Lowest Quartile Hazard Ratio Research Articles

Associations between serum uric acid and hepatobiliary-pancreatic cancer: A cohort study.

BACKGROUNDUric acid is the end product of purine metabolism. Previous studies have found that serum uric acid (SUA) levels are associated with the total cancer risk. However, due to the dual effect of uric acid on cancer, the relationship between the SUA levels and most specific-site cancer remains unclear.AIMTo investigate the associations between the SUA levels and incidence of hepatobiliary-pancreatic cancer.METHODSIn this prospective cohort study, 444462 participants free of cancer from the UK Biobank were included. The SUA levels were measured at baseline, and the incidence of hepatobiliary-pancreatic cancer was determined by contacting the cancer registry. The hazard ratios (HRs) and 95% confidence intervals (CIs) between the SUA levels and hepatobiliary-pancreatic cancer were investigated using multiple adjusted Cox regression models adjusted for potential confounders.RESULTSIn total, 920 participants developed liver, gallbladder, biliary tract or pancreatic cancer during a median of 6.6 yrs of follow-up. We found that the HR of pancreatic cancer in the highest SUA group was 1.77 (95%CI: 1.29-2.42) compared with that in the lowest group. After stratifying by gender, we further found that SUA was associated with an increased risk of pancreatic cancer only among the females (highest quartile vs lowest quartile HR 2.04, 95%CI: 1.35-3.08). Among the males, the SUA levels were positively associated with the gallbladder cancer risk (highest quartile vs lowest quartile HR 3.09, 95%CI: 1.28-7.46), but a U-shaped association with the liver cancer risk was observed (P-nonlinear = 0.03).CONCLUSIONSUA is likely to have gender-specific effects on hepatobiliary-pancreatic cancer. High SUA levels are a risk factor for pancreatic cancer in females and gallbladder cancer in males. A U-shaped association with the liver cancer risk was identified.

Association between regional body fat and cardiovascular disease risk among postmenopausal women with normal body mass index.

Central adiposity is associated with increased cardiovascular disease (CVD) risk, even among people with normal body mass index (BMI). We tested the hypothesis that regional body fat deposits (trunk or leg fat) are associated with altered risk of CVD among postmenopausal women with normal BMI. We included 2683 postmenopausal women with normal BMI (18.5 to <25 kg/m2) who participated in the Women's Health Initiative and had no known CVD at baseline. Body composition was determined by dual energy X-ray absorptiometry. Incident CVD events including coronary heart disease and stroke were ascertained through February 2017. During a median 17.9 years of follow-up, 291 incident CVD cases occurred. After adjustment for demographic, lifestyle, and clinical risk factors, neither whole-body fat mass nor fat percentage was associated with CVD risk. Higher percent trunk fat was associated with increased risk of CVD [highest vs. lowest quartile hazard ratio (HR) = 1.91, 95% confidence interval (CI) 1.33-2.74; P-trend <0.001], whereas higher percent leg fat was associated with decreased risk of CVD (highest vs. lowest quartile HR = 0.62, 95% CI 0.43-0.89; P-trend = 0.008). The association for trunk fat was attenuated yet remained significant after further adjustment for waist circumference or waist-to-hip ratio. Higher percent trunk fat combined with lower percent leg fat was associated with particularly high risk of CVD (HR comparing extreme groups = 3.33, 95% CI 1.46-7.62). Among postmenopausal women with normal BMI, both elevated trunk fat and reduced leg fat are associated with increased risk of CVD.

Hypercoagulability and the risk of recurrence in young women with myocardial infarction or ischaemic stroke: a cohort study

BackgroundWe aimed to investigate the role of hypercoagulability on the risk of lifetime cardiovascular recurrences after myocardial infarction or ischaemic stroke.MethodsYoung women (< 50 years) with either myocardial infarction (n = 197) or ischaemic stroke (n = 107) were followed between 1995 and 2012 in the RATIO follow-up study. To determine whether hypercoagulability affects the risk or recurrence, a coagulation score based on acquired and inherited markers was compiled and used in a quartile analysis. Hazard ratios (HRs) obtained from Cox proportional models and adjusted for several cardiovascular risk factors were used to compare quartiles of the coagulation score for the risk of recurrence.ResultsDuring a median follow-up of 19 years, 59 cardiovascular recurrences occurred. In patients with myocardial infarction no association was found between a high prothrombotic score and recurrences (highest quartile vs lowest quartile HR 0.7, 95% CI, 0.3–1.8). Conversely, ischaemic stroke patients with a high prothrombotic score showed a doubling in risk of long-term cardiovascular recurrences (HR 1.9, 95% CI 0.6–6.3) compared with ischaemic stroke patients and low levels of the score, with a dose response relationship.ConclusionsAn increased coagulation tendency might be associated with long-term cardiovascular risk in women with ischaemic stroke, but not in women with myocardial infarction.

Association Between Plasma Neutrophil Gelatinase-Associated Lipocalin and Cardiac Disease Hospitalizations and Deaths in Older Women.

BackgroundNeutrophil gelatinase‐associated lipocalin (NGAL) or lipocalin 2 may promote atherosclerosis and plaque instability leading to increased risk of cardiac events. We investigated the relationships between plasma NGAL, cardiovascular disease biomarkers, and long‐term cardiac events.Methods and ResultsThe study population consisted of 1131 ambulant older white women (mean age 75 years) without clinical coronary heart disease (CHD) and measures of plasma NGAL in the Perth Longitudinal Study of Ageing Women with 14.5‐year CHD and heart failure hospitalizations or death (events) captured using linked records. Over 14.5 years, 256 women had CHD events, while 118 had heart failure events. Per SD increase in log‐transformed NGAL there was a 35% to 37% increase in relative hazards for CHD and heart failure events in unadjusted analyses, which remained significant after adjustment for conventional risk factors for CHD events (hazard ratio 1.29, 95% CI 1.13–1.48, P<0.001) but not heart failure (P>0.05). Women in the highest 2 quartiles of NGAL had higher relative hazards for CHD events compared with women in the lowest quartile hazard ratio 1.61, 95% CI 1.08–2.39, P=0.019 and hazard ratio 1.97, 95% CI 1.33–3.93, P=0.001, respectively. These associations were independent of high‐sensitivity cardiac troponin I, homocysteine, and estimated renal function. NGAL correctly reclassified 1 in 4 women who sustained a CHD event up in risk and 1 in 10 women without CHD events down in risk.Conclusions NGAL was associated with increased risk of long‐term CHD events, independent of conventional risk factors and biomarkers. These findings provide mechanistic insight into the role of NGAL with cardiac events.

Abstract 047: Sedentary Behavior Increases Risk for Cardiovascular Disease in Older Women: The Objective Physical Activity and Cardiovascular Health (OPACH) Study

Background: Evidence on sedentary behavior and cardiovascular disease (CVD) is largely based on self-reported sedentary time. Furthermore, how sedentary time is accumulated (in longer vs. shorter bouts) may be related to CVD risk but has not been tested. Methods: Women (n=5638, mean age=79±7) with no history of myocardial infarction or stroke wore accelerometers for 4-7 days and were followed for up to 4 years for incident CVD. Hazard ratios (HR) and 95% confidence intervals (CIs) for CVD and coronary heart disease (CHD) events were estimated across quartiles of sedentary time and mean sedentary bout duration using Cox proportional hazard models adjusting for covariates. Separate models evaluated associations after adding moderate-to-vigorous physical activity (MVPA) and possible mediators: body mass index, diabetes, hypertension, systolic blood pressure, fasting glucose, HDL-cholesterol, and triglycerides. We then tested whether mean bout duration was associated with increased risk for CVD and CHD among women with above median sedentary time (≥10hr/day). Results: Covariate-adjusted HRs for CVD and CHD increased across quartiles of both sedentary time and mean bout duration (Table). All CHD associations remained significant but attenuated after adjustment for possible mediators. After adjustment for MVPA, highest vs. lowest quartile HRs (CI) for CHD were 1.6 (0.7-3.4; p-trend = .08) for sedentary time and 1.8 (0.9-3.5; p-trend = .047) for mean bout duration. Among women with high sedentary time, the HRs (CI) comparing the 75 th vs. 25 th percentile of mean bout duration were 1.05 (0.95-1.15) for CVD and 1.16 (1.01-1.34) for CHD. Conclusions: Both sedentary time and mean bout duration showed independent, dose-response associations with increased risk of CVD and CHD events in older women. Among women with high sedentary time, longer mean bout duration was associated with higher CHD risk. Taken together, this provides evidence that both total sedentary time and the way it is accumulated are predictive of incident CHD.

Adherence to the Dutch dietary guidelines is inversely associated with 20-year mortality in a large prospective cohort study.

The Dutch guidelines for a healthy diet aim to reduce major chronic diseases. However, supporting evidence on their overall association with all-cause and cause-specific mortality is limited. Recently, the Dutch Healthy Diet-index (DHD-index) has been developed to assess adherence to these guidelines. The aim was to examine the association between the DHD-index and all-cause mortality and deaths from cardiovascular disease (CVD), coronary heart disease (CHD), stroke and cancer. We followed 3593 men and women aged 55 years and older enrolled in the Rotterdam Study, a population-based prospective cohort study, from baseline in 1990-1993 to 2011. A validated 170-item food frequency questionnaire at baseline was used to calculate the DHD-index score (maximum 90 points). Cox proportional hazard models were used to estimate hazard ratios (HRs) adjusting for age, sex, total energy intake, smoking and educational level. During the 20-year follow-up, 1831 (51%) deaths were reported. Mean DHD-index score was 60.6 (s.d. 10.6). The score was inversely associated with all-cause mortality (highest vs lowest quartile HR 0.77; 95% confidence interval (CI) 0.67, 0.89). Inverse but non-significant associations were observed for mortality due to CVD (HR 0.74; 95% CI 0.55, 1.01), CHD (HR 0.60; 95% CI 0.34, 1.06) and stroke (HR 0.67; 95% CI 0.36, 1.22), whereas no association was observed with cancer mortality (HR 0.99; 95% CI 0.90, 1.11). A higher level of adherence to the Dutch dietary guidelines, as assessed with the DHD-index, was associated with a lower risk of all-cause mortality, probably due to an inverse association with cardiovascular causes of death.

Fruit and vegetable consumption and mortality in Eastern Europe: Longitudinal results from the Health, Alcohol and Psychosocial Factors in Eastern Europe study.

BackgroundIt is estimated that disease burden due to low fruit and vegetable consumption is higher in Central and Eastern Europe (CEE) and the former Soviet Union (FSU) than any other parts of the world. However, no large scale studies have investigated the association between fruit and vegetable (F&V) intake and mortality in these regions yet.DesignThe Health, Alcohol and Psychosocial Factors in Eastern Europe (HAPIEE) study is a prospective cohort study with participants recruited from the Czech Republic, Poland and Russia.MethodsDietary data was collected using food frequency questionnaire. Mortality data was ascertained through linkage with death registers. Multivariable adjusted hazard ratios were calculated by Cox regression models.ResultsAmong 19,333 disease-free participants at baseline, 1314 died over the mean follow-up of 7.1 years. After multivariable adjustment, we found statistically significant inverse association between cohort-specific quartiles of F&V intake and stroke mortality: the highest vs lowest quartile hazard ratio (HR) was 0.52 (95% confidence interval (CI): 0.28–0.98). For total mortality, significant interaction (p = 0.008) between F&V intake and smoking was found. The associations were statistically significant in smokers, with HR 0.70 (0.53–0.91, p for trend: 0.011) for total mortality, and 0.62 (0.40–0.97, p for trend: 0.037) for cardiovascular disease (CVD) mortality. The association was appeared to be mediated by blood pressure, and F&V intake explained a considerable proportion of the mortality differences between the Czech and Russian cohorts.ConclusionsOur results suggest that increasing F&V intake may reduce CVD mortality in CEE and FSU, particularly among smokers and hypertensive individuals.

Body size and risk for colorectal cancers showing BRAF mutations or microsatellite instability: a pooled analysis

How body size influences risk of molecular subtypes of colorectal cancer (CRC) is unclear. We investigated whether measures of anthropometry differentially influence risk of tumours according to BRAF c.1799T>A p.V600E mutation (BRAF) and microsatellite instability (MSI) status. Data from The Netherlands Cohort Study (n = 120,852) and Melbourne Collaborative Cohort Study (n = 40,514) were pooled and included 734 and 717 colorectal cancer cases from each study, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) for body mass index (BMI), waist measurement and height were calculated and compared for subtypes defined by BRAF mutation and MSI status, measured from archival tissue. Results were consistent between studies. When pooled, BMI modelled in 5 kg/m(2) increments was positively associated with BRAF wild-type (HR: 1.16, 95% CI: 1.08-1.26) and MS-stable tumours (HR: 1.15, 95% CI: 1.06-1.24). Waist measurement was also associated with BRAF wild-type (highest vs lowest quartile, HR: 1.59, 95% CI: 1.33-1.90) and MS-stable tumours (highest vs lowest quartile HR: 1.68, 95% CI: 1.31-2.15). The HRs for BRAF mutation tumours and MSI tumours were smaller and non-significant, but differences between the HRs by tumour subtypes were not significant. Height, modelled per 5-cm increase, was positively associated with BRAF wild-type and BRAF mutation tumours, but the HR was greater for tumours with a BRAF mutation than BRAF wild-type (HR: 1.23, 95% CI: 1.11-1.37, P(heterogeneity) = 0.03). Similar associations were observed with respect to height and MSI tumours (HR: 1.26, 95% CI: 1.13-1.40, P(heterogeneity) = 0.02). Generally, overweight increases the risk of CRC. Taller individuals have an increased risk of developing a tumour with a BRAF mutation or MSI.

S1238 Serum Lipids and the Risk of Developing Symptomatic Gallstones: A UK Prospective Cohort Study

Introduction The formation of gallstones may be influenced by alcohol consumption, physical activity and obesity through their effects on serum lipids. The aim of this study was to investigate if the serum levels of cholesterol, triglycerides, high density lipoprotein-cholesterol (HDL) and low density lipoprotein-cholesterol (LDL) were associated with the risk of symptomatic gallstones, for the first time in a European prospective cohort study. Methods A total of 21 850 men and women aged 45 to 74 years were recruited into the European Prospective Investigation into Cancer-Norfolk study between 1993 and 1997 and donated blood samples at enrolment. The cohort was then monitored over 14 years to identify participants who developed symptomatic gallstones, with each case reviewed by a physician to confirm the diagnoses. A cohort analysis was performed using Cox regression to estimate hazard ratios (HR) for developing symptomatic gallstones, in each gender, between quartiles of sex-specific serum lipid levels. In women, the HRs were adjusted for parity and hormone replacement therapy. Results During follow-up, 179 women and 81 men developed symptomatic gallstones at a median age of 61.8 years (range 42.7–76.5 years) with most patients presenting with biliary colic. Serum HDL was negatively associated with gallstones in both genders. For men, the highest compared to the lowest quartile of HR=0.22 (95% CI 0.10 to 0.53, p for trend across quartiles=0.001) and for women the HR=0.52 (95% CI 0.33 to 0.81, p for trend=0.004). Serum triglycerides were positively associated with gallstone disease in women (highest compared to lowest quartile HR=2.36, 95% CI 1.48 to 3.77, p for trend Conclusion This study confirmed that raised serum triglycerides are associated with an increased risk of symptomatic gallstones whereas raised serum HDL is associated with a decreased risk. These findings provide plausible biological mechanisms for how alcohol, physical activity and obesity influence the development of gallstones. If the latter are altered in public health programmes then the incidence of gallstones could be significantly reduced.