Coffee consumption, cancer, and healthy aging: epidemiological evidence and underlying mechanisms.

This comprehensive review examines the role of coffee consumption in promoting healthy aging and its potential impact on cancer prevention. Previous research has shown that moderate coffee intake may contribute to extending healthspan and enhancing longevity through beneficial effects on cardiometabolic health and key biological processes involved in aging. However, the relationship between coffee consumption and cancer risk remains controversial. This review synthesizes longitudinal observational and interventional data on the effects of coffee consumption on overall and site-specific cancers, explores underlying biological mechanisms, and discusses clinical and public health implications. Additionally, the review highlights evidence from Mendelian randomization (MR) studies to assess potential causal relationships. Our findings suggest that coffee consumption is associated with a reduced risk of several cancers, including skin, liver, prostate, and endometrial cancers, and may also lower cancer recurrence rates, particularly in colorectal cancer. These protective associations appear consistent across different demographic groups, with the most significant benefits observed at consumption levels of three or more cups per day. However, evidence is inconclusive for many other cancers, and coffee consumption is consistently linked to an increased risk of lung cancer. MR studies generally do not support a strong causal relationship for most cancers, though some suggest potential protective effects for hepatocellular, colorectal, and possibly prostate cancers, with mixed results for ovarian cancer and an increased risk for esophageal cancer and multiple myeloma. The protective effect of coffee on liver and prostate cancer is supported by both observational and MR studies. The potential anti-cancer benefits of coffee are attributed to its bioactive compounds, such as caffeine, chlorogenic acids, and diterpenes, which possess antioxidant and anti-inflammatory properties. These compounds may reduce oxidative stress, inhibit cancer cell proliferation, induce apoptosis, and modulate hormone levels. The review emphasizes the need for further research to clarify dose-response relationships, causal associations, and the biological mechanisms underlying these associations. While coffee consumption appears to contribute to cancer prevention and healthy aging, caution is warranted due to the increased risk of certain cancers, highlighting the complexity of its health effects.

Diabetes and mortality risk in patients undergoing coronary angiography: The KARDIO study.

BACKGROUND: Diabetes is an established risk factor for adverse cardiovascular outcomes including mortality, but the relationship between diabetes and mortality risk in the presence of the extensive or diffuse form of coronary artery disease (CAD) is controversial. AIMS: We evaluated the association between diabetes and mortality risk in patients who underwent coronary angiography using a real-life clinical database. METHODS: We utilized the KARDIO registry, which comprised data on demographics, prevalent diseases, including diabetes status, cardiovascular risk factors, coronary angiographies, and other interventions in 79,738 patients. Hazard ratios (HRs) (95% confidence intervals [CIs]) for the association between prevalent diabetes and all-cause mortality were estimated. RESULTS: During a median follow-up of 5.5 years, 11,896 all-cause deaths occurred. In analyses adjusted for age, smoking status, hypertension, family history of CAD, dyslipidaemia, urgency of intervention, body mass index, sex, and sex-age interaction, the HR (95% CI) for mortality comparing diabetes with no diabetes was 1.44 (1.38, 1.50). Following additional adjustment for the degree of CAD (1-3 vessels disease) as confirmed by angiography, the HR (95% CI) for mortality remained similar 1.43 (1.36, 1.49). The association did not vary significantly across several relevant clinical characteristics except for a stronger association in those with a family history of CAD than those without (p = 0.034) and former smokers than nonsmokers (p = 0.046). CONCLUSION: In patients undergoing coronary angiography, diabetes is associated with an increased mortality risk, independent of several risk factors including the degree of CAD. The association may be modified by family history of CAD and smoking status.

Screening Sportsmen and Sportswomen Over Age 35: The Relevance of an Exercise Electrocardiogram. Data From the SEEPRED Study.

INTRODUCTION: The importance of exercise electrocardiogram (ECG) is still controversial in the prevention of cardiovascular events among sportsmen and sportswomen. The aim of this study was to assess the relevance of exercise ECG as a screening tool to prevent cardiovascular events when any cardiovascular disease (CVD) risk factors are present. METHODS: The study included leisure time asymptomatic sportsmen and sportswomen over age 35 evaluated from 2011 to 2016 at the University Hospital of Saint-Etienne (France). Major adverse cardiovascular events (MACE) and atrial fibrillation were collected at 3 years. RESULTS: Of the cohort of 2457 sportsmen and sportswomen (mean age 50.2 ± 9.4 years), 50 (2%) had a high-risk SCORE2. A total of 256 exercise ECGs (10%) were defined as positive, most of them due to silent myocardial ischemia (SMI) (n = 196; 8%). These 196 SMI cases led to 33 coronary angiograms (1%), which revealed 23 significant coronary stenoses requiring revascularization. In multivariate logistic regression analysis, having at least two CVD risk factors was independently associated with (1) positive exercise ECG (OR = 1.80 [95% CI: 1.29-2.52], p = 0.0006), with (2) suspected SMI (OR = 2.57 [95% CI: 1.10-6.02], p = 0.0304), with (3) confirmed SMI (OR = 8.20 [95% CI: 3.46-19.46], p < 0.0001) and with (4) cardiovascular events (MACE or atrial fibrillation) (OR = 6.95 [95% CI: 3.49-13.81], p < 0.0001) at 3 years (median). CONCLUSIONS: The study supports the European recommendations for the use of exercise ECG in evaluation of asymptomatic leisure time sportsmen over age 35. Having at least two CVD risk factors was the best predictor for presence of coronary artery stenosis that may increase the risk for adverse events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06024863.

Unraveling the link between cardiorespiratory fitness and cancer: a state-of-the-art review.

Cardiorespiratory fitness (CRF) not only reflects an individual's capacity to perform physical activities but also encapsulates broader effects on the basic biology of aging. This review aims to summarize the evidence on the influence of CRF on overall and site-specific cancer risks. It delves into the biological mechanisms through which CRF may exert its effects, explores the clinical implications of these findings, identifies gaps in the current evidence base, and suggests directions for future research. The synthesis of findings reveals that higher CRF levels (general threshold of > 7 METs) are consistently associated with a reduced risk of a range of cancers, including head and neck, lung, breast, gastrointestinal, particularly pancreatic and colorectal, bladder, overall cancer incidence and mortality, and potentially stomach and liver, bile duct, and gall bladder cancers. These inverse associations between CRF and cancer risk do not generally differ across age groups, sex, race, or adiposity, suggesting a universal protective effect of CRF. Nonetheless, evidence linking CRF with skin, mouth and pharynx, kidney, and endometrial cancers is limited and inconclusive. Conversely, higher CRF levels may be potentially linked to an increased risk of prostate cancer and hematological malignancies, such as leukemia and myeloma, although the evidence is still not conclusive. CRF appears to play a significant role in reducing the risk of several cancers through various biological mechanisms, including inflammation reduction, immune system enhancement, hormonal regulation, and metabolic improvements. Overall, enhancing CRF through regular physical activity offers a vital, accessible strategy for reducing cancer risk and extending the health span. Future research should aim to fill the existing evidence gaps regarding specific cancers and elucidate the detailed dose-response relationships between CRF levels and cancer risk. Studies are also needed to elucidate the causal relationships and mechanistic pathways linking CRF to cancer outcomes.

Estrogen and cardiovascular disease.

A large body of scientific research accumulated over the past twenty years documents the cardiovascular (CV) benefits of estradiol (E2) and progesterone (P4) in reproductive aged women. In contrast, accelerated development of CV disease (CVD) occurs in the absence of ovarian produced E2 and P4. Hormone replacement therapy (HRT) with E2 and P4 has been shown to cause no harm to younger menopausal women. This robust scientific data supports a reconsideration of the prescriptive use of E2 and P4 as preventative therapeutics for the reduction of CVD, even without additional large-scale studies of the magnitude of the Women's Health Initiative (WHI). With the current expanded understanding of the critical modulatory role played by E2 on a multitude of systems and enzymes impacting CVD onset, initiation of HRT shortly after cessation of ovarian function, known as the "Timing Hypothesis", should be considered to delay CVD in recently postmenopausal women.

Walking pace and the time between the onset of noncommunicable diseases and mortality: a UK Biobank prospective cohort study.

PURPOSE: To estimate time spent in various cardiovascular disease (CVD) and cancer states, according to self-reported walking pace. METHODS: In total, 391,744 UK Biobank participants were included (median age = 57 years; 54.7% women). Data were collected 2006-2010, with follow-up collected in 2021. Usual walking pace was self-defined as slow, steady, average, or brisk. Multistate modeling determined the transition rate and mean sojourn time in and across three different states (healthy, CVD or cancer, and death) upon a time horizon of 10 years. RESULTS: The mean sojourn time in the healthy state was longer, while that in the CVD or cancer state was shorter in individuals reporting an average or brisk walking pace (vs. slow). A 75-year-old woman reporting a brisk walking pace spent, on average, 8.4 years of the next 10 years in a healthy state; an additional 8.0 (95% CI: 7.3, 8.7) months longer than a 75-year-old woman reporting a slow walking pace. This corresponded to 4.3 (3.7, 4.9) fewer months living with CVD or cancer. Similar results were seen in men. CONCLUSIONS: Adults reporting an average or brisk walking pace at baseline displayed a lower transition to disease development and a greater proportion of life lived without CVD or cancer. AVAILABILITY OF DATA AND MATERIALS: Research was conducted using the UK Biobank resource under Application #33266. The UK Biobank resource can be accessed by researchers on application. Variables derived for this study have been returned to the UK Biobank for future applicants to request. No additional data are available.

Association between Serum Testosterone and Aortic Valve Stenosis: A Prospective Cohort Study.

Serum testosterone is associated with atherosclerotic cardiovascular disease, which shares risk factors with aortic stenosis (AS). The association between serum testosterone and AS has not been previously investigated. We aimed to assess the prospective association between serum testosterone and risk of AS. Serum testosterone was determined at baseline using a radioimmunoassay kit in 2577 men aged 42-61 years recruited into the Kuopio Ischemic Heart Disease prospective cohort study. Hazard ratios (HRs) with 95% confidence intervals (Cis) were estimated for AS. After a median follow-up of 27.2 years, 119 cases of AS were recorded. The risk of AS increased continuously with increasing serum testosterone across the range 25-39 nmol/L (p-value for nonlinearity = 0.49). In an analysis adjusted for age, body mass index, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking status, history of type 2 diabetes, history of coronary heart disease, and alcohol consumption, the HR (95% CI) for AS was 1.39 (1.10-1.76) per 10 nmol/L increase in serum testosterone. When alcohol consumption was replaced with physical activity, the HR (95% CI) was 1.38 (1.09-1.74). Comparing the bottom versus top third of serum testosterone, the corresponding (adjusted) risk estimates were 1.76 (1.11-2.81) and 1.76 (1.10-2.80), respectively. In middle-aged and older Finnish men, elevated levels of serum testosterone were associated with an increased risk of AS. Further research is needed to replicate these findings and assess any potential relevance of serum testosterone in AS prevention.

Self-reported walking pace and 10-year cause-specific mortality: A UK biobank investigation.

OBJECTIVE: To investigate associations of self-reported walking pace (SRWP) with relative and absolute risks of cause-specific mortality. PATIENTS AND METHODS: In 391,652 UK Biobank participants recruited in 2006-2010, we estimated sex- and cause-specific (cardiovascular disease [CVD], cancer, other causes) mortality hazard ratios (HRs) and 10-year mortality risks across categories of SRWP (slow, average, brisk), accounting for confounders and competing risk. Censoring occurred in September 30, 2021 (England, Wales) and October 31, 2021 (Scotland). RESULTS: Over a median follow-up of 12.6 years, 22,413 deaths occurred. In women, the HRs comparing brisk to slow SRWP were 0.74 (95% CI: 0.67, 0.82), 0.40 (0.33, 0.49), and 0.29 (0.26, 0.32) for cancer, CVD, and other causes of death, respectively, and 0.71 (0.64, 0.78), 0.38 (0.33, 0.44), and 0.29 (0.26, 0.32) in men. Compared to CVD, HRs were greater for other causes (women: 39.6% [6.2, 72.9]; men: 31.6% [9.8, 53.5]) and smaller for cancer (-45.8% [-58.3, -33.2] and - 45.9% [-54.8, -36.9], respectively). For all causes in both sexes, the 10-year mortality risk was higher in slow walkers, but varied across sex, age, and cause, resulting in different risk reductions comparing brisk to slow: the largest were for other causes of death at age 75 years [women: -6.8% (-7.7, -5.8); men: -9.5% (-10.6, -8.4)]. CONCLUSION: Compared to slow walkers, brisk SRWP was associated with reduced cancer (smallest reduction), CVD, and other (largest) causes of death and may therefore be a useful clinical predictive marker. As absolute risk reductions varied across age, cause, and SRWP, certain groups may particularly benefit from interventions to increase SRWP.

High Cardiorespiratory Optimal Point Values Are Related to Cardiovascular Mortality in Men Aged 46 to 70 Years: a Prospective Cohort Study

Abstract Background: Several hemodynamic and respiratory variables measured during cardiopulmonary exercise testing (CPX) have been shown to predict survival. One such measure is the cardiorespiratory optimal point (COP) that reflects the best possible circulation-respiration interaction, but there are still limited data on its relationship with adverse outcomes. Objective: To assess the association between COP and cardiovascular mortality in men aged 46 to 70 years. Methods: A sample of 2201 men who had anthropometric, clinical, and COP data obtained during cycling CPX between 1995 and 2022 was extracted from the CLINIMEX Exercise cohort. COP was identified as the minimal minute-to-minute VE/VO2 during CPX. Vital data were censored on October 31, 2022 for ICD-10-identified cardiovascular deaths. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs). Results: The mean ± standard deviation age was 57 ± 6 years and the median COP value was 24 (interquartile range = 21.2 to 27.4). During a mean follow-up of 4688 ± 2416 days, 129 (5.6%) patients died from cardiovascular causes. The death rates for low (< 28), high (28 to 30), and very high (> 30) categories of COP were 3.2%, 9.6%, and 18.7%, respectively. Following adjustment for age, history of myocardial infarction, diagnosis of coronary artery disease, and diabetes mellitus, the HR (95% CI) for cardiovascular mortality comparing very high versus low COP was 2.76 (1.87 to 4.07; p < 0.001). Conclusions: Our data indicate that, for a general population-based sample of men, COP > 30 represents a considerably higher risk for cardiovascular death. Information on COP could assist cardiovascular risk assessment in men.

Life's Essential 8 and the risk of cardiovascular disease death and all-cause mortality in Finnish men.

AIMS: The aim of the study was to examine the association between Life's Essential 8 (LE8) and the risk of cardiovascular and all-cause mortality. METHODS AND RESULTS: The LE8 was computed for 1662 men, aged 42-60 years, without pre-existing history of cardiovascular disease (CVD) at baseline in the Kuopio Ischaemic Heart Disease study. The LE8 factors include diet, physical activity, nicotine exposure, sleep, body mass index, blood pressure, blood glucose, and lipids. Each LE8 factor was scored between 0 and 100 points. The summation of all points generated the total LE8 score, which was categorized into quartiles ≤-420, >420-485, >485-550, and >550. Multivariable Cox regression models were used to estimate hazard ratios and 95% confidence intervals of LE8 scores for the outcomes. During a median follow-up of 30 years, 402 and 987 men died from CVD and any cause, respectively. The total LE8 score among participants ranged from 185 to 750. The higher the LE8 scores, the lower the risk of dying from CVD and all-cause. Following adjustment for age, alcohol consumption, and socio-economic status, every 50-unit increase in LE8 score was associated with 17% and 14% lower risk of CVD and all-cause deaths, respectively. Men within LE8 top quartile had 60% lower risk of CVD mortality when compared with those within the bottom quartile. CONCLUSION: Life's Essential 8 was strongly and inversely associated with the risk of CVD death and all-cause mortality among ageing men. Measures that promote optimal LE8 scores should be encouraged among the general population.

The association between the American Heart Association's Life's Essential 8 (LE8) and the risk of cardiovascular and all-cause mortality was examined using the Kuopio Ischaemic Heart Disease Risk Factor Study in Finland. The result supports continuous improvement in healthy behaviours and factors used in generating LE8 score, which may lower future risk of dying from heart disease. In this paper: • Men who had total LE8 score more than 550 had lower risk of dying from heart disease or any cause of death compared with those with LE8 score ≤ 420. • Increasing LE8 score by 50 can lower risk of dying from heart disease or any other cause.

Extracellular vesicles and high-density lipoproteins: Exercise and oestrogen-responsive small RNA carriers.

Decreased systemic oestrogen levels (i.e., menopause) affect metabolic health. However, the detailed mechanisms underlying this process remain unclear. Both oestrogens and exercise have been shown to improve metabolic health, which may be partly mediated by circulating microRNA (c-miR) signalling. In recent years, extracellular vesicles (EV) have increased interest in the field of tissue crosstalk. However, in many studies on EV-carried miRs, the co-isolation of high-density lipoprotein (HDL) particles with EVs has not been considered, potentially affecting the results. Here, we demonstrate that EV and HDL particles have distinct small RNA (sRNA) content, including both host and nonhost sRNAs. Exercise caused an acute increase in relative miR abundancy in EVs, whereas in HDL particles, it caused an increase in transfer RNA-derived sRNA. Furthermore, we demonstrate that oestrogen-based hormonal therapy (HT) allows the acute exercise-induced miR-response to occur in both EV and HDL particles in postmenopausal women, while the response was absent in nonusers.

Serum C-reactive protein-to-albumin ratio may be a potential risk indicator for venous thromboembolism: Findings from a prospective cohort study.

BACKGROUND AND AIMS: Circulating C-reactive protein (CRP) and albumin are commonly used inflammatory biomarkers. C-reactive protein-to-albumin ratio (CAR), a novel inflammatory biomarker, has been suggested to be a more reliable risk indicator compared to CRP or albumin alone. An inflammatory hypothesis has been postulated in VTE aetiology, but the association between CAR and VTE has not been investigated. We aimed to assess the prospective association of CAR with VTE risk. METHODS AND RESULTS: C-reactive protein and albumin were measured in serum samples at baseline from 2479 men aged 42-61 years. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated. During a median follow-up of 27.0 years, 168 VTE cases were recorded. In analysis adjusted for potential confounders, the HR (95% CI) for VTE comparing extreme tertiles of CAR was 1.49 (1.01-2.21), which was minimally attenuated on further adjustment for prevalent cancer, a potential mediator 1.48 (1.00-2.19). Serum CRP and albumin were each modestly associated with VTE risk in the same set of participants. CONCLUSION: In middle-aged and older men, elevated serum CAR may be associated with an increased risk of VTE. Further research is needed to replicate or refute these findings in other populations and assess if CAR may be of potential value in VTE management.

Associations of Cardiorespiratory Fitness With Estimated Remnant Cholesterol and Non-High-Density Lipoprotein Cholesterol in Healthy Men.

Remnant cholesterol (RC) and non-high-density lipoprotein cholesterol (non-HDL-C) may contribute to the residual risk for atherosclerotic cardiovascular disease. High cardiorespiratory fitness (CRF) is associated with favorable traditional lipid profiles, but its relation with RC and non-HDL-C remains unclear. We analyzed cross-sectional data on 4,613 healthy men (mean age 49 years). CRF was measured using peak oxygen uptake during incremental exercise testing and categorized into quartiles. RC was estimated as total cholesterol minus HDL-C and low-density lipoprotein cholesterol, and elevated RC was defined as ≥38 mg/100 ml (90 percentile). Non-HDL-C was calculated as total cholesterol minus HDL-C, and high non-HLD-C was defined as ≥190 mg/100 ml. CRF was inversely associated with RC (ß -0.31, 95% confidence interval [CI] -0.39 to -0.24) and non-HDL-C (ß -0.34, 95% CI -0.57 to -0.11) after adjustment for several risk factors. Each metabolic equivalent increment in CRF was associated with lower odds of having elevated RC (odds ratio [OR] 0.85, 95% CI 0.77 to 0.93) and non-HDL-C (OR 0.93, 95% CI 0.85 to 1.00) in multivariable analysis. Compared with the bottom quartile, the top quartile of CRF had significantly lower odds of elevated RC (OR 0.63, 95% CI 0.45 to 0.88) and non-HDL-C (OR 0.68, 95% CI 0.51 to 0.91). In conclusion, higher CRF was independently associated with lower levels of RC and non-HDL-C and lower odds of the prevalence of elevated RC and non-HDL-C in healthy men.

Cardiorespiratory Fitness Estimation Based on Heart Rate and Body Acceleration in Adults With Cardiovascular Risk Factors: Validation Study.

BACKGROUND: Cardiorespiratory fitness (CRF) is an independent risk factor for cardiovascular morbidity and mortality. Adding CRF to conventional risk factors (eg, smoking, hypertension, impaired glucose metabolism, and dyslipidemia) improves the prediction of an individual's risk for adverse health outcomes such as those related to cardiovascular disease. Consequently, it is recommended to determine CRF as part of individualized risk prediction. However, CRF is not determined routinely in everyday clinical practice. Wearable technologies provide a potential strategy to estimate CRF on a daily basis, and such technologies, which provide CRF estimates based on heart rate and body acceleration, have been developed. However, the validity of such technologies in estimating individual CRF in clinically relevant populations is poorly known. OBJECTIVE: The objective of this study is to evaluate the validity of a wearable technology, which provides estimated CRF based on heart rate and body acceleration, in working-aged adults with cardiovascular risk factors. METHODS: In total, 74 adults (age range 35-64 years; n=56, 76% were women; mean BMI 28.7, SD 4.6 kg/m2) with frequent cardiovascular risk factors (eg, n=64, 86% hypertension; n=18, 24% prediabetes; n=14, 19% type 2 diabetes; and n=51, 69% metabolic syndrome) performed a 30-minute self-paced walk on an indoor track and a cardiopulmonary exercise test on a treadmill. CRF, quantified as peak O2 uptake, was both estimated (self-paced walk: a wearable single-lead electrocardiogram device worn to record continuous beat-to-beat R-R intervals and triaxial body acceleration) and measured (cardiopulmonary exercise test: ventilatory gas analysis). The accuracy of the estimated CRF was evaluated against that of the measured CRF. RESULTS: Measured CRF averaged 30.6 (SD 6.3; range 20.1-49.6) mL/kg/min. In all participants (74/74, 100%), mean difference between estimated and measured CRF was -0.1 mL/kg/min (P=.90), mean absolute error was 3.1 mL/kg/min (95% CI 2.6-3.7), mean absolute percentage error was 10.4% (95% CI 8.5-12.5), and intraclass correlation coefficient was 0.88 (95% CI 0.80-0.92). Similar accuracy was observed in various subgroups (sexes, age, BMI categories, hypertension, prediabetes, and metabolic syndrome). However, mean absolute error was 4.2 mL/kg/min (95% CI 2.6-6.1) and mean absolute percentage error was 16.5% (95% CI 8.6-24.4) in the subgroup of patients with type 2 diabetes (14/74, 19%). CONCLUSIONS: The error of the CRF estimate, provided by the wearable technology, was likely below or at least very close to the clinically significant level of 3.5 mL/kg/min in working-aged adults with cardiovascular risk factors, but not in the relatively small subgroup of patients with type 2 diabetes. From a large-scale clinical perspective, the findings suggest that wearable technologies have the potential to estimate individual CRF with acceptable accuracy in clinically relevant populations.

Serum C-reactive protein-to-albumin ratio is a potential risk indicator for pneumonia: Findings from a prospective cohort study.

OBJECTIVE: Circulating C-reactive protein (CRP) and albumin are known biomarkers of systemic inflammation. C-reactive protein-to-albumin ratio (CAR), a novel biomarker, has been suggested to be a more reliable risk indicator for inflammatory conditions compared to CRP or albumin alone. Inflammatory processes underlie the pathophysiology of pneumonia, but the association between CAR and pneumonia has not been previously investigated. We aimed to assess the prospective association of CAR with pneumonia risk. METHODS: C-reactive protein and albumin were measured in serum samples at baseline from 2489 men aged 42-61 years, from the Kuopio Ischemic Heart Disease study. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated from Cox regression analysis. RESULTS: During a median follow-up of 26.1 years, 598 cases of pneumonia were recorded. In analysis adjusted for age, body mass index, smoking status, history of type 2 diabetes, prevalent coronary heart disease, history of asthma, history of chronic bronchitis, history of tuberculosis, alcohol consumption, socioeconomic status, leisure-time physical activity, and total energy intake, the HR (95% CI) for pneumonia comparing top versus bottom thirds of CAR was 1.62 (1.31-2.00). The corresponding adjusted risk for serum CRP was 1.67 (1.34-2.07). There was no evidence of an association between serum albumin and pneumonia risk. CONCLUSION: In middle-aged and older Finnish men, elevated serum CAR and CRP levels were each associated with an increased risk of pneumonia. Further research is needed to replicate these findings in other populations and assess the potential value of CAR in the prevention and management of pneumonia.

No evidence of a prospective relationship between serum zinc and venous thromboembolism in Caucasian men: a cohort study.

Serum zinc has been implicated as an important mediator of haemostasis and thrombosis. However, the nature and magnitude of any potential relationship between serum zinc and venous thromboembolism (VTE) is unknown. We aimed to evaluate the prospective association between serum zinc and VTE risk. We analyzed data involving 2472 men aged 42-61 years without a history of VTE in the Kuopio Ischemic Heart Disease population-based cohort study, with the assessment of serum zinc concentrations using atomic absorption spectrometry. Hazard ratios (95% confidence intervals [CIs]) for incident VTE were estimated. A total of 166 VTE cases occurred during a median follow-up of 27.1 years. The risk of VTE per 1 standard deviation increase in serum zinc in analysis adjusted for systolic blood pressure, body mass index, total cholesterol, triglycerides, smoking status, histories of type 2 diabetes and coronary heart disease, medication for dyslipidaemia, alcohol consumption, physical activity, and socioeconomic status was (HR 1.03; 95% CI 0.86-1.22), which remained similar (HR 1.04; 95% CI 0.87-1.23) following further adjustment for inflammation and history of cancer. Comparing the extreme tertiles of serum zinc, the corresponding adjusted HRs (95% CIs) were 0.92 (0.63-1.36) and 0.94 (0.64-1.39), respectively. Imputed results based on 2682 participants and 176 VTE events were consistent with the observed results. In middle-aged and older Finnish men, serum zinc is not associated with future VTE risk. Other large-scale prospective studies conducted in other populations are needed to confirm or refute these findings.

Cardiorespiratory fitness does not offset the increased risk of chronic obstructive pulmonary disease attributed to smoking: a cohort study.

Though evidence suggests that higher cardiorespiratory fitness (CRF) levels can offset the adverse effects of other risk factors, it is unknown if CRF offsets the increased risk of chronic obstructive pulmonary disease (COPD) due to smoking. We aimed to evaluate the combined effects of smoking status and CRF on incident COPD risk using a prospective cohort of 2295 middle-aged and older Finnish men. Peak oxygen uptake, assessed with a respiratory gas exchange analyzer, was used as a measure of CRF. Smoking status was self-reported. CRF was categorised as low and high based on median cutoffs, whereas smoking status was classified into smokers and non-smokers. Multivariable-adjusted hazard ratios with confidence intervals (CIs) were calculated. During 26 years median follow-up, 119 COPD cases were recorded. Smoking increased COPD risk 10.59 (95% CI 6.64-16.88), and high CRF levels decreased COPD risk 0.43 (95% CI 0.25-0.73). Compared with non-smoker-low CRF, smoker-low CRF was associated with an increased COPD risk in multivariable analysis 9.79 (95% CI 5.61-17.08), with attenuated but persisting evidence of an association for smoker-high CRF and COPD risk 6.10 (95% CI 3.22-11.57). An additive interaction was found between smoking status and CRF (RERI = 6.99). Except for CRF and COPD risk, all associations persisted on accounting for mortality as a competing risk event. Despite a wealth of evidence on the ability of high CRF to offset the adverse effects of other risk factors, it appears high CRF levels have only modest attenuating effects on the very strong association between smoking and COPD risk.

Associations of Sex Hormones and Hormonal Status With Arterial Stiffness in a Female Sample From Reproductive Years to Menopause.

Objective: Loss of sex hormones has been suggested to underlie menopause-associated increment in cardiovascular risk. We investigated associations of sex hormones with arterial stiffness in 19-58-years-old women. We also studied associations of specific hormonal stages, including natural menstrual cycle, cycle with combined oral contraceptives (COC) and menopausal status with or without hormone therapy (HT), with arterial stiffness. Methods: This study includes repeated measurements of 65 healthy women representing reproductive (n=16 natural, n=10 COC-users) and menopause (n=5 perimenopausal, n=26 postmenopausal, n=8 HT-users) stages. Arterial stiffness outcomes were aortic pulse wave velocity (PWVao) and augmentation index (AIx%) assessed using Arteriograph-device. Generalized estimating equation models were constructed to investigate associations of each hormone (wide age-range models) or hormonal stage (age-group focused models) with arterial stiffness. PWVao models with cross-sectional approach, were adjusted for age, relative fitness, fat mass and mean arterial pressure, while models with longitudinal approach were adjusted for mean arterial pressure. AIx% models used the same approach for adjustments and were also adjusted for heart rate. Results: Negative and positive associations with arterial stiffness variables were observed for estradiol and follicle-stimulating hormone, respectively, until adjustment for confounding effect of age. In naturally menstruating women, AIx% was higher at ovulation (B=3.63, p<0.001) compared to the early follicular phase. In COC-users, PWVao was lower during active (B=-0.33 - -0.57, p<0.05) than inactive pills. In menopausal women, HT-users had higher PWVao (B=1.43, p=0.03) than postmenopausal non-HT-users. Conclusions: When using wide age-range assessments covering reproductive to menopausal lifespan it is difficult to differentiate age- and hormone-mediated associations, because age-mediated influence on arterial stiffness seemed to overrule potential hormone-mediated influences. However, hormonal status associated differentially with arterial stiffness in age-group focused analyses. Thus, the role of sex hormones cannot be excluded. Further research is warranted to resolve potential hormone-mediated mechanisms affecting arterial elasticity.