Association of different lipid measures with incident bone fractures: Tehran lipid and glucose study.

OBJECTIVE: To investigate the association between different lipid measures and long-term hospitalization-required incident fracture among Iranian men and women. METHODS: A total of 3309 individuals aged ≥50 years (men = 1598) were included in the study. Multivariate Cox proportional hazard analyses were performed to assess the risk of incident fracture across quintiles, considering first quintile as reference, as well as for 1-standard deviation (SD) increase in each lipid measure, i.e. total cholesterol (TC), triglycerides (TG), low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively), non-HDL-C, and related indices (TG/HDL-C and TC/HDL-C). Covariates included age, body mass index, current smoking, type 2 diabetes mellitus, hypertension, lipid lowering-drugs, and steroid medications (for women). RESULTS: During a median follow-up of 18 years, incident fracture was observed in 201 cases (men = 87). In both gender, no linear association was found between different lipid measures and incident fracture. Among men, only the fourth quartile of TG was associated with lower risk of fracture in the age-adjusted analysis with the hazard ratio (HR) and 95% confidence interval (CI) of [0.45 (0.21-0.95)]. Among women, the age-adjusted HRs and 95% CIs for the second, third, fourth, and fifth quintiles of non-HDL-C were [0.46 (0.25-0.87)], [0.73 (0.42-1.25)], [0.90 (0.54-1.51)], and [0.52 (0.29-0.95)], respectively; the corresponding values in the multivariate model were [0.48 (0.26-0.90)], [0.76 (0.4-1.32)], [0.94 (0.56-1.58)], and [0.52 (0.28-0.95)], respectively. The second quintile of LDL-C was also associated with lower risk for incident fracture in the multivariate analysis [0.53 (0.29-0.98)]. CONCLUSIONS: Among Iranian women, a nonlinear association between non-HDL-C and LDL-C and incident fracture was found as the second and fifth quintile of the former and the second quintile of the latter were associated with about 50% lower risk of fracture. Generally, our findings did not support harmful impact of these lipid measures on incident fracture.

Impact of educational level on incident chronic kidney disease during 13 years of follow-up: a prospective cohort study.

OBJECTIVES: To examine the association between educational level and chronic kidney disease (CKD) among the Iranian population. STUDY DESIGN: This is a prospective cohort study conducted in the framework of the Tehran Lipid and Glucose Study. METHODS: A total of 8173 Iranians (men = 3659) aged ≥20 years were included in the study. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. The association between educational status and CKD was explored using multivariate Cox proportional regression analyses, adjusted for age, gender, current smoking, marital status, body mass index, waist circumference, baseline eGFR, diabetes, hypertension, physical activity, history of cardiovascular diseases and dyslipidaemia. RESULTS: During a median follow-up of 13.14 years, 2609 cases of incident CKD were identified; the corresponding incidence rate was 26.35 (range 25.39-27.34) per 1000 person-years. Compared to low educational level, middle and high educational levels showed lower risks for incident CKD in the crude model [hazard ratio (HR) 0.37 (95% confidence interval {CI} 0.34-0.40) and HR 0.40 (95% CI 0.35-0.45), respectively]; however, these HRs changed direction after further adjustment for age and gender [HR 1.26 (95% CI 1.14-1.39) and HR 1.40 (95% CI 1.22-1.61), respectively]. The increased risk of incident CKD for those at higher educational levels remained significant in the fully adjusted model. In addition, results from the gender stratified analyses were in the same direction as those found among the whole study population (P-value for interaction of gender and education >0.8). CONCLUSIONS: Higher educational levels were associated with incident CKD during more than a decade of follow-up; this finding may be attributed to unhealthy lifestyle behaviours among this population group.

All-cancer incidence in Tehranian adults: more than a decade of follow-up-results from the Tehran Lipid and Glucose Study.

OBJECTIVES: To investigate the incidence rates for different malignancies and assess the risk factors for all-cancer incidence in Tehran. STUDY DESIGN: Cohort study. METHODS: This study consists of 8599 participants aged ≥ 30 years who were free of cancer (3935 men). Cancer diagnosis was based on pathology reports. Sex-stratified crude incidence rates and age-standardized incidence rates (ASRs) using Segi's method were calculated for all-cancers. Multivariate Poisson regression models were used to evaluate associations of potential risk factors, including sex, age, obesity status (body mass index [BMI]: 25-30 kg/m2 as reference), education, smoking status, and diabetes mellitus with the incidence of cancers among the population. Incidence rate ratios (IRRs) with 95% confidence interval (CI) were also reported. RESULTS: During a median follow-up of 13.9 years, there were 130 and 129 incident cancers for men and women, respectively; the corresponding ASRs were 356.1 and 243.6 per 100,000 person-years, respectively. The three most incident cancers among men were gastrointestinal (GI) (ASR = 127.5), hematopoietic (ASR = 99.5), and reproductive system malignancies (ASR = 46.3). The most common incident cancers in women were breast cancer (ASR = 92.1), GI (ASR = 65.4), and reproductive system malignancies (ASR = 16.8). Among risk factors for cancer incidence, age (IRR [95% CI]: 1.05 [1.03-1.06]) and having a BMI < 25 kg/m2 (IRR [95% CI]: 1.38 [1.01-1.90]) had a statistically significant association with incident cancer. CONCLUSIONS: The high rates of cancers in Tehran during more than a decade of follow-up calls for a need to define risk factors as well as to implement programs for early screening.

Different combinations of glucose tolerance and blood pressure status and incident cardiovascular disease and all-cause mortality events.

The purpose of this study was to evaluate the effect of combinations of blood pressure and glucose tolerance status on cardiovascular and all-cause mortality. A total of 7619 participants aged ⩾30 years old were stratified to nine categories as follows: (1) normotension (NTN) and normal glucose tolerance (NGT) (reference group), (2) NTN and pre-diabetes mellitus (pre-DM), (3) NTN and DM, (4) pre-hypertension (pre-HTN) and NGT, (5) pre-HTN and pre-DM, (6) pre-HTN and DM, (7) HTN and NGT, (8) HTN and pre-DM and (9) HTN and DM. Cox proportional hazards were applied to calculate the multivariate hazard ratios (HRs) of different groups for outcomes. For all-cause mortality outcomes, prevalent cardiovascular disease (CVD) was also adjusted. In a median follow-up of 11.3 years, 696 CVD and 412 all-cause mortality events occurred. Among the population free from CVD at baseline (n=7249), presence of HTN was associated with increased risk of CVD, regardless of glucose tolerance status with HRs of 1.97 (95% confidence interval (CI), 1.49-2.61), 2.25 (1.68-3.02) and 3.16 (2.28-4.37) for phenotypes of HTN and NGT, HTN and pre-DM and HTN and DM for CVD, respectively; corresponding HRs for all-cause mortality were 1.65 (95% CI, 1.15-2.37), 1.69 (1.15-2.49) and 2.73 (1.80-4.14), respectively. Phenotypes of NTN and pre-DM (1.48; 1.03-2.14) and NTN and DM (2.04; 1.06-3.92) were also associated with CVD and all-cause mortality, respectively. HTN was significantly associated with CVD/mortality events, regardless of glucose tolerance status. Blood pressure <120/80 mm Hg among pre-diabetic/diabetic population, not on antihypertensive medications, was generally associated with worse outcomes.

Blood pressure and cardiovascular morbidity risk in type 2 diabetes with hypertension over a decade of follow-up: evidence for J-shaped phenomenon.

There is still debate on whether the relationship between blood pressure (BP) and risk of cardiovascular diseases (CVD) in patients with type 2 diabetes (T2D) is linear or not. Since these cardio-metabolic disturbances share interrelated complex pathogenic mechanisms, we aimed to assess the relationship of baseline systolic (SBP)/diastolic pressures with CVD and coronary heart disease (CHD) events in a cohort of Iranians with T2D during a median follow-up of 8.8 years. Of all 1009 eligible participants with T2D with a mean (s.d.) age of 54.4 (11.6) years and free of CVD at baseline, we primarily focused on 260 participants undergoing anti-hypertensive treatment. Multivariate Cox proportional hazard models were used to evaluate hazard ratios (HR) of BP categories for CVD and CHD events. Also, multivariable regression modelling was applied to obtain their risk curve. We detected a J-shaped phenomenon between the continuous baseline BP and risk of CVD events. Considering 130⩽SBP<140 mm Hg as reference, a SBP ⩾140 mm Hg was associated with increased CVD (HR [95% confidence interval (CI)]: 2.43 [1.23-4.82]) and CHD (HR [95% CI]: 2.05 [1.02-4.13]) risk. However, a SBP⩽120 mm Hg in those with drug-treated hypertension also showed higher risk for CVD (HR [95% CI]: 2.80 [1.24-6.34]) and CHD events (HR [95% CI]: 2.39 [1.03-5.57]). Our findings revealed that the risk for macrovascular morbidity events was inversely associated with BP reduction below the level of 120/80 mm Hg for those with diabetes. People with diabetes might benefit from a BP management to a moderate range of 120/80-140/90 mm Hg for CVD risk reduction.

Sex-specific incidence rates and risk factors of insulin resistance and ß-cell dysfunction: a decade follow-up in a Middle Eastern population.

AIMS: To examine the incidence of and risk factors for insulin resistance and ß-cell dysfunction in a representative Iranian population over a median follow-up of 9.2 years. METHODS: In total, 3662 people (1528 men) without known diabetes with a baseline homeostasis model assessment of insulin resistance (HOMA-IR) level < 75th percentile and, when ß-cell dysfunction was the outcome of interest, 3664 people (1530 men) with a homeostasis model assessment of ß-cell function (HOMA-ß) level ≥ 25th percentile were included in the study (HOMA-IR < 2.20 and HOMA-ß ≥ 64.3 among men, and HOMA-IR < 2.39 and HOMA-ß ≥ 81.7 among women). RESULTS: The incidence rates of insulin resistance and ß-cell dysfunction were 56.3 and 33.6/1000 person-years among men and 48.6 and 50.3/1000 person-years among women, respectively. Applying multivariable Cox regression in both sexes, fasting insulin, triglyceride/HDL cholesterol ratio and lower education were positive predictors of insulin resistance, whereas age was a negative predictor. Moreover, fasting plasma glucose, waist-to-height ratio, wrist circumference and lower hip circumference were significantly associated with incident insulin resistance only among women (all P < 0.05). Considering ß-cell dysfunction in both sexes, age and fasting plasma glucose increased the risk, whereas 2-h post-challenge plasma glucose was a positive predictor only among men, and waist-to-height ratio and triglyceride/HDL cholesterol ratio were negative predictors only among women (all P < 0.05). CONCLUSIONS: Modifiable risk factors are related to the incidence of insulin resistance and ß-cell dysfunction, which can be prevented with proper strategies although the difference between men and women should be taken into account.

Pre-diabetes tsunami: incidence rates and risk factors of pre-diabetes and its different phenotypes over 9 years of follow-up.

AIMS: To investigate the incidence of pre-diabetes and its different phenotypes and the related risk factors during 9 years of follow-up. METHODS: A total of 5879 people (2597 men and 3282 women) aged ≥ 20 years, free of diabetes and pre-diabetes, took part in the study. Multivariable Cox proportional hazard models were used to evaluate hazard ratios (HR) and 95% confidence intervals (CI) for all potential risk factors. RESULTS: Overall, 853 men and 902 women developed pre-diabetes. Incidence rates of pre-diabetes were 46.1 per 1000 person-years in men and 36.8 per 1000 person-years in women, while isolated impaired fasting glucose had the highest incidence rate among all pre-diabetes phenotypes. In both sexes, age, family history of diabetes, fasting plasma glucose and 2-hour post-challenge plasma glucose were related to incident pre-diabetes. Among women, waist-to-height ratio [HR: 1.02 (1.00-1.03)] and being divorced/widowed compared with married [HR: 0.67 (0.52-0.87)] were significant predictors of pre-diabetes; whereas among men, community-based intervention [HR: 0.79 (0.68-0.90)], higher level of education and being single [HR: 0.77 (0.6-0.97)] were protective against progression to pre-diabetes. Moreover, hip circumference among women [HR: 0.95 (0.93-0.98)] and current smoking among men [HR: 1.69 (1.15-2.48)] were related to incident combined impaired fasting glucose and impaired glucose tolerance. CONCLUSION: More than 4% of the Iranian population develop pre-diabetes each year, emphasizing the important role of socio-economic factors (marital status, education and smoking habits) and community-based intervention in progression to impaired glucose regulations. Thus, emergent intervention is necessary to halt the tsunami of pre-diabetes among the Iranian population.

The effect of a single dose of vitamin D on glycemic status and C-reactive protein levels in type 2 diabetic patients with ischemic heart disease: a randomized clinical trial.

AIMS: To assess whether a single parental dose of 25-hydroxy vitamin D [25(OH)Vit D] could improve glucose control and inflammation in type 2 diabetic patients (T2D) with ischemic heart disease (IHD). METHODS: A randomized, placebo-controlled, double-blind trial was performed on 95 patients (47-placebo and 48-vitamin D groups). Participants were randomized using a randomization table to a single dose of either vitamin D (300,000 IU, IM) or a matching placebo. Fasting blood sugar (FBS), glycosylated hemoglobin (HbA1c), 25(OH)Vit D and high-sensitivity C-reactive protein (hs-CRP) were measured at baseline and at 8 weeks. RESULTS: No significant differences in baseline values were noted between groups, except in HbA1c, which was lower in the placebo group. In the supplemented group, the level of serum 25(OH)Vit D increased (29.6 ± 20.8 vs. 44.5 ± 19.2 ng/mL) and those of FBS and HbA1c decreased significantly [186.5 ± 64.1 vs. 165.1 ± 58.5 mg/dL and 8.2 ± 2.0 % (66.3 ± 21.8 mmol/mol) vs. 7.7 ± 1.8 % (61.7 ± 20.0 mmol/mol), respectively] (all p < 0.05), and no changes, however, were observed in the placebo group. We also compared change of marginal means of outcome variables (HbA1c, FBS, 25(OH)Vit D and hs-CRP) from baseline between the vitamin D versus placebo group, using ANCOVA, adjusted for the baseline of each variable itself, season at study entry, age and body mass index. During trial, only HbA1c level decreased significantly [0.48 % (standard error: 0.17), p = 0.04]. No any adverse effect was seen. CONCLUSIONS: A single parenteral dose of vitamin D in T2D patients with IHD improved glycemic control, but not inflammatory status. CLINICAL TRIAL REGISTRY: Australian New Zealand Clinical Trial Registry. CLINICAL TRIAL NUMBER: ACTRN12614000529640.

Wrist circumference as a novel negative risk factor for cardiovascular disease among adult men: a median follow-up of 9 years.

PURPOSE: Wrist circumference is an easy to measure anthropometric index of body frame and bone size. The aim of this study was to examine the association of wrist circumference with incidence of cardiovascular disease (CVD) among adult men. METHODS: For this study 2531 male participants aged ≥30 years, without any history of CVD were selected and followed from 1999 to 2011. Cox proportional hazard models and logistic regression were used to examine the relation of wrist circumference with incident CVD. RESULTS: A total of 339 cases of CVD were reported throughout a median follow-up of 9.4 years. In the multi-variable Cox model, 1 unit increase of wrist circumference was inversely associated with incident CVD with a HR (95 % CI) of 0.84 (0.72-0.98, P value = 0.02). The receiver operating characteristics curve in a logistic regression model for wrist circumference in prediction of CVD showed a cutoff of 17.75 cm, beyond which was associated with a lower risk for CVD. CONCLUSION: In a population with a high prevalence of CVD risk factors, it was shown that a higher wrist circumference was associated with lower risk for incident CVD. Further studies are needed to explore the underlying mechanisms of this inverse relation.

Presence of hypertension modifies the impact of insulin resistance on incident cardiovascular disease in a Middle Eastern population: the Tehran Lipid and Glucose Study.

AIMS: To examine the independent impacts of the homeostasis model assessment of insulin resistance (HOMA-IR) and the updated model (HOMA2-IR) on incident cardiovascular /coronary heart disease in a Middle Eastern population with a high prevalence of cardiovascular disease risk factors. METHODS: We examined 3777 Iranian people, aged ≥ 30 years, without history of cardiovascular disease and without use of antidiabetic medication at baseline. Both HOMA-IR and HOMA2-IR were log-transformed and categorized into quartiles. The multivariable Cox proportional hazard regression model, adjusted for traditional cardiovascular disease risk factors, was applied to examine the association between HOMA-IR/HOMA2-IR with incident cardiovascular/coronary heart disease, considering the lowest quartile as reference. RESULTS: During a median follow-up of > 10 years, 197 cardiovascular disease and 181 coronary heart disease events occurred. Among the covariates, we found a significant interaction between hypertension and HOMA-IR/HOMA2-IR for incident coronary heart/cardiovascular disease (all P ≤ 0.01). Among the population without hypertension, the risk of cardiovascular disease significantly increased in the second [hazard ratio 1.96 (95% CI 1.04-3.68)], third [hazard ratio 1.93 (95% CI 1.00-3.75)] and fourth [hazard ratio 2.34 (95% CI 1.15-4.75)] quartiles of HOMA-IR, and the risk of coronary heart disease increased significantly in the fourth quartile of HOMA-IR [hazard ratio 2.30 (95% CI 1.12-4.73)], but no significant association was detected between HOMA-IR and cardiovascular/coronary heart disease in the population with hypertension. Among the populations both with and without hypertension, no risk was found to be associated with HOMA2-IR quartiles however, a 1-unit increase in HOMA2-IR was associated with a significant risk of cardiovascular disease among the non-hypertensive group [hazard ratio 1.60 (95% CI 1.03-2.48); P = 0.03]. CONCLUSIONS: The presence of hypertension modified the impact of HOMA-IR/HOMA2-IR on incident cardiovascular/coronary heart disease. The presence of insulin resistance highlighted a significant and independent risk for cardiovascular disease/coronary heart disease only in the population without hypertension.

Silent coronary artery disease and incidence of cardiovascular and mortality events at different levels of glucose regulation; results of greater than a decade follow-up.

BACKGROUND: To determine the impact of silent coronary artery disease (CAD), in different levels of glucose regulation at baseline, i.e., those with normal fasting glucose/normal glucose tolerance (NFG/NGT), pre-diabetic and newly diagnosed diabetes mellitus (NDM), on cardiovascular disease (CVD) and total mortality in Iranian populations. METHODS: The study population included 1809 individuals, aged ≥50years, free of CVD at baseline with a median follow-up of 12.1years. To explore the risk of CVD and mortality associated with the presence of silent CAD (as defined by Minnesota coding criteria for baseline electrocardiogram (ECG) in the absence of a history of CVD) in each of the glucose regulation categories, multivariate adjusted hazard ratios (HRs) were calculated for the presence of silent CAD, compared to the corresponding non-silent CAD counterpart, as reference. RESULTS: During follow-up 382 CVD (321 coronary heart disease) and 208 deaths (91 CVD mortality) occurred. Among the female population, the presence of silent CAD, independent of traditional risk factors, significantly increased the risk of CVD for population with NFG/NGT [2.40 (1.33-4.35)] and pre-diabetes [HR: 2.04 (1.14-3.63)]; however, in the male population the risk was significant for CVD [3.04 (1.53-6.05)] and mortality events [2.60 (1.22-5.56)] in the NDM population and marginally significant for mortality events in NFG/NGT. CONCLUSION: Different strategies should be considered for silent CAD in males and females with different levels of glucose regulation. It might be justified that screening ECG for prevention of CVD events should be considered mainly among non-diabetic women and men with NDM.

Relationship of hyperinsulinaemia, insulin resistance and ß-cell dysfunction with incident diabetes and pre-diabetes: the Tehran Lipid and Glucose Study.

AIMS: To examine the association of fasting insulin, insulin resistance and reduced ß-cell function with incident Type 2 diabetes and pre-diabetes (isolated impaired fasting glucose/isolated impaired glucose tolerance and combined impaired fasting glucose/impaired glucose tolerance). METHODS: An Iranian population comprising 1532 men and 2221 women, aged ≥ 20 years, with normal fasting glucose and normal glucose tolerance at baseline, were enrolled in the study. Multivariable Cox proportional hazard models were used to calculate the hazard ratios and 95% CIs of fasting insulin, updated homeostasis model assessments of insulin resistance and ß-cell function for incident Type 2 diabetes, isolated impaired fasting glucose, isolated impaired glucose tolerance and combined impaired fasting glucose/impaired glucose tolerance. RESULTS: During a median follow-up of 9.2 years, the annual incidence rates (95% CI) of diabetes were 3.73 (2.74-4.94) and 4.06 (3.21-5.06) per 1000 person-years in men and women, respectively. In both men and women, fasting insulin and homeostasis model assessment of insulin resistance (≥ 75th percentile) were significantly associated with incident diabetes and combined impaired fasting glucose/impaired glucose tolerance; however, reduced ß-cell function as measured by homeostasis model assessment of ß-cell function (< 25th percentile) was associated with incident isolated impaired fasting glucose solely in men [hazard ratio 1.35 (95% CI 1.02-1.78)] in multivariable analysis including waist-hip ratio). Hyperinsulinaemia, insulin resistance and ß-cell dysfunction were not related to the incidence of isolated impaired glucose tolerance in either gender. CONCLUSIONS: Fasting hyperinsulinaemia and insulin resistance were strong risk factors for progression to diabetes and combined impaired fasting glucose/impaired glucose tolerance in a population with normal fasting glucose/normal glucose tolerance. In addition, impaired ß-cell function at baseline was related to the development of isolated impaired fasting glucose only in men and, in both men and women, neither insulin resistance nor ß-cell dysfunction were associated with incident isolated impaired glucose tolerance.

Changes in body mass index, waist and hip circumferences, waist to hip ratio and risk of all-cause mortality in men.

BACKGROUND: There is a paucity of data about the impact of changes in anthropometric measurements on the risk of mortality events, especially in men. METHODS: The study sample consists of 1805 Iranian men, aged ⩾ 30 years, free from cardiovascular disease at baseline; they had undergone health examinations in both phases I (1999-2001) and II (2001-2003) and were followed up until March 2010. Participants were categorized by changes in anthropometric measurements into four groups: Group 1, change percentage<-5%; Group 2, -5% ⩽ change percentages<+5%; Group 3, 5% ⩽ change percentage<10%; and Group 4, change percentage ⩾ 10%. Cox proportional hazard regression was performed to assess the hazard ratios (HRs) of the anthropometric changes for all-cause mortality, given group 2 as the reference. RESULTS: During 6.6 years of follow-up, 88 cases of mortality events occurred. The confounder-adjusted multivariate HRs for the first, third and fourth groups of hip circumference (HC) changes were 3.13(1.28-7.64), 0.75(0.43-1.31) and 0.82(0.23-2.99); the corresponding values for waist to hip ratio (WHR) change were 1.80(0.75-4.33), 1.21(0.70-2.1) and 2.32(1.25-4.3). After further adjustment for mediator covariates, results did not change. The equivalent values for body mass index and waist circumference did not reach statistical significance. CONCLUSIONS: In Middle Eastern Caucasian men, increase in WHR was associated with incident mortality, which was more prominent in those with ⩾ 10% increase in the ratio. Moreover, decrease in HC was highly associated with excess risk of mortality.

Sex-specific relations between fasting insulin, insulin resistance and incident hypertension: 8.9 years follow-up in a Middle-Eastern population.

The purpose of this study was to investigate whether fasting serum insulin levels, homeostasis model assessment of insulin resistance (HOMA-IR) and insulin-to-glucose ratio (IGR) were associated with incident hypertension. In a prospective study, 4093 Iranian participants (1725 men and 2368 women) without hypertension and known diabetes at baseline (1999-2001) were followed for a median of 8.9 years. Regular follow-up examinations were performed at 3-year intervals. Multivariate Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension adjusting for sex, and in sex-stratified models. During the study, 896 incident cases of hypertension (432 men and 464 women) were identified (total incident rate: 27.5 per 1000 person-years). In the multivariable models, serum insulin level, HOMA-IR and IGR were positively associated with hypertension incidence, adjusting for sex. In the sex-stratified analyses, after adjusting for potential confounders, women in the highest quartile of insulin, HOMA-IR and IG had a significantly higher incidence of hypertension, compared with those in the lowest quartile (HR: 1.7 (95% CI 1.26-2.30); HR: 1.80 (95% CI 1.31-2.40) and HR: 1.67 (95% CI 1.26-2.22), respectively); among men, these relations were also significant, until including waist circumference and body mass index in the models (HR: 1.17 (95% CI 0.85-1.62), HR: 1.25 (95% CI 0.91-1.73) and HR: 1.06 (95% CI 0.77-1.45), respectively). Higher fasting serum insulin levels, HOMA-IR and IGR were associated with incident hypertension among women, whereas these associations were not significant after adjusting for obesity measures in men.

Added value of different metabolic syndrome definitions for predicting cardiovascular disease and mortality events among elderly population: Tehran Lipid and Glucose Study.

BACKGROUND/OBJECTIVES: To examine the association between the different definitions of metabolic syndrome (MetS) and the prediction of incident cardiovascular disease (CVD) and mortality events and to determine whether the concept of MetS adds to traditional risk factors among elderly Iranians. SUBJECTS/METHODS: The association between MetS and outcomes was examined in 922 adults aged ⩾65 years, free of CVD at baseline, using multivariate Cox proportional hazards models. To examine whether MetS could enhance prediction of outcomes beyond that achieved by risk factors; the net reclassification improvement index was used. RESULTS: During a median follow-up of 9.9 years, 207 CVD events and 193 deaths (82 CVD deaths) occurred. World health organization (WHO) and the joint interim statement (JIS) definitions were shown to be the strongest predictors of CVD events. The WHO definition predicted CVD and all-cause mortality events (hazard ratio (HR)=1.55 (95% confidence interval (CI)=1.15-2.09) and 2.08 (95% CI=1.23-3.51), respectively) and the JIS definition showed a risk for CVD mortality (HR=1.65 (95% CI=1.03-2.65)). Different definitions of MetS did not add to traditional risk factors in the prediction of different outcomes. CONCLUSIONS: The WHO definition was the strongest predictor of CVD and mortality outcomes; however, none of the MetS definitions provided added value to traditional risk factors.

Non-linear association between 25-hydroxyvitamin D and the incidence of type 2 diabetes: a community-based nested case-control study.

AIMS: To examine the nature of the association between 25-hydroxyvitamin D [25(OH)D] and newly diagnosed type 2 diabetes. METHODS: Serum 25(OH)D concentrations were measured for 761 participants (aged 20-83 years) in the Tehran Lipid and Glucose Study, selected for a 1-to-3 nested case-control study. Cases were 191 cases of Type 2 diabetes diagnosed during a median follow-up of 3.6 years. A total of 570 participants were matched with these cases with regard to age, sex, BMI, and month of entering the study. Diabetes was defined according to the American Diabetes Association criteria, 2003. Serum 25(OH)D was measured using the enzyme immunoassay method. Odds ratios for Type 2 diabetes were obtained from conditional logistic regression models for tertiles of serum 25(OH)D concentrations [tertile-1: 2.82-11.02 (reference), tertile-2: 11.03-21.80, and tertile-3: ≥ 21.82 ng/ml]. The multivariate model was adjusted for age, sex, family history of diabetes, systolic blood pressure, triglyceride-to- HDL cholesterol ratio, waist-to-height ratio, lifestyle modification intervention, leisure time physical activity, and fasting plasma glucose at baseline. Non-linearity in the associations between baseline 25(OH)D and Type 2 diabetes, was examined by using restricted cubic splines. RESULTS: Unadjusted odds ratios (95% confidence intervals) of diabetes were 0.73 (0.74-1.13), 0.54 (0.34-0.85) for the second and third tertiles, respectively. Multivariate adjusted odds ratios were 0.47 (0.25-0.90) and 0.43 (0.23-0.82), respectively. Below the cutoff of ~ 10 ng/ml the risk of newly diagnosed Type 2 diabetes increased dramatically. DISCUSSION: It was found that 25(OH)D concentrations contributed to the Type 2 diabetes incidence rate in a non-linear fashion, with the risk beginning to increase sharply for values < 10 ng/ml.

High normal blood pressure is an independent risk factor for cardiovascular disease among middle-aged but not in elderly populations: 9-year results of a population-based study.

Data are conflicting and sparse regarding the impact of high normal blood pressure (BP) (systolic BP (SBP) of 130-139 mm Hg or diastolic BP (DBP) of 85-89 mm Hg) on incident cardiovascular disease (CVD) among middle-aged vs elderly population. We examined the risk of BP categories among 6273 participants ≥ 30 years, free of CVD at baseline, during more than 9.3 years follow-up. Cox regression analysis was used to estimate the hazard ratio (HR) of CVD for normal BP group (SBP between 120-129 mmHg or DBP between 80-85 mmHg), high normal BP group and hypertension group (SBP ≥ 140 mm Hg or DBP ≥ 90 mmHg or taking antihypertensive drugs), considering those with optimal BP (SBP<120 mmHg and DBP<80 mmHg) as reference. During follow-up, 512 CVD events occurred. There was significant interaction between age and BP categories (P=0.028) in prediction of CVD. In multivariate analysis, HRs (95% CIs) of CVD were 1.62 (1.11-2.37) and 2.20 (1.57-3.09) for middle aged with high normal and hypertensive BP groups, respectively. Among elderly (≥ 60 years), HR was 2.09 (1.36-3.21) only for hypertensive ones. High normal BP is a risk factor for incident of CVD only among middle-aged population. Furthermore, the effect of hypertension on incident CVD was stronger among younger population.

Cardiovascular risk and all-cause mortality attributable to diabetes: Tehran lipid and glucose study.

AIM: To quantify the burden of cardiovascular diseases (CVD), and all-cause mortality attributable to diabetes. SUBJECTS AND METHODS: Data on an 8.6-yr follow-up of 6331 participants (2741 men), free of CVD at baseline, were analyzed to determine the burden of CVD and all-cause mortality attributable to self-reported and screen-detected diabetes mellitus (SRDM and SDDM, respectively). Risks of events of interest were separately assessed for women and men using Cox-proportional-hazard model. RESULTS: The mean age at baseline was 47 yr with 997 (15.7%) of participants having diabetes (men 14.8%, women 16.5%). SRDM and SDDM prevailed in 9.7% (men 9.2, women 10.2%) and 6.0% of participants (men 5.7, women 6.3%), respectively. During follow up (52,404 person-yr), we observed 447 incident cases of CVD [387 had coronary heart disease (CHD)] and 209 deaths. Among men, participants with SDDM had increased relative hazard for all-cause mortality translated to a population attributable risk fraction (PAF) of 10.1%. Among women, SDDM was associated with CVD and CHD but not with all-cause mortality; so that 9.3% and 8.8% of CVD and CHD events were respectively attributable to the SDDM. If SRDM had been eliminated from the population, the incidences of CVD, CHD, and death would have decreased by 10.5, 9.5, and 17.3% in men; and 22.0, 24.2, and 17.8% in women, respectively. CONCLUSION: SDDM and SRDM have high PAF for all-cause mortality and CVD. Besides diabetes treatment and prevention, screening to detect undiagnosed diabetes should warrant high priority among the public health strategies to lower the incidence of CVD and mortality.

A new approach to compare the predictive power of metabolic syndrome defined by a joint interim statement versus its components for incident cardiovascular disease in Middle East Caucasian residents in Tehran.

BACKGROUND: Metabolic syndrome (MS) has an increased risk for developing cardiovascular disease (CVD); however, whether the concept of MS, applying the new joint interim statement definition, has a greater impact on incident CVD than its individual components is debated. METHODS: The authors related MS and its components to CVD incidence in 1856 men and 2392 women, Iranian adults aged ≥40 years, free of CVD at baseline, using Cox proportional hazards models. To examine whether MS would improve prediction of CVD beyond that achieved by its components; model fitness, discrimination and integrated discrimination improvement (IDI) statistics were used. RESULTS: During a median follow-up of 8.6 years, there were 244 CVD events in men and 189 in women. MS resulted in HRs (95% CIs) of 1.97 (1.50 to 2.57) in men and 2.25 (1.57 to 3.21) in women after adjusting for CVD risk factors; in another model including all the five MS components, high blood pressure in both genders [men: 1.99 (1.48 to 2.67), women: 1.62 (1.14 to 2.30)), high waist circumference (≥94.5 cm) in men (1.47 (1.12 to 1.93)) and high fasting plasma glucose (FPG) in women (1.88 (1.39 to 2.55)) remained as independent predictors of CVD after adjusting for CVD risk factors. Adding the MS variable to this model did not yield any improvement in model fitness, C-statistic or significant IDI value. CONCLUSION: In the Middle East population, MS did not provide CVD predictive risk information beyond its individual components; clinical focus should remain on hypertension in both sexes, high FPG in women and central adiposity in men rather than MS.

Family history of diabetes modifies the effect of blood pressure for incident diabetes in Middle Eastern women: Tehran Lipid and Glucose Study.

Elevated blood pressure (BP) may lead to incident diabetes. However, data about the effect of different BP components on incident diabetes in Middle Eastern women is lacking. We evaluated systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP) and mean arterial pressure (MAP) as independent predictors of diabetes in Iranian women. We performed a population-based prospective study among 3028 non-diabetic women, aged ≥20 years. Odds ratios (ORs) of diabetes were calculated for every 1 s.d. increase in SBP, DBP, PP and MAP. During ≈6 years of follow-up, 220 women developed diabetes. There were significant interactions between family history of diabetes and SBP, PP and MAP (P≤0.01) in predicting incident diabetes. In women without a family history of diabetes, all BP components were significantly associated with diabetes in the age-adjusted model; the risk factor-adjusted ORs were significant (P<0.05) for SBP, PP and MAP (1.30, 1.34 and 1.27, respectively) with similar predictive ability (area under the receiver operating characteristic curve ≈83%). In women with family history of diabetes, in the age-adjusted model, SBP, DBP and MAP were associated with diabetes; in multivariable model, they were not independent predictors of diabetes. In conclusion, in women without family history of diabetes, SBP, PP and MAP, were independent predictors of diabetes with almost similar predictive ability; hence, in the evaluation of the risk of BP components for prediction of diabetes, the presence of family history of diabetes should be considered.