for whom baseline D-dimer level was available, were studied within the MOLI-SANI cohort, randomly recruited from the general adult population of Southern Italy. The cohort was followed for a median of 4.2 years (73,807 person-years). D-dimer was measured in fresh citrated plasma by an automated latex-enhanced immunoassay. Hazard ratios were calculated using three Cox-proportional hazard models. Two hundred and eighty deaths were recorded. When modeled as a continuous variable, D-dimer level at baseline showed a non-linear association with mortality, whose incidence increased only in the upper quartile of the distribution (D-dimer ≥221 ng/mL). Thus, the group of individuals with D-dimer <221 ng/mL (75% of the population) acted as the reference group, while the remaining individuals were subdivided in tertiles and compared with the former group. Multivariable hazard ratios for mortality were 1.06, 1.45 and 1.97, respectively (P for trend <0.0001) across the three categories of increasing D-dimer concentration. The association was slightly attenuated, but still highly significant (P for trend 0.0002), after further adjustment for white blood cell count and C-reactive protein. In conclusion, Elevated D-dimer levels were independently associated with increased risk of death from any cause in an apparently healthy adult population.     

Familial aggregation and heritability of adult lung function: results from the Busselton Health Study.

Decreased spirometric indices are characteristic of asthma and other respiratory diseases. The aim of this study was to investigate the genetic and environmental components of variance of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) measured in adulthood in an Australian population-based sample of 468 Caucasian nuclear families. The inter-relationships of the genetic determinants of these traits with asthma and atopic rhinitis were also investigated. Serial cross-sectional studies were conducted in the town of Busselton in Western Australia between 1966 and 1981 and follow-up of previous attendees was undertaken in 1995. Data from each subject included in this study were from a single survey in adulthood (25-60 yrs of age) when the subject was as close to age 45 yrs as possible. Multivariate analysis suggested that FEV1 and FVC levels were associated with age, sex, height, tobacco smoke exposure, asthma and atopic rhinitis. After adjustment for relevant covariates, FEV1 levels had a narrow-sense heritability (h2N) of 38.9% (SE 9.1%). FVC levels had an h2N of 40.6% (SE 8.9%). Extended modelling demonstrated little overlap in the genetic determinants of asthma or atopic rhinitis and either FEV1 or FVC levels. The results of this study were consistent with the existence of important genetic determinants of adult lung function that are independent of asthma or other atopic disease, cigarette smoking, height, age or sex.     

Association between plasma viscosity and all-cause mortality: results from the MONICA-Augsburg Cohort Study 1984-92

Several studies have reported a strong association between various markers of the acute-phase response and death from cardiovascular diseases and all-cause mortality. Inflammation at a low level of intensity may be a common phenomenon associated with the majority of causes of death owing to chronic diseases. We sought to investigate the association of plasma viscosity with all-cause mortality in a cohort of apparently healthy men. The study population consisted of 964 men aged 45-64 years at entry, randomly selected from the general population and taking part in the first MONICA-Augsburg survey 1984-85. The main outcome measure was all-cause mortality. During 8 years of follow-up, there were 81 deaths (37 cardiovascular deaths, 23 deaths from cancer and 21 deaths from other causes). There was a strong positive and statistically significant age-adjusted relationship between plasma viscosity and all-cause mortality. The relative risk of death for a one standard deviation increase in plasma viscosity (0.070 mPa/s) was 1.45 [95% confidence interval (CI) 1.19-1.76]. After further adjusting for smoking, total cholesterol, body mass index, blood pressure and education, a relative risk of 1.41 (95% CI 1.14-1.74) resulted. Other risk variables had only negligible confounding effects. The relative risk of the median of the top quintile of the plasma viscosity distribution compared with the median of the bottom quintile, computed from the adjusted model, was 2.68 (95% CI 1.63-4.42). These findings suggest that plasma viscosity may have considerable potential to predict death from all causes in middle-aged men.     

Clinical and exercise test predictors of all-cause mortality: results from > 6,000 consecutive referred male patients

OBJECTIVE: To report the prevalence of abnormal treadmill test responses and their association with mortality in a large consecutive series of patients referred for standard exercise tests, with testing performed and reported in a standardized fashion. BACKGROUND: Exercise testing is widely performed, but few databases exist of large numbers of consecutive tests performed on patients referred for routine clinical purposes using standardized methods. Even fewer of the available databases have information regarding all-cause mortality as an outcome. METHODS: All patients referred for evaluation at two university-affiliated Veterans Affairs medical centers who underwent exercise treadmill testing for clinical indications between 1987 and 2000 were determined to be dead or alive using the Social Security death index after a mean 6.2 years (median, 7 years) of follow-up. Clinical and exercise test variables were collected prospectively according to standard definitions; testing and data management were performed in a standardized fashion using a computer-assisted protocol. All-cause mortality was utilized as the end point for follow-up. Standard survival analysis was performed, including Kaplan-Meier curves and a Cox hazard model. RESULTS: There were 6,213 male patients (mean +/- SD age, 59 +/- 11 years) who underwent standard exercise ECG treadmill testing over the study period with a mean follow-up duration of 6.2 +/- 3.7 years. There were no complications of testing in this clinically referred population, 78% of whom were referred for chest pain, or risk factors or signs or symptoms of ischemic heart disease. Overlapping thirds had typical angina or history of myocardial infarction (MI). Five hundred seventy-nine patients had prior coronary artery bypass surgery, and 522 patients had a history of congestive heart failure (CHF). Indications for testing were in accordance with published guidelines. Twenty percent died over the follow-up period, for an average annual mortality rate of 2.6%. Cox hazard function chose the following variables in rank order as independently and significantly associated with time to death: exercise capacity (metabolic equivalents < 5, age > 65 years, history of CHF, and history of MI. A score based on these variables (summing up the four variables [if yes = 1 point]) classified patients into low-risk, medium-risk, and high-risk groups. The high-risk group (score > or = 3) has a hazard ratio of 5.0 (95% confidence interval, 4.7 to 5.3) and a 5-year mortality rate of 31%. CONCLUSION: This comprehensive analysis provides rates of various abnormal responses that can be expected in patients referred for exercise testing at a typical medical center. Four simple variables combined as a score powerfully stratified patients according to prognosis.     

Predictors of all-cause mortality between ages 70 and 80: the Koganei study

The present paper explores predictors of all-cause mortality based on a longitudinal multidisciplinary study of 422 community residents (197 men, 225 women) aged 69-71 years at baseline examination. The 422 subjects were followed up for 10 years (1976-1986), during which time 102 (59 men, 43 women) died. The Cox proportional hazards model was used to examine the effects of baseline variables on a time-dependent 10-year mortality. Body mass showed a U-shaped relationship to mortality in both sexes. Ex-drinking, current-smoking, history of stroke, history of diabetes mellitus, low ADL and ST and/or T changes in ECG had significant and direct effects on mortality in both sexes or either sex. Whereas, level of education, current-drinking, grip strength, visual retention, and serum albumin revealed significantly inverse relationships to mortality.     

Preoperative coronary artery calcifications in veterans predict higher all-cause mortality in early-stage lung cancer: a cohort study

BackgroundLung cancer patients often have comorbidities that may impact survival. This observational cohort study examines whether coronary artery calcifications (CAC) impact all-cause mortality in patients with resected stage I non-small cell lung cancer (NSCLC).MethodsVeterans with stage I NSCLC who underwent resection at a single institution between 2005 and 2018 were selected from a prospectively collected database. Radiologists blinded to patient outcomes graded CAC severity (mild, moderate, or severe) in preoperative CT scans using a visual estimation scoring system. Inter-rater reliability was calculated using the kappa statistic. All-cause mortality was the primary outcome. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to compare time-to-death by varying CAC.ResultsThe Veteran patients (n=195) were predominantly older (median age of 67) male (98%) smokers (96%). The majority (68%) were pathologic stage IA. Overall, 12% of patients had no CAC, 27% mild, 26% moderate, and 36% severe CAC. Median unadjusted survival was 8.8 years for patients with absent or mild CAC versus 6.3 years for moderate and 5.9 years for severe CAC (P=0.01). The adjusted hazard ratio for moderate CAC was 1.44 (95% CI, 0.85–2.46) and for severe CAC was 1.73 (95% CI, 1.03–2.88; P for trend <0.05).ConclusionsThe presence of severe CAC on preoperative imaging significantly impacted the all-cause survival of patients undergoing resection for stage I NSCLC. This impact on mortality should be taken into consideration by multidisciplinary teams when making treatment plans for patients with early-stage disease.     

Weight loss increases and fat loss decreases all-cause mortality rate: results from two independent cohort studies.

OBJECTIVE: In epidemiological studies, weight loss is usually associated with increased mortality rate. Contrarily, among obese people, weight loss reduces other risk factors for disease and death. We hypothesised that this paradox could exist because weight is used as an implicit adiposity index. No study has considered the independent effects of weight loss and fat loss on mortality rate. We studied mortality rate as a function of weight loss and fat loss. DESIGN: Analysis of 'time to death' in two prospective population-based cohort studies, the Tecumseh Community Health Study (1890 subjects; 321 deaths within 16y of follow-up) and the Framingham Heart Study (2731 subjects; 507 deaths within 8y of follow-up), in which weight and fat (via skinfolds) loss were assessable. RESULTS: In both studies, regardless of the statistical approach, weight loss was associated with an increased, and fat loss with a decreased, mortality rate (P < 0.05). Each standard deviation (s.d.) of weight loss (4.6 kg in Tecumseh, 6.7 kg in Framingham) was estimated to increase the hazard rate by 29% (95% confidence interval CI), (14%, 47%, respectively) and 39% (95% CI, 25%, 54% respectively), in the two samples. Contrarily, each s.d. of fat loss (10.0 mm in Tecumseh, 4.8 mm in Framingham) was estimated to reduce the hazard rate 15% (95% CI, 4%, 25%) and 17% (95% CI, 8%, 25%) in Tecumseh and Framingham, respectively. Generalisability of these results to severely (that is, body mass index BMI) > or = 34) obese individuals is unclear. CONCLUSIONS: Among individuals that are not severely obese, weight loss is associated with increased mortality rate and fat loss with decreased mortality rate.     

Physical function and self-rated health status as predictors of mortality: results from longitudinal analysis in the ilSIRENTE study

Background

The longitudinal oustcomes of patients admitted to acute care for elders units (ACE) are mixed. We studied the associations between socio-demographic and functional measures with hospital length of stay (LOS), and which variables predicted adverse events (non-independent living, readmission, death) 3 and 6 months later.

Methods

Prospective cohort study of community-living, medical patients age 75 or over admitted to ACE at a teaching hospital.

Results

The population included 147 subjects, median LOS of 9 days (interquartile range 5–15 days). All returned home/community after hospitalization. Just prior to discharge, baseline timed up and go test (TUG, P < 0.001), bipedal stance balance (P = 0.001), and clinical frailty scale scores (P = 0.02) predicted LOS, with TUG as the only independent predictor (P < 0.001) in multiple regression analysis. By 3 months, 59.9% of subjects remained free of an adverse event, and by 6 months, 49.0% were event free. The 3 and 6-month mortality was 10.2% and 12.9% respectively. Almost one-third of subjects had developed an adverse event by 6 months, with the highest risk within the first 3 months post discharge. An abnormal TUG score was associated with increased adjusted hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.03 to 1.59, P = 0.03. A higher FMMSE score (adjusted HR 0.89, 95% CI 0.82 to 0.96, P = 0.003) and independent living before hospitalization (adjusted HR 0.42, 95% CI 0.21 to 0.84, P = 0.01) were associated with reduced risk of adverse outcome.

Conclusion

Some ACE patients demonstrate further functional decline following hospitalization, resulting in loss of independence, repeat hospitalization, or death. Abnormal TUG is associated with prolonged LOS and future adverse outcomes.     

Mediterranean dietary pattern and prediction of all-cause mortality in a US population: results from the NIH-AARP Diet and Health Study

BACKGROUND: The Mediterranean diet has been suggested to play a beneficial role for health and longevity. However, to our knowledge, no prospective US study has investigated the Mediterranean dietary pattern in relation to mortality. METHODS: Study participants included 214,284 men and 166,012 women in the National Institutes of Health (NIH)-AARP (formerly known as the American Association of Retired Persons) Diet and Health Study. During follow-up for all-cause mortality (1995-2005), 27,799 deaths were documented. In the first 5 years of follow-up, 5,985 cancer deaths and 3,451 cardiovascular disease (CVD) deaths were reported. We used a 9-point score to assess conformity with the Mediterranean dietary pattern (components included vegetables, legumes, fruits, nuts, whole grains, fish, monounsaturated fat-saturated fat ratio, alcohol, and meat). We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) using age- and multivariate-adjusted Cox models. RESULTS: The Mediterranean diet was associated with reduced all-cause and cause-specific mortality. In men, the multivariate HRs comparing high to low conformity for all-cause, CVD, and cancer mortality were 0.79 (95% CI, 0.76-0.83), 0.78 (95% CI, 0.69-0.87), and 0.83 (95% CI, 0.76-0.91), respectively. In women, an inverse association was seen with high conformity with this pattern: decreased risks that ranged from 12% for cancer mortality to 20% for all-cause mortality (P = .04 and P < .001, respectively, for the trend). When we restricted our analyses to never smokers, associations were virtually unchanged. CONCLUSION: These results provide strong evidence for a beneficial effect of higher conformity with the Mediterranean dietary pattern on risk of death from all causes, including deaths due to CVD and cancer, in a US population.     

Early functional disability predicts both all-cause and cardiovascular mortality in people with inflammatory polyarthritis: results from the Norfolk Arthritis Register

OBJECTIVE: To investigate the predictive value of early functional disability in patients with inflammatory polyarthritis (IP), for all-cause and cardiovascular disease (CVD) mortality. METHODS: 1010 subjects with new-onset IP from the Norfolk Arthritis Register were studied. All were seen at baseline and at 1 year. Health Assessment Questionnaire (HAQ) scores were obtained at both time points. Vital status at 10 years from registration was established through central records. Mortality (all-cause and CVD) per 1000 person-years were calculated by HAQ stratum (HAQ scores<1, 1-2 and>or=2). The predictive value of HAQ (per unit increase) at the two time points, adjusted for age at onset of symptom, sex and other factors found to predict mortality, was assessed using Cox regression models. The analysis was repeated for those who satisfied the 1987 American College of Rheumatology criteria for rheumatoid arthritis (RA) by 5 years. RESULTS: By 10 years, 171 (16.9%) subjects had died. 89 deaths (52%) were attributed to CVD. Mortality was greatest in the highest HAQ group at both time points. Following adjustment for other predictors, HAQ score at year 1 remained a significant predictor of all-cause mortality (HR 1.46; 95% CI 1.15 to 1.85) and CVD mortality (HR 1.49; 95% CI 1.12 to 1.97). The predictive value of HAQ at year 1 was similar in the RA subgroup. CONCLUSIONS: Our data show that at 1 year of follow-up, HAQ score is an important independent predictor of subsequent all-cause and CVD mortalities in people with IP and RA. Baseline HAQ scores are of less value.