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Background: Most of the subjects eligible for annual low‐dose computed tomography (LDCT) lung screening will not develop lung cancer for their life. It is important to identify novel biomarkers that can help identify those at risk of developing lung cancer and improve the efficiency of LDCT screening programs. Objective: This study aims to investigate the association between the morphology of the pulmonary circulatory system (PCS) and lung cancer development using LDCT scans acquired in the screening setting. Methods: We analyzed the PLuSS cohort of 3635 lung screening patients from 2002 to 2016. Circulatory structures were segmented and quantified from LDCT scans. The time from the baseline CT scan to lung cancer diagnosis, accounting for death, was used to evaluate the prognostic ability (i.e., hazard ratio (HR)) of these structures independently and with demographic factors. Five‐fold cross‐validation was used to evaluate prognostic scores. Results: Intrapulmonary vein volume had the strongest association with future lung cancer (HR = 0.63, p < 0.001). The joint model of intrapulmonary vein volume, age, smoking status, and clinical emphysema provided the strongest prognostic ability (HR = 2.20, AUC = 0.74). The addition of circulatory structures improved risk stratification, identifying the top 10% with 28% risk of lung cancer within 15 years. Conclusion: PCS characteristics, particularly intrapulmonary vein volume, are important predictors of lung cancer development. These factors significantly improve prognostication based on demographic factors and noncirculatory patient characteristics, particularly in the long term. Approximately 10% of the population can be identified with risk several times greater than average. [ABSTRACT FROM AUTHOR]

Background We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a commercially available autoantibody biomarker test. Methods We designed a case-control study nested in 6 prospective cohorts, including 624 lung cancer participants who donated blood samples at most 3 years prior to lung cancer diagnosis and 624 smoking-matched cancer free participants who were assayed for 302 proteins. We used 470 case-control pairs from 4 cohorts to select proteins and train a protein-based risk model. We subsequently used 154 case-control pairs from 2 cohorts to compare the risk-discriminatory performance of the protein-based model with that of the Early Cancer Detection Test (EarlyCDT)-Lung and the PLCOm2012 model using receiver operating characteristics analysis and by estimating models' sensitivity. All tests were 2-sided. Results The area under the curve for the protein-based risk model in the validation sample was 0.75 (95% confidence interval [CI] = 0.70 to 0.81) compared with 0.64 (95% CI = 0.57 to 0.70) for the PLCOm2012 model (P difference =.001). The EarlyCDT-Lung had a sensitivity of 14% (95% CI = 8.2% to 19%) and a specificity of 86% (95% CI = 81% to 92%) for incident lung cancer. At the same specificity of 86%, the sensitivity for the protein-based risk model was estimated at 49% (95% CI = 41% to 57%) and 30% (95% CI = 23% to 37%) for the PLCOm2012 model. Conclusion Circulating proteins showed promise in predicting incident lung cancer and outperformed a standard risk prediction model and the commercialized EarlyCDT-Lung. [ABSTRACT FROM AUTHOR]

Background: Blood neutrophil to lymphocyte ratio (NLR) or lymphocyte count may be important markers for immune function. Previous work has shown higher NLR was associated with higher risk of hepatitis B‐related hepatocellular carcinoma (HCC). However, studies in non‐alcoholic fatty liver disease (NAFLD) patients are lacking. Methods: Utilizing the University of Pittsburgh Medical Center (UPMC) electronic health records, we created a retrospective cohort of 27,834 patients diagnosed with NAFLD from 2004 to 2018 with complete NLR data. After an average 5.5 years of follow‐up, 203 patients developed HCC. Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of HCC incidence associated with different levels of NLR and lymphocyte count. Results: Compared with the lowest tertile of NLR (<1.97), the highest tertile of NLR (≥3.09) was statistically significantly associated with a 43% higher risk of HCC incidence (HR = 1.43, 95% CI: 1.01–2.03, ptrend = 0.031) after adjustment for age, sex, race, body mass index, smoking status, history of type 2 diabetes, hyperlipidemia, hypertension, and fibrosis‐4 score category. Conversely the highest tertile of lymphocyte count (≥2.15 K/ul) was significantly associated with a 36% lower risk of HCC (HR = 0.64, 95% CI: 0.43–0.94, ptrend = 0.028) compared to the lowest tertile (<1.55 K/ul). There was no association between neutrophil count and HCC risk. Conclusions: Higher NLR and lower lymphocyte count are associated with significantly higher risk of HCC among NAFLD patients. These findings warrant further investigation of immune response and surveillance in association with HCC development in NAFLD patients. [ABSTRACT FROM AUTHOR]

It is difficult to identify people with nonalcoholic fatty liver disease (NAFLD) who are at high risk for developing hepatocellular carcinoma (HCC). A polygenic risk score (PRS) for hepatic fat (HFC‐PRS) derived from non‐Asians has been reported to be associated with HCC risk in European populations. However, population‐level data of this risk in Asian populations are lacking. Utilizing resources from 24,333 participants of the Singapore Chinese Health Study (SCHS), we examined the relationship between the HFC‐PRS and HCC risk. In addition, we constructed and evaluated a NAFLD‐related PRS (NAFLD‐PRS) with HCC risk in the SCHS. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of HCC incidence with both HFC‐PRS and NAFLD‐PRS. The HFC‐PRS and NAFLD‐PRS were highly correlated (Spearman r = 0.79, p < 0.001). The highest quartiles of both the HFC‐PRS and the NAFLD‐PRS were associated with significantly increased risk of HCC with HR of 2.39 (95% CI 1.51, 3.78) and 1.77 (95% CI 1.15, 2.73), respectively, compared with their respective lowest quartile. Conclusion: The PRS for hepatic fat content or NAFLD may be useful for assessing HCC risk in both Asian and European populations. The findings of this and prior studies support a potential causal role of genetically determined NAFLD in HCC development. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a major contributor to cancer death globally. Several studies showed some protections by certain individual dietary antioxidants against CRC development. Epidemiologic data on the composite dietary antioxidant index (CDAI) in relation to CRC risk are sparse. Using the Singapore Chinese Health Study, an ongoing prospective cohort consisting of 61 321 cancer‐free participants aged 45 to 74 years at baseline, a food‐based CDAI was calculated according to a previously established and validated method that included six food‐sourced antioxidants including vitamins A, C and E, manganese, selenium and zinc. Cox proportional hazard regression method was used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) for CRC associated with various levels of CDAI with adjustment for multiple potential confounders. After an average of 17.5 years of follow‐up, 2140 participants developed CRC. HRs (95% CIs) of CRC for quartiles 2, 3 and 4 of CDAI were 0.94 (0.83‐1.07), 0.86 (0.75‐1.00) and 0.80 (0.66‐0.98), respectively, compared to the lowest quartile (Ptrend =.02). This inverse association between CDAI and CRC risk was more apparent in women or those without a history of diabetes, without family history of CRC, never smokers or overweight/obese individuals. However, none of the heterogeneity tests for the CDAI‐CRC risk association reached statistical significance. Our findings suggest that food‐based antioxidants may be beneficial for reducing the risk of CRC in the general population. What's new? Epidemiological studies on individual dietary antioxidants such as vitamins and minerals and the risk of colorectal cancer have produced inconsistent results. In this large prospective Asian cohort study, the authors apply a recently developed composite dietary antioxidant index (CDAI) that includes vitamins A, C and E, manganese, selenium and zinc. The analysis shows that a higher CDAI is associated with a lower risk of developing CRC overall. These findings support the notion that food‐based antioxidants may offer a beneficial effect and provide a potential strategy for the primary prevention of colorectal cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Serine and glycine have an important role in the folate-dependent one-carbon metabolism. No prior epidemiologic study has evaluated the associations for serum levels of serine and glycine with pancreatic cancer risk. We performed a nested case-control study of 129 incident pancreatic cancer cases and 258 individually matched controls within the Shanghai Cohort Study, a prospective cohort study involving 18,244 male residents in Shanghai, China. We found that the risk of pancreatic cancer was reduced by more than 70% in individuals with elevated levels of serine and glycine in serum collected, on average, more than 10 years prior to cancer diagnosis. These novel findings support a protective role of serine and glycine against the development of pancreatic cancer in humans that might have an implication for pancreatic cancer prevention. Background. Serine and glycine play an important role in the folate-dependent one-carbon metabolism. The metabolism of serine and glycine has been shown to be associated with cancer cell proliferation. No prior epidemiologic study has investigated the associations for serum levels of serine and glycine with pancreatic cancer risk. Methods. We conducted a nested case-control study involved 129 incident pancreatic cancer cases and 258 individually matched controls within a prospective cohort study of 18,244 male residents in Shanghai, China. Glycine and serine and related metabolites in pre-diagnostic serum were quantified using gas chromatography-tandem mass spectrometry. A conditional logistic regression method was used to evaluate the associations for serine, glycine, and related metabolites with pancreatic cancer risk with adjustment for potential confounders. Results: Odds ratios (95% confidence intervals) of pancreatic cancer for the highest quartile of serine and glycine were 0.33 (0.14–0.75) and 0.25 (0.11–0.58), respectively, compared with their respective lowest quartiles (both p's < 0.01). No significant association with risk of pancreatic cancer was observed for other serine- or glycine related metabolites including cystathionine, cysteine, and sarcosine. Conclusion. The risk of pancreatic cancer was reduced by more than 70% in individuals with elevated levels of glycine and serine in serum collected, on average, more than 10 years prior to cancer diagnosis in a prospectively designed case-control study. These novel findings support a protective role of serine and glycine against the development of pancreatic cancer in humans that might have an implication for cancer prevention. [ABSTRACT FROM AUTHOR]

Background: Tea and coffee are widely consumed beverages. Tea flavonoids have been shown to inhibit lung tumorigenesis using in vitro and in vivo models. Conversely, coffee contains complex mixtures of biochemically active compounds, some of which may have genotoxic and mutagenic properties. However, previous epidemiologic studies have shown inconsistent results on tea and coffee in relation to lung cancer risk. Methods: The Singapore Chinese Health Study is a population-based prospective cohort of 63,257 Singaporean Chinese men and women, with an average of 17.7 years of follow-up. Information on tea and coffee consumption and other lifestyle factors was collected through in-person interviews at baseline. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations with adjustment for potential confounders. Results: There were 1486 incident lung cancer cases. Compared to non-daily coffee drinkers, HRs (95% CIs) of lung cancer risk for those consuming one, two, and three or more cups of coffee per day were 1.18 (1.02–1.36), 1.21 (1.05–1.40), and 1.32 (1.08–1.62) respectively (P for trend = 0.0034). The highest category of black tea consumption (at least 2 cups per day) was inversely associated with risk of lung cancer [HR (95% CI) = 0.73 (0.53–0.99)], particularly among men [HR (95% CI) = 0.67 (0.47–0.95)], compared to less-than-weekly black tea drinkers, although the interaction by sex was not statistically significant. Conclusions: Coffee beverage consumption was associated with higher risk of developing lung cancer. On the other hand, black tea intake was associated with lower risk of lung cancer among men in our cohort, and further studies are needed to confirm this association. [ABSTRACT FROM AUTHOR]

Background: Diet and inflammation have been suggested to be important risk factors for lung cancer. We examined the ability of the dietary inflammatory index (DII®) to predict lung cancer in the Singapore Chinese Health Study (SCHS). The DII is a diet quality index based on the literature linking foods and nutrients with inflammatory biomarkers. Patients and methods: Using data from the SCHS for 60,232 participants, including 1851 lung cancer cases, we investigated the associations of baseline DII scores calculated from a food frequency questionnaire with risk of developing lung cancer over an average of 17.6 years of follow-up. Hazard ratios (HR) were estimated using Cox regression, adjusting for smoking status and other risk factors. Results: After excluding cancers diagnosed in the first 2 years of follow-up, the DII was non-significantly associated with risk of lung cancer (HRQ5vsQ1 = 1.13; 95% CI 0.94–1.35; P-trend = 0.24) after adjusting for age, dialect group, sex, interview year, education, body mass index, total calorie intake, physical activity and various smoking variables. In stratified analysis, stronger, statistically significant associations were evident in current smokers (HR 1.44; 95% CI 1.11–1.86; Ptrend = 0.03, P for interaction = 0.003) and in male ever-smokers (HRQ5vsQ1 = 1.37; 95% CI 1.07–1.77; P-trend = 0.03). Conclusion: A pro-inflammatory diet, as shown by higher DII scores, is associated with an elevated risk of lung cancer for subjects with a history of smoking. Public health measures should be adopted to promote consumption of a healthy, anti-inflammatory diet to reduce the risk of lung cancer, especially in current and former smokers. [ABSTRACT FROM AUTHOR]

Background: Extreme telomere length has been previously reported to be associated with increased risk of gastric cancer. However, evidence from prospective studies on a relative large sample size with long-term follow-up to further corroborate previous study findings is meager.Methods: The association between peripheral blood leukocyte telomere length and risk of gastric adenocarcinoma was prospectively examined in a cohort of 26,540 middle-aged or older Chinese nested in the Singapore Chinese Health Study. Telomere length was determined using a validated qPCR-based method. The Cox proportional regression method was used to estimate hazard ratio (HR) and its 95% confidence interval (CI) of gastric adenocarcinoma associated with telomere length after adjustment for potential confounders. Restricted cubic spline analysis was applied to assess the nonlinear relationship between telomere length and gastric cancer risk.Results: A U-shaped association was found between telomere length and risk of gastric adenocarcinoma (Pnonlinearity = 0.020). Compared with the second quintile of telomere length, a statistically significant higher risk of gastric adenocarcinoma was associated with either the lowest quintile (HR = 1.63, 95% CI, 1.07-2.47) or the highest quintile (HR = 1.55, 95% CI, 0.97-2.47) of telomere length. This U-shaped relationship was more apparent in men and younger individuals.Conclusions: This is the first prospective study demonstrating a higher risk of gastric cancer to be associated with either extremely short or extremely long telomere length. Short and long telomere length may function differently in the early and late stages of gastric carcinogenesis. [ABSTRACT FROM AUTHOR]

Dietary catechins are phytochemicals with both antioxidative and prooxidative stress properties. Green tea is a major source of catechins and may be associated with hepatocellular carcinoma (HCC) risk, but the catechin-HCC relationship has not been evaluated using a biomarker-based approach. A nested case-control study of HCC (211 cases and 1,067 matched controls) was conducted within the Shanghai Cohort Study, which enrolled 18,244 men between 1986 and 1989. Concentrations of specific catechins, including epicatechin, epigallocatechin (EGC), and 4′-O-methyl-epigallocatechin, were measured in urine specimens that had been collected prior to HCC diagnosis. None of the catechins measured were associated with HCC risk. In stratified analyses, there was a statistically significant trend for an association of higher urinary EGC with increased HCC risk among subjects with positive serology for hepatitis B surface antigen (P for trend = 0.02). This positive EGC-HCC association became stronger for hepatitis B surface antigen–positive persons who also had low serum retinol levels (for detectable levels vs. undetectable levels, odds ratio = 2.62, 95% confidence interval: 1.25, 5.51). There was no evidence supporting a protective role of catechins in the development of HCC. Instead, exposure to high levels of catechins may increase the risk of developing HCC for high-risk individuals. [ABSTRACT FROM PUBLISHER]

OBJECTIVE -- Asian populations are documenting rapid increases in the rates of diabetes and hip fracture, but there are no prospective data linking both diseases in Asian studies. We investigated this association among a cohort of Chinese in Singapore. RESEARCH DESIGN AND METHODS-- A prospective cohort of 63,257 Chinese in the Singapore Chinese Health Study, established between 1993 and 1998, was followed up for a mean duration of 12 years. Diabetes status was ascertained by baseline interviews, and incidence of hip fracture post-enrollment was identified through a nationwide hospital discharge database. RESULTS-- The risk of hip fracture, after adjustment for other risk factors, was almost double among people with diabetes compared with people without diabetes (relative risk 1.98, 95% CI 1.71-2.29). When stratified by BMI, the increase in risk of hip fracture among people with diabetes relative to people without diabetes was similar in all four strata. There was a very strong dose-dependent relationship between duration of diabetes and risk of hip fracture (P for trend <0.0001). Compared with people without diabetes, the relative risk (95% CI) among subjects with diabetes for <5 years at recruitment was 1.40 (1.08-1.82), and this risk increased to 2.66 (2.04-3.47) among individuals with diabetes for ≥ 15 years. CONCLUSIONS-- Asians with diabetes, like their Western counterparts, experience an increased risk of hip fracture. Early assessment for osteoporosis and increased fracture risk, as well as prevention of falls, should be part of the management of diabetes. [ABSTRACT FROM AUTHOR]

Background: Incense use is an integral part of daily life in large parts of Asia. The burning of incense is a powerful producer of particulate matter and the smoke contains a multitude of well-characterized carcinogens. However, to the authors' knowledge, no convincing association has been reported between exposure to incense smoke and the development of cancer. Therefore, the relation between incense use and the risk of respiratory tract carcinomas was analyzed in a prospective cohort study.Methods: Between 1993 and 1998, a population-based cohort of 61,320 Singapore Chinese who were free of cancer and ages 45 to 74 years completed a comprehensive interview regarding living conditions and dietary and lifestyle factors. Through linkage to population-based registries, the cohort was followed through 2005 and cancer occurrence determined. The relative risk for these cancers associated with incense use was estimated using a Cox proportional hazards model.Results: A total of 325 upper respiratory tract (UPT) carcinomas and 821 lung carcinomas were observed during follow-up. Incense use was associated with a significantly increased risk of UPT carcinomas other than nasopharyngeal, whereas no overall effect was observed on lung cancer. The duration and intensity of incense use were associated with an increased risk of squamous cell carcinomas in the entire respiratory tract (P for trend = .004), whereas there was no significant association noted between incense use and nonsquamous cell carcinomas. The relative risk of squamous cell carcinomas among long-term incense users was 1.8 (95% confidence interval [95% CI], 1.2-2.6; P = .004) in the entire respiratory tract.Conclusions: The results of the current study indicate that long-term use of incense is associated with an increased risk of squamous cell carcinoma of the respiratory tract. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis. The increasing incidence rate of HCC in developed countries has been linked to increasing prevalence of metabolic dysfunction-associated fatty liver disease, which has characteristics of altered bile acid metabolism that may predate hepatocarcinogenesis. The aim of the present study was to assess the association of circulating bile acid levels in pre-diagnostic serum with the risk of developing HCC in a general population in Singapore. Primary conjugated bile acids were most strongly associated with increased risk of HCC whereas the ratios of secondary over primary bile acids were significantly associated with reduced risk. These results support a contributing role of dysmetabolism of bile acids in the development of HCC. The modulation of bile acid metabolism through alteration of gut microbiota may be an effective strategy for primary prevention against HCC in individuals with metabolic dysfunction-associated fatty liver disease. Hepatocellular carcinoma (HCC) is a commonly diagnosed malignancy with poor prognosis. Rising incidence of HCC may be due to rising prevalence of metabolic dysfunction-associated fatty liver disease, where altered bile acid metabolism may be implicated in HCC development. Thirty-five bile acids were quantified using ultra-performance liquid chromatography triple-quadrupole mass spectrometry assays in pre-diagnostic serum of 100 HCC cases and 100 matched controls from the Singapore Chinese Health Study. Conditional logistic regression was used to assess associations for bile acid levels with risk of HCC. Conjugated primary bile acids were significantly elevated whereas the ratios of secondary bile acids over primary bile acids were significantly lower in HCC cases than controls. The respective odds ratios and 95% confidence intervals of HCC were 6.09 (1.75–21.21) for highest vs. lowest tertile of cholic acid species and 30.11 (5.88–154.31) for chenodeoxycholic acid species. Doubling ratio of taurine-over glycine-conjugated chenodeoxycholic acid was associated significantly with 40% increased risk of HCC whereas doubling ratio of secondary over primary bile acid species was associated with 30–40% reduced risk of HCC. In conclusion, elevated primary bile acids and taurine over glycine-conjugated ratios were strongly associated with HCC risk whereas the ratios of secondary bile acids over primary bile acids were inversely associated with HCC risk. [ABSTRACT FROM AUTHOR]

Purpose: The incidence of Endometrial cancer (EC) has grown substantially in Asia over the past decade. However, few studies have addressed risk factors associated with EC incidence in Asian populations. We explored the association between reproductive and dietary risk factors and EC in the Singapore Chinese Health Study (SCHS), one of the largest prospective cohort studies in Asia.Methods: Data were collected from 34,028 ethnically Chinese women aged 45-74 residing in Singapore, enrolled between 1993 and 1998. Baseline demographic, dietary, and reproductive factors were collected via structured questionnaires. EC cases were identified from the Singapore Cancer Registry (n = 126) up to 2010. Cox proportional hazard models were used to analyze association between EC and personal, reproductive, and dietary factors.Results: The incidence of EC in this population was 28.8 per 100,000 person-years. Regardless of menopausal status, obesity (BMI ≥ 27) was associated with increased EC risk (HR = 2.22, 95% CI 1.26-3.92), while later age at menarche was associated with decreased EC risk (HR = 0.14, 95% CI 0.04-0.46). In postmenopausal women, later age at menopause was associated with increased EC risk (HR = 2.82, 95% CI 1.24-6.43). Lifestyle and nutritional factors were not associated with risk of EC in this cohort.Conclusions: This study is one of the largest cohort studies exploring EC risk factors in Asian populations. Our study identified similarities in EC risk factors for European and Asian populations, which potentially suggests that strategies developed for EC prevention in Western populations can be potentially appropriate for the Singapore Chinese population due to risk factor similarities. [ABSTRACT FROM AUTHOR]

Few data exist regarding the association of risk factor burden in middle age with lifetime risks for cardiovascular disease (CVD) and non-CVD death. In this study, participants in the Chicago Heart Association Detection Project in Industry aged 40 to 59 years in 1967 to 1973 were stratified into 5 groups on the basis of risk factor burden: favorable risk factor profile (untreated blood pressure ≤120/≤80 mm Hg, total cholesterol <200 mg/dl, nonsmoking, and body mass index <25 kg/m2); 0 elevated but ≥1 unfavorable; or any 1, any 2, or ≥3 elevated (systolic ≥140 mm Hg or diastolic ≥90 mm Hg or treated hypertension; total cholesterol ≥240 mg/dl; current smoking; or body mass index ≥30 kg/m2). Remaining lifetime risks for CVD and non-CVD death were estimated through the age of 85 years. Eight thousand thirty-three men and 6,493 women were followed for 409,987 person-years; 2,582 died of CVD, and 3,955 died of non-CVD causes. A greater risk factor burden was associated with a higher incidence of CVD and non-CVD death. Compared with participants with ≥3 risk factors, those with favorable profiles had substantially lower lifetime risks for CVD death (20.5% vs 35.2% in men, 6.7% vs 31.9% in women) and markedly longer median Kaplan-Meier survival (>35 vs 26 years in men, >35 vs 28 years in women). In conclusion, having favorable risk factors in middle age is associated with a lower lifetime risk for CVD death and markedly longer survival. These results should encourage efforts aimed at preventing the development of risk factors in younger subjects to decrease CVD mortality and promote longevity. [Copyright &y& Elsevier]

Purpose: Although personality traits may contribute to risk for cardiovascular disease (CVD), inconsistent findings have prompted efforts to refine their measurement to include only the hostile and aggressive components. Data are sparse on the “social avoidance” (SA) subscale that measures more indirectly negative traits such as shyness. Thus, we sought to examine the association between SA and CVD, coronary heart disease (CHD), and non-CVD death. Methods: A total of 2107 men (ages 40–55 years) free of baseline CVD were enrolled in 1957 in the Western Electric Study. SA was measured at study entry using the four-item subscale of the Cook-Medley hostility scale to divide the cohort into four groups according to the degree of social avoidance. CHD mortality, CVD mortality, and non-CVD mortality were determined by death certificate. Results: After 30 years of follow-up, SA was associated with CVD mortality for the highest vs. the lowest SA group in age-adjusted models (hazard ratio 1.39; 95% confidence interval [95% CI] 1.04–1.84) and after adjustment for traditional CVD risk factors (hazard ratio 1.49; 95% CI 1.12–2.00). After further adjustment for measures of hostility, the findings were similar. Findings for CHD mortality were similar. However, there was no significant association between SA and non-CVD mortality. Conclusions: Social avoidance is associated with CVD mortality but not with non-CVD mortality in middle-aged men. These findings suggest the hypothesis that social avoidance might promote CVD through physiologic, non-behavioral mechanisms. [Copyright &y& Elsevier]