Raymond Knutsen

The predictive value of resting electrocardiograms for 12-year incidence of coronary heart disease in the Honolulu heart program

The predictive value of electrocardiographic (ECG) abnormalities at baseline for subsequent risk of fatal and total coronary heart disease (CHD) was analyzed in a 12-year follow-up of 7682 men in the Honolulu Heart Program aged 45-68 who were free of CHD at baseline. Univariate analysis showed that men with major or minor ECG abnormalities, ST depression, high R wave, T-wave inversion, left ventricular hypertrophy or strain and premature ventricular contractions had considerably higher (2-10 fold) CHD incidence rates than those with normal ECG. When blood pressure, cigarette smoking, body mass index, alcohol use, physical activity, serum glucose, serum cholesterol, serum uric acid, age and years lived in Japan were taken into consideration through multivariate analysis, the ECG abnormalities retained significant associations with fatal and total CHD. This study demonstrated that resting ECG abnormalities were independent predictors of both total and fatal CHD.

Osteogenic protein-1 stimulates mRNA levels of BMP-6 and decreases mRNA levels of BMP-2 and -4 in human osteosarcoma cells.

Bone morphogenetic proteins (BMPs) are novel growth and differentiation factors that act on mesenchymal stem cells to initiate new bone formation in vivo and promote the growth and differentiation of cells in the osteoblastic lineage. In the present study, we examined the effects of recombinant human osteogenic protein-1 (also known as BMP-7) on the expression of related members of the BMP family using SaOS-2 and U2-OS, two human osteosarcoma cell strains. Evaluation of BMP-2, -4, and -6 mRNA expression indicates that OP-1 stimulated the mRNA levels of BMP-6 in both SaOS-2 cells (threefold) and U2-OS cells (fivefold) after 24 hours of treatment, while decreasing the mRNA levels of BMP-4 in SaOS-2 cells (80%) and BMP-2 and BMP-4 in U2-OS cells by 50% and 72%, respectively. BMP-2 mRNA expression, as examined by Northern blot analysis, was below detectable limits in SaOS-2 cultures. These results demonstrate that OP-1 modulates the mRNA expression of related members of the BMP family, suggesting a possible mode of action of OP-1 on the growth and differentiation of cells in the osteoblastic lineage in vitro.

The Association Between Incident Self-reported Fibromyalgia and Nonpsychiatric Factors: 25-years Follow-up of the Adventist Health Study

UNLABELLED The purpose of the study was to investigate the association between incident self-reported fibromyalgia (FM) and prior somatic diseases, lifestyle factors, and health behaviors among 3,136 women who participated in 2 cohort studies 25 to 26 years apart (the Adventist Health Study 1 and 2). The women completed a comprehensive lifestyle and medical history questionnaire at baseline in 1976. Information on new diagnosis of doctor-told FM was obtained at the second survey in 2002. A total of 136 women reported a diagnosis of FM during 25 years of follow-up, giving a period incidence of 43/1,000 or 1.72/1000 per year. In multivariable logistic regression analyses, a significant, dose-response association was found with number of allergies with OR of 1.61 (95% CI: .92-2.83) and 3.99 (95% CI: 2.31-6.88), (P[trend] < .0001), respectively, for 1 and 2 or more allergies versus none. A history of hyperemesis gravidarum was also associated with FM with OR of 1.32 (95% CI: .75-2.32) and 1.73 (95% CI: .99-3.03), (P[trend] < .05), respectively, for some or all pregnancies versus none. A positive association with smoking was also found with OR of 2.37 (95% CI: 1.33-4.23) for ever smokers versus never smokers. No significant association was found with number of surgeries, history of peptic ulcer, or taking medications to control various symptoms. PERSPECTIVE Smoking as well as prevalent allergies, and a history of hyperemesis gravidarum, seem to predict development of FM in women during 25 years of follow-up. This information may help in identifying persons at high risk of developing FM and thus initiate effective prevention strategies.

Are strict vegetarians protected against prostate cancer

BACKGROUND According to the American Cancer Society, prostate cancer accounts for ∼27% of all incident cancer cases among men and is the second most common (noncutaneous) cancer among men. The relation between diet and prostate cancer is still unclear. Because people do not consume individual foods but rather foods in combination, the assessment of dietary patterns may offer valuable information when determining associations between diet and prostate cancer risk. OBJECTIVE This study aimed to examine the association between dietary patterns (nonvegetarian, lacto-ovo-vegetarian, pesco-vegetarian, vegan, and semi-vegetarian) and prostate cancer incidence among 26,346 male participants of the Adventist Health Study-2. DESIGN In this prospective cohort study, cancer cases were identified by matching to cancer registries. Cox proportional hazards regression analysis was performed to estimate HRs by using age as the time variable. RESULTS In total, 1079 incident prostate cancer cases were identified. Around 8% of the study population reported adherence to the vegan diet. Vegan diets showed a statistically significant protective association with prostate cancer risk (HR: 0.65; 95% CI: 0.49, 0.85). After stratifying by race, the statistically significant association with a vegan diet remained only for the whites (HR: 0.63; 95% CI: 0.46, 0.86), but the multivariate HR for black vegans showed a similar but nonsignificant point estimate (HR: 0.69; 95% CI: 0.41, 1.18). CONCLUSION Vegan diets may confer a lower risk of prostate cancer. This lower estimated risk is seen in both white and black vegan subjects, although in the latter, the CI is wider and includes the null.

The Association between Ambient Fine Particulate Air Pollution and Lung Cancer Incidence: Results from the AHSMOG-2 Study.

Background: There is a positive association between ambient fine particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5) and incidence and mortality of lung cancer (LC), but few studies have assessed the relationship between ambient PM2.5 and LC among never smokers. Objectives: We assessed the association between PM2.5 and risk of LC using the Adventist Health and Smog Study-2 (AHSMOG-2), a cohort of health conscious nonsmokers where 81% have never smoked. Methods: A total of 80,285 AHSMOG-2 participants were followed for an average of 7.5 years with respect to incident LC identified through linkage with U.S. state cancer registries. Estimates of ambient air pollution levels at participants’ residences were obtained for 2000 and 2001, the years immediately prior to the start of the study. Results: A total of 250 incident LC cases occurred during 598,927 person-years of follow-up. For each 10-μg/m3 increment in PM2.5, adjusted hazard ratio (HR) with 95% confidence interval (CI) for LC incidence was 1.43 (95% CI: 1.11, 1.84) in the two-pollutant multivariable model with ozone. Among those who spent > 1 hr/day outdoors or who had lived 5 or more years at their enrollment address, the HR was 1.68 (95% CI: 1.28, 2.22) and 1.54 (95% CI: 1.17, 2.04), respectively. Conclusion: Increased risk estimates of LC were observed for each 10-μg/m3 increment in ambient PM2.5 concentration. The estimate was higher among those with longer residence at enrollment address and those who spent > 1 hr/day outdoors. Citation: Gharibvand L, Shavlik D, Ghamsary M, Beeson WL, Soret S, Knutsen R, Knutsen SF. 2017. The association between ambient fine particulate air pollution and lung cancer incidence: results from the AHSMOG-2 study. Environ Health Perspect 125:378–384; http://dx.doi.org/10.1289/EHP124Citation: Gharibvand L, Shavlik D, Ghamsary M, Beeson WL, Soret S, Knutsen R, Knutsen SF. 2017. The association between ambient fine particulate air pollution and lung cancer incidence: results from the AHSMOG-2 study. Environ Health Perspect 125:378–384; http://dx.doi.org/10.1289/EHP124

Legumes and meat analogues consumption are associated with hip fracture risk independently of meat intake among Caucasian men and women: the Adventist Health Study-2

OBJECTIVE In contrast to non-vegetarians, vegetarians consume more legumes and meat analogues as sources of protein to substitute for meat intake. The present study aimed to assess the association between foods with high protein content (legumes, meat, meat analogues) by dietary pattern (vegetarians, non-vegetarians) and hip fracture incidence, adjusted for selected lifestyle factors. DESIGN A prospective cohort of Adventist Health Study-2 (AHS-2) enrollees who completed a comprehensive lifestyle and dietary questionnaire between 2002 and 2007. SETTING Every two years after enrolment, a short questionnaire on hospitalizations and selected disease outcomes including hip fractures was sent to these members. SUBJECTS Respondents (n 33,208) to a baseline and a follow-up questionnaire. RESULTS In a multivariable model, legumes intake of once daily or more reduced the risk of hip fracture by 64% (hazard ratio = 0·36, 95% CI 0·21, 0·61) compared with those with legumes intake of less than once weekly. Similarly, meat intake of four or more times weekly was associated with a 40% reduced risk of hip fracture (hazard ratio = 0·60, 95% CI 0·41, 0·87) compared with those whose meat intake was less than once weekly. Furthermore, consumption of meat analogues once daily or more was associated with a 49 % reduced risk of hip fracture (hazard ratio = 0·51, 95% CI 0·27, 0·98) compared with an intake of less than once weekly. CONCLUSIONS Hip fracture incidence was inversely associated with legumes intake and, to a lesser extent, meat intake, after accounting for other food groups and important covariates. Similarly, a high intake of meat analogues was associated with a significantly reduced risk of hip fracture.

Outcomes of multimodality therapies for patients with stage II or III rectal cancer in California, 1994-2009.

BACKGROUND: Perioperative chemoradiotherapy is being used for the treatment of locally advanced rectal cancer to improve survival and reduce recurrence. Although several studies have prompted these changes, the survival benefits of additional chemoradiotherapy have not been adequately tested in a large-scale, population-based setting. OBJECTIVE: The purpose of this study was to evaluate survival differences between perioperative chemoradiotherapy and surgery alone for the treatment of rectal cancer. DESIGN:  This was a nonconcurrent cohort study of patients treated for rectal cancer stages II and III between 1994 and 2009. SETTING: The study was conducted through the California Cancer Registry. PATIENTS: Eligible patients were those with rectal cancer stage II or III who received either radical surgery alone (N = 2988) or perioperative chemoradiotherapy (N = 8852) during the study period. MAIN OUTCOME MEASURES: Cox proportional hazards regression was used to assess the risk of mortality associated with perioperative chemoradiotherapy versus surgery alone, adjusting for age, sex, race/ethnicity, socioeconomic status, tumor stage, month/year of surgery, and hospital factors. RESULTS: In multivariable binomial log-linear regression, the adjusted prevalence ratio (PR) for receiving perioperative chemoradiotherapy was lower among patients in the older age groups, especially among those ≥75 years of age (PR = 0.52 [95% CI, 0.49–0.55]), and increased monotonically from lowest (PR = 0.92 [95% CI, 0.89–0.95]) to highest socioeconomic status group (referent). Multivariable Cox proportional hazards regression analysis, adjusting for demographic factors, tumor stage, and hospital identification number, showed that perioperative chemoradiotherapy, relative to surgery alone, was associated with lower mortality during the entire study period, with survival benefit increasing over time (1994–1997: HR = 0.76 [95% CI, 0.66–0.88]; 1998–2001: HR = 0.71 [95% CI, 0.64–0.79]; 2002–2005: HR = 0.63 [95% CI, 0.55–0.71]; 2006–2008: HR = 0.47 [95% CI, 0.39–0.56]). LIMITATIONS: No information was available on comorbidities or specific surgeon factors, which could contribute to survival differences. CONCLUSIONS: Perioperative chemoradiotherapy, compared with surgery alone, was associated with significantly improved survival during the entire study period, with increasing benefit among those treated during the latter years of our studied time period. (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A120)

Non-sedentary Lifestyle Can Reduce Hip Fracture Risk among Older Caucasians Adults: The Adventist Health Study-2.

Aims The beneficial effect of physical activity on reducing hip fracture risk has been supported in many previous studies. The present cohort study explores the relationship between total daily physical activity expressed as MET-hour/day and hip fracture risk among men over 50 years of age and postmenopausal women (n=22,836). Methodology Associations between self-reported hip fracture incidence and total daily physical activity and selected lifestyle factors were assessed using Cox proportional hazard regression. Results In gender-specific multivariable models, total activity above average (≥ 51 MET-hours per day for men, ≥ 48 MET-hours per day for women) compared to those with sedentary lifestyle (< 40 MET-hours per day) reduced the risk of hip fracture by 60% among men (HR=0.40, 95%CI: 0.23–0.70) (Ptrend=0.002) and 48% among women (HR=0.52, 95%CI: 0.32–0.84) (Ptrend=0.01). Conclusion Our findings suggest that a moderate level of physical activity and avoiding a sedentary lifestyle can reduce the risk of hip fracture among the elderly.