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Gilad Twig,
Avi Livneh,
Asaf Vivante,
Arnon Afek,
Ari Shamiss,
Estela Derazne,
Dorit Tzur,
Ilan Ben-Zvi, Amir Tirosh,
Micha Barchana,
Tamy Shohat,
Eliezer Golan,
Howard Amital
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ABSTRACT: 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 8.73/10(4) versus 4.32/10(4) 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.
Annals of the rheumatic diseases 03/2013; · 8.11 Impact Factor
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ABSTRACT: BACKGROUND The relationship between adolescent body mass index (BMI) and future risk for end-stage renal disease (ESRD) is not fully understood, nor is it known the extent to which this association is limited to diabetic ESRD. We evaluated the association between BMI in adolescence and the risk for all-cause, diabetic, and nondiabetic ESRD. METHODS Medical data about 1 194 704 adolescents aged 17 years who had been examined for fitness for military service between January 1, 1967, and December 31, 1997, were linked to the Israeli ESRD registry in this nationwide population-based retrospective cohort study. Incident cases of treated ESRD between January 1, 1980, and May 31, 2010, were included. Cox proportional hazards models were used to estimate the hazard ratio (HR) for treated ESRD among study participants for their BMI at age 17 years, defined in accord with the US Centers for Disease Control and Prevention BMI for age and sex classification. RESULTS During 30 478 675 follow-up person-years (mean [SD], 25.51 [8.77] person-years), 874 participants (713 male and 161 female) developed treated ESRD, for an overall incidence rate of 2.87 cases per 100 000 person-years. Compared with adolescents of normal weight, overweight adolescents (85th to 95th percentiles of BMI) and obese adolescents (≥95th percentile of BMI) had an increased future risk for treated ESRD, with incidence rates of 6.08 and 13.40 cases per 100 000 person-years, respectively. In a multivariate model adjusted for sex, country of origin, systolic blood pressure, and period of enrollment in the study, overweight was associated with an HR of 3.00 (95% CI, 2.50-3.60) and obesity with an HR of 6.89 (95% CI, 5.52-8.59) for all-cause treated ESRD. Overweight (HR, 5.96; 95% CI, 4.41-8.06) and obesity (HR, 19.37; 95% CI, 14.13-26.55) were strong and independent risk factors for diabetic ESRD. Positive associations of overweight (HR, 2.17; 95% CI, 1.71-2.74) and obesity (HR, 3.41; 95% CI, 2.42-4.79) with nondiabetic ESRD were also documented. CONCLUSIONS Overweight and obesity in adolescents were associated with significantly increased risk for all-cause treated ESRD during a 25-year period. Elevated BMI constitutes a substantial risk factor for diabetic and nondiabetic ESRD.
Archives of internal medicine 10/2012; · 11.46 Impact Factor
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ABSTRACT: 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 METHODSWBC 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/mm(3). Participants were periodically screened for diabetes during a mean follow-up of 7.5 years.RESULTSDuring 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/mm(3) (P = 0.046). When grouped in quintiles, a baseline WBC count above 6,900 cells/mm(3) 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/mm(3)). 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).CONCLUSIONSWBC 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.
Diabetes care 09/2012; · 8.09 Impact Factor
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ABSTRACT: The ability to reliably identify patients with new hypocortisolemia acutely following pituitary surgery is critical. We aimed to quantify the postoperative cortisol stress response following selective transsphenoidal adenomectomy, as a marker for postoperative preservation of functional pituitary gland. Records of 208 patients undergoing transsphenoidal operations for pituitary lesions were reviewed. Patients with Cushing's Disease, preoperative adrenal insufficiency, and those receiving intraoperative steroids were excluded. To quantify the postoperative stress response, the ∆ cortisol index was defined as the postoperative day (POD) 1 morning cortisol minus the preoperative morning cortisol level. The incidence of new hypocortisolemia requiring glucocorticoid replacement upon hospital discharge was also recorded. Fifty-two patients met inclusion criteria. The mean preoperative, POD1, and POD2 cortisol levels were 16.5, 29.2, and 21.8 μg/dL, respectively. Morning fasting cortisol levels on POD1 ranged from 4.2 to 73.0 μg/dL. The ∆ cortisol index ranged from -19.0 to +56.2 (mean +12.7 μg/dL). Five patients (9.6 %) developed new hypocortisolemia on POD 1-3 requiring glucocorticoid replacement; only one required long-term replacement. The mean ∆ cortisol in patients requiring postoperative glucocorticoids was -2.8 μg/dL, compared with +14.4 μg/dL in patients without evidence of adrenal insufficiency (p = 0.005). Of the 32 patients (61.5 %) with a ∆cortisol >25 μg/dL, none developed postoperative adrenal insufficiency. The postoperative cortisol stress response, as quantified by the ∆ cortisol index, holds potential as a novel and complimentary screening method to predict preservation of normal pituitary function and acute development of new ACTH deficiency following transsphenoidal pituitary surgery.
Pituitary 08/2012; · 1.83 Impact Factor
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ABSTRACT: Subclinical thyroid dysfunction is associated with increased mortality and cardiovascular risk. It is unknown whether this association remains within normal thyroid function range.
The study was conducted using the computerized database of the Sharon-Shomron district of Clalit Health services. Included were subjects aged ≥40 years with normal thyroid function. Patients with a history of thyroid or cardiovascular diseases or diabetes were excluded. The primary end points were all-cause mortality and the need for coronary revascularization with either percutaneous coronary intervention or coronary artery bypass grafting.
The 42,149 participants were stratified into 3 groups of equal thyrotropin intervals (0.35-1.6, 1.7-2.9, and 3-4.2 mIU/L). During a mean follow-up of 4.5±2.1 years, 4239 (10.1%) participants died and 1575 (3.7%) underwent coronary revascularization. For both women and men, the lowest mortality rates were observed in the intermediate thyrotropin group. Nevertheless, only for the low thyrotropin group, mortality risk remained significantly higher as compared with the intermediate thyrotropin group, even following multivariate model adjusted for the conventional cardiovascular risk factors, in both women (odds ratio 1.22; 95% confidence interval, 1.09-1.36 for the low thyrotropin group, compared with the intermediate group) and men (odds ratio 1.14; 95% confidence interval, 1.01-1.3 for the low thyrotropin group, compared with the intermediate group). There was no significant difference in the need for coronary revascularization among the 3 thyrotropin groups in both men and women.
Low thyrotropin level within the reference range is associated with increased risk for all-cause mortality.
The American journal of medicine 05/2012; 125(8):826.e7-12. · 4.47 Impact Factor
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ABSTRACT: The association between white blood cell (WBC) count and coronary artery disease (CAD) is unknown in young adults. Our objective was to assess the association between WBC count and its changes over time with CAD incidence in the Metabolic, Life-style and Nutrition Assessment in Young adults (MELANY) study, a cohort of Israeli army personnel.
29,120 apparently healthy young men (mean age; 31.2±5.5 years) with a normal baseline WBC count (3,000-12,000 cells/mm(3)) were followed during a mean follow up of 7.5±3.8 years for incidence of CAD. Participants were screened every 3-5 years using a stress test, and CAD was confirmed by coronary angiography. In a multivariate model adjusted for age, body mass index (BMI), LDL- and HDL-cholesterol, blood pressure, family history of CAD, physical activity, diabetes, triglycerides and smoking status, WBC levels (divided to quintiles) above 6,900 cells/mm(3) (quintile 4) were associated with a 2.17-fold increase (95%CI = 1.18-3.97) in the risk for CAD as compared with men in quintile 1 (WBC≤5,400 cells/mm(3)). When modeled as a continuous variable, a WBC increment of 1000 cells/mm(3) was associated with a 17.4% increase in CAD risk (HR 1.174; 95%CI = 1.067-1.290, p = 0.001). A decrease in the WBC level (within the normal range) during the follow-up period was associated with increased physical activity and decreased triglyceride levels as well as with reduced incidence of CAD.
WBC count is an independent risk factor for CAD in young adults at values well within the normal range. WBC count may assist in detecting subgroups of young men at either low or high risk for progression to CAD.
PLoS ONE 01/2012; 7(10):e47183. · 4.09 Impact Factor
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ABSTRACT: To determine how changes in lipids, liver enzymes, and inflammatory and glycemia markers intercorrelate during prolonged dietary intervention in obese participants with or without type 2 diabetes (T2D).
We examined the dynamics and intercorrelations among changes in biomarkers during the 2-y Dietary Intervention Randomized Controlled Trial (DIRECT) in 322 participants (including 46 with T2D; 52 y of age, body mass index 31 kg/m(2)) throughout rapid weight loss (0-6 mo) and weight-maintenance/regain (7-24 mo) phases.
The 2-y increase of high-density lipoprotein cholesterol was greater in participants with T2D (+9.41 versus+6.57 mg/dL, P < 0.05), although they tended to have smaller waist circumferences (-2.1 versus -4.0 cm, P = 0.08). In models adjusted for age, sex, and weight loss, the 2-year decrease of triacylglycerols was associated with increases of low-density and high-density lipoprotein cholesterol. An increase of apolipoprotein A1 was associated with a decrease in high-sensitive C-reactive protein (P < 0.05 for all comparisons). Exclusively in participants with T2D, the 2-year decrease in triacylglycerols was further correlated with decreases in apolipoprotein B100 and liver enzymes, and a decrease in fasting glucose correlated with decreases in low-density lipoprotein cholesterol, apolipoprotein B100, and alanine aminotransferase (P < 0.05 for all comparisons). In the entire group, multivariate models adjusted for age, sex, intervention group, and 6-mo weight loss identified decreased high-sensitive C-reactive protein at 6 mo as an exclusive predictor of a greater decrease in triacylglycerols (β = 0.154, P = 0.008) and a greater increase in high-density lipoprotein cholesterol (β = -0.452, P = 0.005) during the subsequent 18 mo.
Long-term dietary intervention induces a flow of changes within biomarkers and the cross-talk is likely to be stronger in T2D. A decrease in systemic inflammation during the weight-loss phase may predict greater long-term improvement in lipids (www.ClinicalTrials.gov, identifier NCT00160108).
Nutrition 08/2011; 28(2):131-7. · 3.03 Impact Factor
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Amir Tirosh,
Iris Shai,
Arnon Afek,
Gal Dubnov-Raz,
Nir Ayalon,
Barak Gordon,
Estela Derazne,
Dorit Tzur,
Ari Shamis,
Shlomo Vinker,
Assaf Rudich
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ABSTRACT: The association of body-mass index (BMI) from adolescence to adulthood with obesity-related diseases in young adults has not been completely delineated.
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.
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).
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.).
New England Journal of Medicine 04/2011; 364(14):1315-25. · 53.30 Impact Factor
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ABSTRACT: Stress stimuli such as tumor necrosis factor (TNF) have been shown to induce insulin receptor substrate (IRS)-1 serine phosphorylation and insulin resistance by transactivation of ErbB receptors. We aimed at elucidating the potential role of p38 mitogen-activated protein kinase (p38MAPK) in mediating stress-induced ErbB receptors activation.
p38MAPK effect on ErbBs transactivation and insulin signaling was assessed in Fao or HepG2 cells, exposed to stress stimuli, and on metabolic parameters in ob/ob and C57/BL6 mice.
High-fat diet-fed mice and ob/ob mice exhibited elevated hepatic p38MAPK activation associated with glucose intolerance and hyperinsulinemia. Liver expression of dominant-negative (DN)-p38MAPKα in ob/ob mice reduced fasting insulin levels and improved glucose tolerance, whereas C57/BL6 mice overexpressing wild-type p38MAPKα exhibited enhanced IRS-1 serine phosphorylation and reduced insulin-stimulated IRS-1 tyrosine phosphorylation. Fao or HepG2 cells exposed to TNF, anisomycin, or sphingomyelinase demonstrated rapid transactivation of ErbB receptors leading to PI3-kinase/Akt activation and IRS-1 serine phosphorylation. p38MAPK inhibition either by SB203580, by small interfering RNA, or by DN-p38MAPKα decreased ErbB receptors transactivation and IRS-1 serine phosphorylation and partially restored insulin-stimulated IRS-1 tyrosine phosphorylation. When cells were incubated with specific ErbB receptors antagonists or in cells lacking ErbB receptors, anisomycin- and TNF-induced IRS-1 serine phosphorylation was attenuated, despite intact p38MAPK activation. The stress-induced p38MAPK activation leading to ErbB receptors transactivation was associated with intracellular reactive oxygen species generation and was attenuated by treatment with antioxidants.
Hepatic p38MAPK is activated following various stress stimuli. This event is upstream to ErbB receptors transactivation and plays an important role in stress-induced IRS-1 serine phosphorylation and insulin resistance.
Diabetes 03/2011; 60(4):1134-45. · 8.29 Impact Factor
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ABSTRACT: Adiponectin receptor-1 (AdipoR1) expression in skeletal muscle has been suggested to play an important role in insulin resistance and diabetes. We aimed at evaluating the presence of novel AdiopR1 splice variants in human muscle and their regulation under physiological and pathophysiological states.
AdipoR1 5'UTR mRNA transcripts, predicted from bioinformatics data, were evaluated in fetal and adult human tissues. Expression and function of the identified transcripts were assessed in cultured human skeletal muscle cells and in muscle biopsies obtained from individuals with normal glucose tolerance (NGT) and type 2 diabetes (n = 49).
Screening of potential AdipoR1 5'UTR splice variants revealed a novel highly abundant muscle transcript (R1T3) in addition to the previously described transcript (R1T1). Unlike R1T1, R1T3 expression was significantly increased during fetal development and myogenesis, paralleled with increased AdipoR1 protein expression. The 5'UTR of R1T3 was found to contain upstream open reading frames that repress translation of downstream coding sequences. Conversely, AdipoR1 3'UTR was associated with enhanced translation efficiency during myoblast-myotube differentiation. A marked reduction in muscle expression of R1T3, R1T1, and R1T3-to-R1T1 ratio was observed in individuals with type 2 diabetes compared with expression levels of NGT subjects, paralleled with decreased expression of the differentiation marker myogenin. Among NGT subjects, R1T3 expression was positively correlated with insulin sensitivity.
These results indicate that AdipoR1 receptor expression in human skeletal muscle is subjected to posttranscriptional regulation, including alternative splicing and translational control. These mechanisms play an important role during myogenesis and may be important for whole-body insulin sensitivity.
Diabetes 02/2011; 60(3):936-46. · 8.29 Impact Factor
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ABSTRACT: Several studies have reported an association between idiopathic intracranial hypertension (IIH) and deficits of the hypothalamic-pituitary-adrenal (HPA) axis.
A 33-yr-old woman with Cushing's disease underwent successful surgical resection of a pituitary adenoma and developed IIH 11 months later after inadvertent withdrawal of oral glucocorticoids.
A review of the literature was conducted to identify previous studies pertaining to IIH in association with neuroendocrine disease, focusing on reports related to HPA axis dysfunction.
A number of patients developing IIH due to a relative deficiency in glucocorticoids, after surgical or medical management for Cushing's disease, withdrawal from glucocorticoid replacement, or as an initial presentation of Addison's disease, have been reported. Hypotheses regarding the underlying pathophysiology of IIH in this context and, in particular, the role of cortisol and its relationship to other neuroendocrine and inflammatory mediators that may regulate the homeostasis of cerebrospinal fluid production and absorption are reviewed.
In a subset of patients, dysfunction of the HPA axis appears to play a role in the development of IIH. Hormonal control of cerebrospinal fluid production and absorption may be regulated by inflammatory mediators and the enzyme 11ß-hydroxysteroid dehydrogenase type 1. Further study of neuroendocrine markers in the serum and cerebrospinal fluid may be an avenue for further research in IIH.
The Journal of clinical endocrinology and metabolism 11/2010; 95(11):4850-4. · 6.50 Impact Factor
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ABSTRACT: Key components of the metabolic syndrome (MetS), ie, obesity and insulin resistance, are associated with increased aldosterone production and mineralocorticoid receptor (MR) activation. Both MetS and hyperaldosteronism are proinflammatory and pro-oxidative states associated with cardiovascular disease. This review discusses emerging data that MR activation may contribute to abnormalities seen in MetS. In view of these data, MR antagonists may be beneficial in MetS, not only by controlling hypertension but also by reversing inflammation, oxidative stress, and defective insulin signaling at the cellular-molecular level. Clinical trials have demonstrated benefits of MR antagonists in heart failure, hypertension, and diabetic nephropathy, but additional trials are needed to demonstrate the clinical significance of MR blockade in MetS.
Current Hypertension Reports 08/2010; 12(4):252-7. · 2.50 Impact Factor
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Amir Tirosh,
Arnon Afek,
Assaf Rudich,
Ruth Percik,
Barak Gordon,
Nir Ayalon,
Estela Derazne,
Dorit Tzur,
Daphna Gershnabel,
Ehud Grossman,
Avraham Karasik,
Ari Shamiss,
Iris Shai
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ABSTRACT: 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.
Hypertension 08/2010; 56(2):203-9. · 6.21 Impact Factor
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ABSTRACT: The finding in some recent studies that the prevalence of asthma is higher in poor populations contradicts the hygiene theory, which claims that improved quality of life removes protective factors that prevent atopy.
To determine whether socioeconomic status (SES) is associated with the prevalence of asthma in adolescents in Israel.
The study sample consisted of 159,243 consecutive 17-year-old military recruits examined in the Israel Defense Forces. Relevant medical data were collected from the army's computerized database. The SES of the recruits was assessed according to the socioeconomic grade (by quintiles) assigned to their city or town of residence by the Israel Central Bureau of Statistics and by the number of children in the family.
Asthma was documented in 8.5% of the male recruits and in 6.7% of the female recruits. The prevalence of asthma increased with an increase in socioeconomic grade, from 3.7% for the lowest quintile to 8.8% for the highest (P < .001). Separate analysis of individuals from the Tel Aviv area showed that the prevalence of asthma ranged from 3.4% to 13.7% from the lowest to the highest socioeconomic quintiles (P < .001). In Israel, having a higher number of children in the family is associated with lower SES. There was an inverse relationship between number of children in the family and the prevalence of asthma: 8.7% in families with 1 or 2 children and 1.9% in families with 9 or more children.
High SES is associated with a relatively high prevalence of asthma in adolescents in Israel.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 06/2010; 104(6):490-5. · 2.83 Impact Factor
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Iris Shai,
J David Spence,
Dan Schwarzfuchs,
Yaakov Henkin,
Grace Parraga,
Assaf Rudich,
Aaron Fenster,
Christiane Mallett,
Noah Liel-Cohen, Amir Tirosh,
Arkady Bolotin,
Joachim Thiery,
Georg Martin Fiedler,
Matthias Blüher,
Michael Stumvoll,
Meir J Stampfer
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ABSTRACT: It is currently unknown whether dietary weight loss interventions can induce regression of carotid atherosclerosis.
In a 2-year Dietary Intervention Randomized Controlled Trial-Carotid (DIRECT-Carotid) study, participants were randomized to low-fat, Mediterranean, or low-carbohydrate diets and were followed for changes in carotid artery intima-media thickness, measured with standard B-mode ultrasound, and carotid vessel wall volume (VWV), measured with carotid 3D ultrasound. Of 140 complete images of participants (aged 51 years; body mass index, 30 kg/m(2); 88% men), higher baseline carotid VWV was associated with increased intima-media thickness, age, male sex, baseline weight, blood pressure, and insulin levels (P<0.05 for all). After 2 years of dietary intervention, we observed a significant 5% regression in mean carotid VWV (-58.1 mm(3;) 95% confidence interval, -81.0 to -35.1 mm(3); P<0.001), with no differences in the low-fat, Mediterranean, or low-carbohydrate groups (-60.69 mm(3), -37.69 mm(3), -84.33 mm(3), respectively; P=0.28). Mean change in intima-media thickness was -1.1% (P=0.18). A reduction in the ratio of apolipoprotein B(100) to apolipoprotein A1 was observed in the low-carbohydrate compared with the low-fat group (P=0.001). Participants who exhibited carotid VWV regression (mean decrease, -128.0 mm(3); 95% confidence interval, -148.1 to -107.9 mm(3)) compared with participants who exhibited progression (mean increase, +89.6 mm(3); 95% confidence interval, +66.6 to +112.6 mm(3)) had achieved greater weight loss (-5.3 versus -3.2 kg; P=0.03), greater decreases in systolic blood pressure (-6.8 versus -1.1 mm Hg; P=0.009) and total homocysteine (-0.06 versus +1.44 mumol/L; P=0.04), and a higher increase of apolipoprotein A1 (+0.05 versus -0.00 g/L; P=0.06). In multivariate regression models, only the decrease in systolic blood pressure remained a significant independent modifiable predictor of subsequent greater regression in both carotid VWV (beta=0.23; P=0.01) and intima-media thickness (beta=0.28; P=0.008) levels.
Two-year weight loss diets can induce a significant regression of measurable carotid VWV. The effect is similar in low-fat, Mediterranean, or low-carbohydrate strategies and appears to be mediated mainly by the weight loss-induced decline in blood pressure. Clinical Trial Registration- http://www.clinicaltrials.gov. Unique Identifier: NCT00160108.
Circulation 03/2010; 121(10):1200-8. · 14.74 Impact Factor
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ABSTRACT: Family history is one of the main risk factors for cardiovascular disease, especially in the younger population. These individuals, being closely related to young symptomatic patients, are anticipated to have a high rate of risk factors but also to control them aggressively. The aim of the study was to evaluate the association between family history of cardiovascular disease and risk factors that control as well as reduce risk-reducing behavior among young, healthy adults.
Demographic, clinical and lifestyle parameters of career service personnel of the Israeli Defense Forces, who were checked at the staff periodic examination center, were evaluated. Behavioral and clinical parameters of participants, with and without cardiovascular family history, were compared.
The study cohort comprised 41,099 patients (36,236 men and 4863 women). Of those, 3802 men and 628 women with a family history of cardiovascular disease were identified. Male individuals had a higher rate of treatable risk factors like, obesity (P<0.0005), high blood pressure (P<0.0005), high plasma glucose (P<0.0005) and dyslipidemia (P<0.0005) than individuals without a family history. Among the women, the rate of these risk factors was higher than in the control groups but was statistically significant only for obesity, high blood pressure and high glucose levels. Risk-reducing behavior like regular physical activity and nonsmoking status in both the sexes did not differ between the groups.
Members of the young population with a family history of cardiovascular disease is easily identified but remains largely uncontrolled. Special attention and continued education are required to modify their behavioral and medical parameters.
European Journal of Cardiovascular Prevention and Rehabilitation 06/2008; 15(3):325-8. · 2.63 Impact Factor
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ABSTRACT: The association between changes in triglyceride concentrations over time and diabetes is unknown. We assessed whether two triglyceride determinations obtained 5 years apart can predict incident type 2 diabetes.
Triglyceride levels at baseline (time 1) and 5 years later (time 2), followed by subsequent follow-up of 5.5 years, were measured in 13,953 apparently healthy men (age 26-45 years) with triglycerides <300 mg/dl (<3.39 mmol/l).
During 76,742 person-years, 322 cases of diabetes occurred. A multivariate model adjusted for age, BMI, total cholesterol-to-HDL cholesterol ratio, family history of diabetes, fasting glucose, blood pressure, physical activity, and smoking status revealed a continuous independent rise in incident diabetes with increasing time 1 triglyceride levels (P(trend) < 0.001). Men in the lowest tertile of time 1 triglyceride levels who progressed to the highest tertile over follow-up (low-high) exhibited a hazard ratio (HR) of 12.62 (95% CI 3.52-31.34) compared with those remaining in the lowest tertile at both time points (reference group: low-low). Whereas men who were at the top triglyceride level tertile throughout follow-up (high-high) had a HR for diabetes of 7.08 (2.52-14.45), those whose triglyceride level decreased to the lowest tertile (high-low) exhibited a HR of 1.97 (0.67-6.13). Alterations in triglyceride levels during follow-up were associated with changes in BMI, physical activity, and eating breakfast habit (P < 0.05), but remained an independent modifier of diabetes risk even after adjustment for such changes.
Two measurements of fasting triglyceride levels obtained 5 years apart can assist in identifying apparently healthy young men at increased risk for diabetes, independent of traditional risk factors and of associated changes in BMI and lifestyle parameters.
Diabetes care 06/2008; 31(10):2032-7. · 8.09 Impact Factor
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ABSTRACT: AIMS: Although impaired renal function is associated with adverse cardiovascular outcomes, it is unknown whether this association exists in young, healthy adults with normal or mildly impaired renal dysfunction. METHODS AND RESULTS We calculated the baseline creatinine clearance of young males without antecedent diabetes mellitus, coronary artery disease (CAD), or renal dysfunction, and examined their subsequent diagnosis of CAD, defined as coronary artery diameter stenosis of at least 50% and/or myocardial infarction. The 23 964 males, 32.5 +/- 5.9 years old, had a baseline estimated creatinine clearance of 107.9 +/- 0.6 mL min(-1) per 1.73 m(2) (60-150 mL min(-1) per 1.73 m(2)). During a mean follow-up of 3.5 +/- 1.9 years, 77 subjects were diagnosed with CAD. After age adjustment, there was a progressive increase in the risk for CAD as the estimated creatinine clearance decreased [hazard ratio (HR) 4.77, 95% confidence interval 3.22-7.06, P < 0.001 for comparison between the fifth and first quintiles]. This association also persisted after further adjustments for conventional and ancillary risk factors for CAD (HR 2.10, 95% confidence interval 1.40-3.14, P < 0.001). Conclusion Reduced renal function in the normal to mildly impaired range is independently associated with increased risk for CAD among young, healthy males.
European Heart Journal 01/2008; 29(2):198-203. · 10.48 Impact Factor
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ABSTRACT: Current triglyceride levels might be only a weak predictor of risk for coronary heart disease (CHD).
To assess the association between changes over time in fasting triglyceride levels and CHD risk in young adults.
Follow-up study over 5.5 years after 2 measurements of fasting triglycerides 5 years apart.
The Staff Periodic Examination Center of the Israel Defense Forces, Zrifin, Israel.
13,953 apparently healthy, untreated, young men (age 26 to 45 years) with triglyceride levels less than 3.39 mmol/L (<300 mg/dL).
Two triglyceride measurements (at enrollment [time 1] and 5 years later [time 2]), lifestyle variables, and incident cases of angiography-proven CHD.
Within 5.5 years, 158 new cases of CHD were identified. The multivariate model was adjusted for age; family history; fasting glucose; high-density lipoprotein cholesterol; blood pressure; body mass index; and changes between time 1 and time 2 in body mass index, physical activity, smoking status, and habit of eating breakfast. Investigators categorized triglyceride levels according to low, intermediate, and high tertiles (as measured at time 1 and time 2 [expressed as tertile at time 1/tertile at time 2]). The risk for CHD in men with high-tertile triglyceride levels at time 1 changed depending on the tertile at time 2 (hazard ratios, 8.23 [95% CI, 2.50 to 27.13] for high/high, 6.84 [CI, 1.95 to 23.98] for high/intermediate, and 4.90 [CI, 1.01 to 24.55] for high/low, compared with the stable low/low group). The risk for CHD in men with low-tertile levels at time 1 also changed depending on the tertile at time 2 (hazard ratios, 3.81 [CI, 0.96 to 15.31] for low/intermediate and 6.76 [CI, 1.34 to 33.92] for low/high, compared with the stable low/low group).
Participants were healthy and had a low incidence rate of CHD. The study was observational.
Two triglyceride measurements obtained 5 years apart may assist in assessing CHD risk in young men. A decrease in initially elevated triglyceride levels is associated with a decrease in CHD risk compared with stable high triglyceride levels. However, this risk remains higher than in those with persistently low triglyceride levels.
Annals of internal medicine 09/2007; 147(6):377-85. · 16.73 Impact Factor
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ABSTRACT: It is estimated that by 2025, >1.5 billion adults worldwide will be hypertensive. Early identification of the population at risk would lead to improved utilization of preventive measures. We aimed to evaluate whether baseline body mass index (BMI) and blood-pressure (BP) values during adolescence (categorized according to the guidelines of the European Society of Hypertension-European Society of Cardiology) are of use in predicting the development of hypertension in young adulthood.
The study population consisted of 18,513 male regular army personnel who were initially recruited at 16.5 and 19 years of age between 1976 and 1996. The main outcome was the percentage of subjects who developed hypertension (> or =140 systolic and > or =90 diastolic) at ages 26 to 45 years.
At baseline, BP categories were: optimal, 5961 (32.2%); normal, 7998 (43.2%); and high normal, 4554 (24.6%). Moreover, 1377 (7.4%) were overweight (BMI 25-30 kg/m(2)), and 199 (1.1%) were obese (BMI >30 kg/m(2)). At follow-up, 2277 (12.3%) subjects developed hypertension. The percentages progressing to hypertension were 9.46%, 11.99%, and 16.56% for optimal, normal, and high-normal categories, respectively (P < .01). Odds ratios (OR) for the development of hypertension in the normal and high-normal categories versus optimal were 1.30 (95% confidence interval [CI], 1.22-1.39) and 1.79 (95% CI, 1.67-1.93), respectively, adjusted for age and BMI. The ORs for hypertension in overweight and obese versus normal BMI were 1.75 (95% CI, 1.66-1.86) and 3.75 (95% CI, 3.45-4.07), adjusted for age and BP. Of 9762 remaining at ideal BMI at follow-up, the percentages progressing to hypertension were 5.3%, 6.4%, and 9.5% for optimal, normal, and high normal (at baseline) (P < .01).
The risk of developing hypertension in young adulthood may be predicted by BP categories and BMI at adolescence.
American Journal of Hypertension 06/2007; 20(6):705-9. · 3.18 Impact Factor
