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Tirosh A.,Harvard University | Tirosh A.,Chaim Sheba Medical Center | Afek A.,Chaim Sheba Medical Center Management | Afek A.,Tel Aviv University | And 16 more authors.

Although prehypertension at adolescence is accepted to indicate increased future risk of hypertension, large-scale/long follow-up studies are required to better understand how adolescent blood pressure (BP) tracks into young adulthood. We studied 23 191 male and 3789 female adolescents from the Metabolic Lifestyle and Nutrition Assessment in Young Adults cohort (mean age: 17.4 years) with BP <140/90 mm Hg at enrollment or categorized by current criteria for pediatric BP and body mass index (BMI) values. Participants were prospectively followed up with repeated BP measurements between ages 25 and 42 years and retrospectively between ages 17 and 25 years for the incidence of hypertension. We identified 3810 new cases of hypertension between ages 17 and 42 years. In survival analyses, the cumulative risk of hypertension between ages 17 and 42 years was 3 to 4 times higher in men than in women. Using Cox regression models adjusted for age, BMI, and stratified by baseline BP, the hazard ratio of hypertension increased gradually across BP groups within the normotensive range at age 17 years, without a discernible threshold effect, reaching a hazard ratio of 2.50 (95% CI: 1.75 to 3.57) for boys and 2.31 (95% CI: 0.71 to 7.60) for girls in the group with BP at 130 to 139/85 to 89 mm Hg. BMI at age 17 years was strongly associated with future risk of hypertension even when adjusted to BP at age 17 years, particularly in boys. Yet, BMI at age 30 years attenuated this association, more evidently in girls. In conclusion, BP at adolescence, even in the low-normotensive range, linearly predicts progression to hypertension in young adulthood. This progression and the apparent interaction between BP at age 17 years and BMI at adolescence and at adulthood are sex dependent. © 2010 American Heart Association, Inc. Source

Tirosh A.,Harvard University | Tirosh A.,Boston University | Tirosh A.,Chaim Sheba Medical Center | Shai I.,Ben - Gurion University of the Negev | And 11 more authors.
New England Journal of Medicine

BACKGROUND: The association of body-mass index (BMI) from adolescence to adulthood with obesity-related diseases in young adults has not been completely delineated. METHODS: We conducted a prospective study in which we followed 37,674 apparently healthy young men for incident angiography-proven coronary heart disease and diabetes through the Staff Periodic Examination Center of the Israeli Army Medical Corps. The height and weight of participants were measured at regular intervals, with the first measurements taken when they were 17 years of age. RESULTS: During approximately 650,000 person-years of follow-up (mean follow-up, 17.4 years), we documented 1173 incident cases of type 2 diabetes and 327 of coronary heart disease. In multivariate models adjusted for age, family history, blood pressure, lifestyle factors, and biomarkers in blood, elevated adolescent BMI (the weight in kilograms divided by the square of the height in meters; mean range for the first through last deciles, 17.3 to 27.6) was a significant predictor of both diabetes (hazard ratio for the highest vs. the lowest decile, 2.76; 95% confidence interval [CI], 2.11 to 3.58) and angiography-proven coronary heart disease (hazard ratio, 5.43; 95% CI, 2.77 to 10.62). Further adjustment for BMI at adulthood completely ablated the association of adolescent BMI with diabetes (hazard ratio, 1.01; 95% CI, 0.75 to 1.37) but not the association with coronary heart disease (hazard ratio, 6.85; 95% CI, 3.30 to 14.21). After adjustment of the BMI values as continuous variables in multivariate models, only elevated BMI in adulthood was significantly associated with diabetes (β = 1.115, P = 0.003; P = 0.89 for interaction). In contrast, elevated BMI in both adolescence (β = 1.355, P = 0.004) and adulthood (β = 1.207, P = 0.03) were independently associated with angiography-proven coronary heart disease (P = 0.048 for interaction). CONCLUSIONS: An elevated BMI in adolescence - one that is well within the range currently considered to be normal - constitutes a substantial risk factor for obesity-related disorders in midlife. Although the risk of diabetes is mainly associated with increased BMI close to the time of diagnosis, the risk of coronary heart disease is associated with an elevated BMI both in adolescence and in adulthood, supporting the hypothesis that the processes causing incident coronary heart disease, particularly atherosclerosis, are more gradual than those resulting in incident diabetes. (Funded by the Chaim Sheba Medical Center and the Israel Defense Forces Medical Corps.) Copyright © 2011 Massachusetts Medical Society. Source

Twig G.,Chaim Sheba Medical Center | Twig G.,Israel Defense Forces | Afek A.,Chaim Sheba Medical Center Management | Afek A.,Tel Aviv University | And 9 more authors.
Diabetes Care

OBJECTIVE-Association between white blood cell (WBC) count and diabetes risk has been recently suggested. We assessed whether WBC count is an independent risk factor for diabetes incidence among young healthy adults. RESEARCH DESIGN AND METHODS-WBC count was measured in 24,897 young (mean age 30.8 ± 5.36 years), normoglycemic men with WBC range of 3,000 to 12,000 cells/ mm3. Participants were periodically screened for diabetes during a mean follow-up of 7.5 years. RESULTS-During 185,354 person-years of follow-up, diabetes was diagnosed in 447 subjects. A multivariate model adjusted for age, BMI, family history of diabetes, physical activity, and fasting glucose and triglyceride levels revealed a 7.6% increase in incident diabetes for every increment of 1,000 cells/mm3 (P = 0.046). When grouped in quintiles, a baseline WBC count above 6,900 cells/mm3 had an independent 52% increase in diabetes risk (hazard ratio 1.52 [95% CI 1.06-2.18]) compared with the lowest quintile (WBC <5,400 cells/mm3). Men at the lowest WBC quintile were protected from diabetes incidence even in the presence of overweight, family history of diabetes, or elevated triglyceride levels. After simultaneous control for risk factors, BMI was the primary contributor of the variation in multivariate models (P < 0.001), followed by age and WBC count (P < 0.001), and family history of diabetes and triglyceride levels (P = 0.12). CONCLUSIONS-WBC count, a commonly used and widely available test, is an independent risk factor for diabetes in young men at values well within the normal range.© 2013 by the American Diabetes Association. Source

Twig G.,Chaim Sheba Medical Center | Twig G.,Israel Defense Forces | Livneh A.,Chaim Sheba Medical Center | Livneh A.,Heller Institute of Medical Research | And 22 more authors.
Annals of the Rheumatic Diseases

Objective: There are limited data on long-term comorbidities and mortality among patients with familial Mediterranean fever (FMF). Our objective was to evaluate comorbidities and death rates among individuals with FMF. Methods: We studied a nationwide, population-based, retrospective cohort of 1225 individuals with FMF (59% men) in a database of 1 244 350 adolescents (16-20 years of age) medically evaluated for military service between 1973 and 1997. This cohort was linked with the national mortality, cancer and end-stage renal disease (ESRD) registries in Israel. Study outcomes were all-cause mortality, occurrence of ESRD and malignancy by the age of 50 years. Results: During 30 years of follow-up, death rates were 8.73/104 versus 4.32/104 person-years in the FMF and control groups, respectively (p=0.002). In a multivariable analysis adjusted for age, birth year, socio-economic status, education, ethnicity and body mass index, FMF was associated with increased mortality in men (HR=1.705 (95% CI 1.059 to 2.745), p=0.028) and women (HR=2.48 (1.032 to 5.992), p=0.042). Renal amyloidosis accounted for 35% and 60% of deaths in men and women, respectively. FMF was not associated with an increased incidence of cancer. Conclusions: FMF is associated with increased all-cause mortality that is likely attributed to reduced colchicine compliance or responsiveness. Individuals with FMF do not have an increased incidence of cancer. These results support the awareness among medical community to decrease the higher than average mortality rate among participants with FMF. Source

Twig G.,Israel Defense Forces | Afek A.,Chaim Sheba Medical Center Management | Afek A.,Tel Aviv University | Shamiss A.,Chaim Sheba Medical Center Management | And 10 more authors.
Journal of Clinical Endocrinology and Metabolism

Context: The consequence of elevated body mass index (BMI) at adolescence on early adulthood mortality rate and on predicted life expectancy is unclear. Objective: The objective of the investigation was to study the relationship between BMI at adolescence and mortality rate as well as the mortality trend over the past 4 decades across the entire BMI range. Design and Setting: The study included a nationwide longitudinal cohort. Participants: A total of 2 159 327 adolescents (59.1% males) born between 1950 and 1993, who were medically evaluated for compulsory military service in Israel, participated in the study. Interventions: Height and weight were measured at age 17 years, and BMI was stratified based on the Centers for Disease Control and Prevention-established percentiles for age and sex. Main Outcome Measure: Incident cases of all-cause mortality before age 50 years were recorded. Cox-proportional hazard models were used to assess mortality rates and its trend overtime. Results: During 43 126 211 person-years of follow-up, 18 530 deaths were recorded. As compared with rates observed in the 25th to 50th BMI percentiles, all-cause mortality continuously increased across BMI range, reaching rates of 8.90/104 and 2.90/104 person-years for men and women with BMI greater than the 97th percentile, respectively. A multivariate analysis adjusted for age, socioeconomic status, education, and ethnicity demonstrated a significant increase in mortality at BMI greater than the 50th percentile (BMI < 20.55 kg/m2) for men and the 85th percentile or greater inwomen(BMI<24.78 kg/m2). During the last 4 decades, a significant decrease in mortality rates was documented in normal-weight participants born between 1970 and 1980 vs those born between 1950 and 1960 (3.60/104 vs 4.99/104 person-years, P > .001). However, no improvement in the survival rate was observed among overweight and obese adolescents during the same time interval. Significant interaction between BMI and birth year was observed (P = .007). Conclusions: BMI at adolescence, within the normal range, is associated with all-cause mortality in adulthood. Mortality rates among overweight and obese adolescents did not improve in the last 40 years, suggesting that preadulthood obesity may attenuate the progressive increase in life expectancy. © 2014 by the Endocrine Society. Source

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