Endogenous estrogen exposure and hypertension risk; a population-based cohort study with about two decades of follow-up.

CONTENT: The impact of endogenous estrogen exposure (EEE) on hypertension (HTN) incidence has not been investigated yet. OBJECTIVE: This study aimed to evaluate HTN incidence in women with different endogenous estrogen durations. METHODS: Information was gathered from the Tehran Lipid and Glucose Study (TLGS) to conduct current research. At the initiation of the study, 4463 post-menarche normotensive women, including 3599 premenopausal and 864 menopausal women, were included. EEE was calculated for each woman, and they were followed up for the HTN event. According to the EEE, the hazard ratios and 95% confidence intervals (CI) for the HTN event were presented using Cox proportional hazards regression models (unadjusted and adjusted). RESULTS: The median (interquartile range) of follow-up (between menarche and the date of HTN incidence or last follow-up) was 33.2(25.1, 42.3) years. The event of menopause occurred in 31.8% of participants. The unadjusted model's findings illustrated that the EEE z-score was inversely associated with HTN incidence in post-menarcheal women [unadjusted hazard ratio (HR) 0.47, 95% CI 0.44, 0.50], meaning that the risk of HTN decreased by 53% for every 1-SD rise in the EEE z-score. After adjusting for potential confounders, the results showed no statistically significant changes (adjusted HR 0.46, 95% CI 0.43-0.49). In participants with prehypertension at baseline, the hazard of HTN decreased by 56% per 1-SD rise in the EEE z-score. CONCLUSION: This longitudinal study demonstrated the protective effect of a longer EEE duration on HTN risk, even among those with prehypertension status.

The association of body mass index variability with cardiovascular disease and mortality: a mediation analysis of pooled cohorts.

Aim: We aimed to investigate the effect of BMI variability on CVD and mortality and to explore the mediation effects of the main cardiovascular risk factors contributing to this association. Method: Participants aged 40-65 years were pooled from three cohort studies(ARIC [Atherosclerosis Risk in Communities], MESA [Multi-ethnic Study of Atherosclerosis], and TLGS [Tehran Lipid and Glucose Study]. We employed root mean squared error of the fractional mixed model to calculate BMI variability in the measurement period. In the event assessment period, the hazard ratios for CVD and mortality were estimated using Cox proportional hazard regression models. In the next step, the mediation and interaction effects of fasting plasma glucose, total cholesterol, and systolic blood pressure were determined. Results: A total of 19073 participants were included in this pooled analysis. During a median of 20.7 years of follow-up, 3900 (20.44%) CVD and 6480 (33.97%) all-cause mortality events were recorded. After adjusting for potential confounders, BMI variability was linked to the 1.3 (1.2-1.4) and 1.7 (1.6-1.8) increased risk of CVD and mortality, respectively. Fasting plasma glucose mediated approximately 24% and 8% of the effect of BMI variability on CVD and mortality, respectively. However, systolic blood pressure and total cholesterol did not have mediation effects in this association. Conclusion: High BMI variability is independently associated with the development of CVD and mortality. This association is partly mediated through fasting plasma glucose. Modern cardiometabolic therapies that lower fasting glucose may reduce the risk of future CVD and mortality in individuals with high BMI variability.

Association Between Insulin Resistance Indices and Liver Function Parameters Among Women With Polycystic Ovary Syndrome.

OBJECTIVE: This study aimed to investigate whether polycystic ovary syndrome (PCOS) status changes the association between insulin resistance (IR) indices and liver function parameters among women. METHODS: This is a cross-sectional, population-based study. We selected 1101 subjects aged ≥20 years from participants of Tehran Lipid and Glucose Study (TLGS). All of them had known the status of PCOS, and all variables were related to the IR indices and liver function parameters. The main outcome measures were TG/HDL-C and triglyceride-glucose (TyG) and liver function parameters (hepatic steatosis index [HSI], alanine transaminase [ALT] and aspartate transaminase [AST]). RESULT: In the present study, there was no significant difference between the PCOS and the non-PCOS regarding the presence of liver function abnormalities. A model adjusted by age and BMI showed that the upper tertile of TyG index was positively associated with high AST (OR = 3.04 [95% CI: 1.20-7.68], p < 0.05), high ALT (4.76 [3.07-7.36], p < 0.05) and high HSI (8.44 [1.82-39.17], p < 0.05). Although the history of diabetes had a positive impact on elevated AST (1.66 [1.15, 2.40], p < 0.05), the third tertile of TG/HDL-C was associated with increased odds of elevated ALT (3.35 [2.21-5.06]) and HSI (6.55 [1.17-36.46]), whereas the second tertile of TG/HDL-C (OR = 2.65, CI 95%: 1.74-4.03) was also positively associated with elevated ALT. PCOS had no significant association with elevated liver function tests. CONCLUSION: The highest tertile of TyG index and the TG/HDL-C ratio as a surrogate of IR might play a role in detecting abnormalities of liver function parameters among women. However, PCOS status cannot change the association between IR and liver dysfunction.

Sirtfood intake in relation to the 10-year risk of major adverse cardiovascular events: a population-based cohort study.

BACKGROUND: Sirtuins have an important role in the regulation of metabolic and biological processess. Thus, we hypothesized that foods that could activate sirtuins, known as "sirtfood", may improve health status. So, this study was aimed at investigating the association between the amount of sirtfood intake and the risk of major adverse cardiovascular events (MACE). METHODS: In this cohort study, 2918 adults who had no history of MACE at the start of the study (2006-2008) participated and were followed up on until 2018. The amount of sirtfoods intake (servings per week) was computed using a validated food frequency questionnaire. Each patient's medical records were evaluated to detect MACE. The Cox proportional hazards model was applied to assess the association between the amount of sirtfood intake and the risk of MACE. RESULTS: The median duration of the study was 10.6 years. The hazard ratio (HR) for the risk of MACE was 0.70 for the second (95% CI: 0.50, 0.98) and 0.60 (95% CI: 0.42, 0.86) for the third tertile of sirtfoods intake compared with the first tertile. This association was nonlinear, and sirtfoods consumption of more than five servings per week did not result in a lower risk of MACE. In addition, there was a significant interaction between age (P-interaction < 0.001) and sirtfoods intake in relation to MACE occurrence. When assessing sirtfood components, compared with the lowest intake, the highest amount of soy (HR: 0.74, 95% CI: 0.56, 0.99) and parsley (HR: 0.62, 95% CI: 0.47, 0.83) intake was related to a lower risk of MACE. CONCLUSION: Our results indicated an inverse association between a higher amount of sirtfood intake and a lower risk of MACE incidents. This association was nonlinear, and having more than five servings of sirtfood per week did not reduce the risk of MACE any further.

Socio-behavioral determinants of health-related quality of life among patients with type 2 diabetes: comparison between 2015 and 2018.

INTRODUCTION: Type 2 diabetes (T2D) is a common chronic disease that significantly affects an individual's overall health and well-being. The aim of this study is to investigate the factors that influence the health-related quality of life (HRQoL) of patients with T2D. METHODS: This study conducted using data from 6th phase (2015-2017) and 7th phase (2018-2022) of the Tehran Lipid and Glucose Study (TLGS). Data were collected through a combination of interviews, physical examinations, and laboratory tests. Quality of life questionnaire (SF-12) that consists of 12 questions was used to assess physical and mental health functioning. The generalized estimating equation model was used to assess the association between socio-behavioral factors and changes in HRQoL. RESULTS: The study included 498 patients with T2D. The changes in HRQoL in patients with T2D followed a sex-specific pattern. Analysis of the physical component score (PCS) and the mental component score (MCS) showed a non-significant change in the total score during the three-year longitudinal study. However, the role physical (RP) of the PCS and the social functioning (SF) of the MCS showed a statistically significant change during this period. In addition, sex, body mass index (BMI), and having cardiovascular disease (CVD) and chronic kidney disease (CKD) showed a significant association with RP changes, and only job status showed a significant association with SF changes. CONCLUSIONS: By recognizing the sex-specific patterns in HRQoL changes and understanding the multifaceted nature of factors such as BMI, CVD and CKD, healthcare professionals can develop targeted interventions that go beyond traditional diabetes management.

The effect of obesity phenotype changes on cardiovascular outcomes in adults older than 40 years in the prospective cohort of the Tehran lipids and glucose study (TLGS): joint model of longitudinal and time-to-event data.

BACKGROUND: Obesity is a worldwide health concern with serious clinical effects, including myocardial infarction (MI), stroke, cardiovascular diseases (CVDs), and all-cause mortality. The present study aimed to assess the association of obesity phenotypes and different CVDs and mortality in males and females by simultaneously considering the longitudinal and survival time data. METHODS: In the Tehran Lipid and Glucose Study (TLGS), participants older than three years were selected by a multi-stage random cluster sampling method and followed for about 19 years. In the current study, individuals aged over 40 years without a medical history of CVD, stroke, MI, and coronary heart disease were included. Exclusions comprised those undergoing treatment for CVD and those with more than 30% missing information or incomplete data. Joint modeling of longitudinal binary outcome and survival time data was applied to assess the dependency and the association between the changes in obesity phenotypes and time to occurrence of CVD, MI, stroke, and CVD mortality. To account for any potential sex-related confounding effect on the association between the obesity phenotypes and CVD outcomes, sex-specific analysis was carried out. The analysis was performed using packages (JMbayes2) of R software (version 4.2.1). RESULTS: Overall, 6350 adults above 40 years were included. In the joint modeling of CVD outcome among males, literates and participants with a family history of diabetes were at lower risk of CVD compared to illiterates and those with no family history of diabetes in the Bayesian Cox model. Current smokers were at higher risk of CVD compared to non-smokers. In a logistic mixed effects model, odds of obesity phenotype was higher among participants with low physical activity, family history of diabetes and older age compared to males with high physical activity, no family history of diabetes and younger age. In females, based on the results of the Bayesian Cox model, participants with family history of diabetes, family history of CVD, abnormal obesity phenotype and past smokers had a higher risk of CVD compared to those with no history of diabetes, CVD and nonsmokers. In the obesity varying model, odds of obesity phenotype was higher among females with history of diabetes and older age compared to those with no history of diabetes and who were younger. There was no significant variable associated with MI among males in the Bayesian Cox model. Odds of obesity phenotype was higher in males with low physical activity compared to those with high physical activity in the obesity varying model, whereas current smokers were at lower odds of obesity phenotype than nonsmokers. In females, risk of MI was higher among those with family history of diabetes compared to those with no history of diabetes in the Bayesian Cox model. In the logistic mixed effects model, a direct and significant association was found between age and obesity phenotype. In males, participants with history of diabetes, abnormal obesity phenotype and older age were at higher risk of stroke in the Bayesian Cox model compared to males with no history of diabetes, normal obesity phenotype and younger persons. In the obesity varying model, odds of obesity phenotype was higher in males with low physical activity, family history of diabetes and older age compared to those with high physical activity, no family history of diabetes and who were younger. Smokers had a lower odds of obesity phenotype than nonsmokers. In females, past smokers and those with family history of diabetes were at higher risk of stroke compared to nonsmokers and females with no history of diabetes in the Bayesian Cox model. In the obesity varying model, females with family history of diabetes and older ages had a higher odds of obesity phenotype compared to those with no family history of diabetes and who were younger. Among males, risk of CVD mortality was lower in past smokers compared to nonsmokers in the survival model. A direct and significant association was found between age and CVD mortality. Odds of obesity phenotype was higher in males with a history of diabetes than in those with no family history of diabetes in the logistic mixed effects model. CONCLUSIONS: It seems that modifications to metabolic disorders may have an impact on the heightened incidence of CVDs. Based on this, males with obesity and any type of metabolic disorder had a higher risk of CVD, stroke and CVD mortality (excluding MI) compared to those with a normal body mass index (BMI) and no metabolic disorders. Females with obesity and any type of metabolic disorder were at higher risk of CVD(, MI and stroke compared to those with a normal BMI and no metabolic disorders suggesting that obesity and metabolic disorders are related. Due to its synergistic effect on high blood pressure, metabolic disorders raise the risk of CVD.

Cigarette smoking and cardiovascular disease incidence and all-cause mortality: the modifying role of diet quality.

BACKGROUND: This study examines the potential long-term joint association between smoking and diet quality as modifiable risk factors concerning cardiovascular diseases (CVDs) incidence and all-cause mortality among current and former smokers. METHODS: The study followed 955 smokers from the third and fourth examinations of the Tehran Lipid and Glucose Study to March 2018. Dietary data was collected using a food frequency questionnaire. Three diet quality indices (DQIs) were computed at baseline: DQI-international (DQI-I), DQI-revised (DQI-R), and Mediterranean-DQI (Med-DQI). Cox proportional hazards regression models were used to determine the HR (95% CI) of the joint association between smoking and diet quality among heavy and light smokers, based on the number of cigarettes per day and pack-years, as well as between current and former smokers based on smoking habits. RESULTS: Over a follow-up period of almost eight years, 94 cases of CVDs (9.80%) and 40 cases of mortality (4.20%) were documented. The lower diet quality based on the Med-DQI was associated with a higher risk of mortality among current smokers (HR:3.45; 95%CI:1.12, 10.57). Light smokers with good diet quality, compared to heavy smokers with poor diet quality, had a lower risk of CVDs incident (HR:0.35; 95%CI: 0.15, 0.83) and all-cause mortality (HR:0.20; 95%CI:0.05, 0.77). Current smokers with good DQI had a lower risk of mortality compared to current smokers with poor DQI (HR:0.26; 95%CI:0.08, 0.80). However, this lower risk was more significant in former smokers with good DQI (HR:0.10; 95%CI:0.02, 0.45). CONCLUSIONS: Light and former smokers had a lower risk of developing CVDs and experiencing mortality. However, when coupled with a high-quality diet, this protective effect is even more pronounced.

Usual intake of dairy products and the chance of pre-diabetes regression to normal glycemia or progression to type 2 diabetes: a 9-year follow-up.

BACKGROUND: We assessed the possible effect of usual dairy consumption on pre-diabetes (Pre-DM) remission or progression to type 2 diabetes (T2D). METHODS: Pre-DM adults (n = 334, mean age of 49.4 years, and 51.5% men) were assessed for dairy intakes (2006-2008) and followed up to 9 years for incidence of T2D or normal glycemia (NG). All biochemical measurements were done at baseline and all subsequent examinations with 3-y follow-up intervals. Multinomial regression models with adjustment of confounding variables were used to estimate odds ratios (OR) and 95% confidence intervals (CIs) of incident T2D and NG for each serving/d dairy consumption. RESULTS: The odds of NG was significantly elevated by 69% (OR = 1.69, 95% CI = 1.00-2.86, P = 0.05) per 200 g/d increased high-fat dairy intake, while the amount of total dairy or low-fat dairy was not related to the outcomes. Higher intakes of yogurt were more likely to be associated with an increased odds of NG (OR = 1.82, 95% CI = 1.20-2.74, P = 0.01). Usual intakes of milk, cheese, or cream-butter were not associated to Pre-DM remission or progression to T2D. CONCLUSION: Regular dairy consumption may increase the chance of Pre-DM regression to NG.

Association Between HDL2-C and HDL3-C with Cardiovascular Disease: A Nested Case-Control Study in an Iranian Population.

Background: The contribution of high-density lipoprotein cholesterol (HDL-C) subclasses to incident cardiovascular disease (CVD) and coronary heart disease (CHD) remains a subject of debate. Objectives: The objective of this study was to investigate these associations in a population with a high prevalence of dyslipidemia and CVD. Methods: In a nested case-control study, HDL-C and its subclasses (HDL2-C and HDL3-C) in 370 age and gender-matched case and control subjects were determined. This study employed multivariable-adjusted conditional logistic regression to calculate the odds ratios (ORs) for the associations between HDL-C, HDL2-C, HDL3-C, and HDL2-C/HDL3-C (both as continuous and categorical variables) with incident CVD and CHD. The present study models were adjusted for a comprehensive set of confounders, including body mass index, current smoking, hypertension, type 2 diabetes mellitus, use of lipid-lowering drugs, family history of premature CVD, non-HDL-C, and triglycerides. Results: In multivariate analysis, when considering lipoprotein parameters as continuous variables, a 1-unit increase in HDL-C and HDL3-C was associated with a reduced risk of incident CVD and CHD. For CVD, the ORs (95% confidence intervals [CI]) were 0.95 (0.92 - 0.98) and 0.95 (0.93 - 0.98) for HDL-C and HDL3-C, respectively. The corresponding values for CHD were 0.94 (0.91 - 0.97) and 0.94 (0.91 - 0.97). In the categorical approach to lipoprotein parameters, higher quartiles of HDL-C and HDL3-C, compared to the first quartile, were significantly associated with a lower risk of incident CVD and CHD. The ORs (95% CI) for the fourth quartiles were 0.43 (0.25 - 0.74, P for trend = 0.003) and 0.46 (0.27 - 0.78, P for trend = 0.005) for HDL-C and HDL3-C regarding CVD and 0.32 (0.17 - 0.59) and 0.32 (0.18 - 0.59) (all P for trend = 0.001) regarding CHD, respectively. Paradoxically, across quartiles of HDL2-C/HDL3-C, this lipid ratio was associated with a higher risk of CHD (92% higher risk in the fourth quartile). Conclusions: The results showed that HDL3-C, but not HDL2-C, was primarily responsible for the protective effect of HDL-C against CVD, particularly CHD, in Iranian adults.

Metabolic health's central role in chronic kidney disease progression: a 20-year study of obesity-metabolic phenotype transitions.

This study investigates the risk of chronic kidney disease (CKD) across four metabolic phenotypes: Metabolically Healthy-No Obesity (MH-NO), Metabolically Unhealthy-No obesity (MU-NO), Metabolically Healthy-Obesity (MH-O), and Metabolically Unhealthy-Obesity (MU-O). Data from the Tehran Lipid and Glucose Study, collected from 1999 to 2020, were used to categorize participants based on a BMI ≥ 30 kg/m2 and metabolic health status, defined by the presence of three or four of the following components: high blood pressure, elevated triglycerides, low high-density lipoprotein, and high fasting blood sugar. CKD, characterized by a glomerular filtration rate < 60 ml/min/1.72 m2. The hazard ratio (HR) of CKD risk was evaluated using Cox proportional hazard models. The study included 8731 participants, with an average age of 39.93 years, and identified 734 incidents of CKD. After adjusting for covariates, the MU-O group demonstrated the highest risk of CKD progression (HR 1.42-1.87), followed by the MU-NO group (HR 1.33-1.67), and the MH-O group (HR 1.18-1.54). Persistent MU-NO and MU-O posed the highest CKD risk compared to transitional states, highlighting the significance of exposure during early adulthood. These findings emphasize the independent contributions of excess weight and metabolic health, along with its components, to CKD risk. Therefore, preventive strategies should prioritize interventions during early-adulthood.

Causal effect of serum 25 hydroxyvitamin D concentration on cardioembolic stroke: Evidence from two-sample Mendelian randomization.

BACKGROUND AND AIMS: The putative association between serum 25-hydroxyvitamin D concentration [25(OH)D] and the risk of cardioembolic stroke (CES) has been examined in observational studies, which indicate controversial findings. We performed Mendelian randomization (MR) analysis to determine the causal relationship of serum 25(OH)D with the risk of CES. METHODS AND RESULTS: The summary statistics dataset on the genetic variants related to 25(OH)D was used from the published GWAS of European descent participants in the UK Biobank, including 417,580 subjects, yielding 143 independent loci in 112 1-Mb regions. GWAS summary data of CES was obtained from GIGASTROKE Consortium, which included European individuals (10,804 cases, 1,234,808 controls). Our results unveiled a causal relationship between 25(OH)D and CES using IVW [OR = 0.82, 95% CI: 0.67-0.98, p = 0.037]. Horizontal pleiotropy was not seen [MR-Egger intercept = 0.001; p = 0.792], suggesting an absence of horizontal pleiotropy. Cochrane's Q [Q = 78.71, p-value = 0.924], Rucker's Q [Q = 78.64, p-value = 0.913], and I2 = 0.0% (95% CI: 0.0%, 24.6%) statistic suggested no heterogeneity. This result remained consistent using different MR methods and sensitivity analyses, including Maximum likelihood [OR = 0.82, 95%CI: 0.67-0.98, p-value = 0.036], Constrained maximum likelihood [OR = 0.76, 95%CI: 0.64-0.90, p-value = 0.002], Debiased inverse-variance weighted [OR = 0.82, 95%CI: 0.68-0.99, p-value = 0.002], MR-PRESSO [OR = 0.82, 95%CI 0.77-0.87, p-value = 0.022], RAPS [OR = 0.82, 95%CI 0.67-0.98, p-value = 0.038], MR-Lasso [OR = 0.82, 95%CI 0.68-0.99, p-value = 0.037]. CONCLUSION: Our MR analysis provides suggestive evidence that increased 25(OH)D levels may play a protective role in the development of cardioembolic stroke. Determining the role of 25(OH)D in stroke subtypes has important clinical and public health implications.

Tracking correlations and predictors of plasma glucose in young adulthood: A comprehensive analysis from adolescence to young adulthood in TLGS study.

AIMS: We investigated the tracking correlations between fasting plasma glucose (FPG) in adolescence with both FPG and 2-hour post-load glucose (2 h-PG) in adulthood, and identified the predictors of FPG and 2 h-PG in young adulthood using traditional risk factors during adolescence and adulthood. METHODS: We included 2188 participants (1033 male) from the Tehran lipid and glucose study within the age ranges 11-18 and 19-40 years during 1999-2018. The area under the curve (AUC) was computed using the growth curve models, and predictors were identified by the linear regression model. RESULTS: The partial correlation between AUCs of FPG in adolescence and adulthood was 0.37 (P < 0.001). The correlation between AUCs of FPG in adolescence and 2 h-PG in adulthood was 0.17 (P < 0.001). The AUC of FPG was a significant positive predictor for both FPG and 2 h-PG in young adulthood. Other predictors of adult FPG included sex, as well as BMI and the ratio of triglycerides to HDL-cholesterol during both adolescence and adulthood. CONCLUSIONS: Tracking correlation was observed for FPG, suggesting that monitoring and managing risk factors in adolescence may have implications for future glucose metabolism in young adulthood.

Higher ultra-processed food intake is associated with an increased incidence risk of cardiovascular disease: the Tehran lipid and glucose study.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of death worldwide, although limited data are currently available regarding the impact of consuming ultra-processed food (UPF) on its incidence. Given the increased consumption of UPF in Iran, we aimed to investigate the association between UPF intake and CVD risk. METHODS: Individuals without CVD (n = 2050) aged ≥ 30 years old were recruited from the Tehran Lipid and Glucose Study (TLGS). Dietary data were collected using a validated food frequency questionnaire (FFQ) and UPF intakes were assessed based on the Nova food classification. Multivariable Cox proportional hazard models adjusted for potential confounders were used to estimate the hazard ratio (HR) and 95% confidence intervals (95% CI) for the risk of CVD across tertiles of UPF intake. RESULTS: A 10.1% incidence of CVD occurred over a median follow-up of 10.6 years, with a 22% increase in CVD risk per each 50 g/day UPF intake. Participants with the highest intake of UPF had a 68% greater incidence of CVD compared to those with the lowest intake (HR = 1.68, 95% CI=1.14-2.48) after controlling for potential confounders. Regarding sub-groups of UPF, participants in the 3rd tertile compared to the reference had a significantly increased risk of CVD (HR = 1.56, 95% CI=1.04-2.34). Nevertheless, intake of bread, fast food, sweetened beverages, sweets and desserts, high-fat dairy products, and other UPFs were not associated with greater CVD risk. CONCLUSION: Our findings support the hypothesis that the incidence of CVD is enhanced with the higher consumption of UPF in a representative sample of the Iranian population.

The difference between 2-hour post-challenge and fasting plasma glucose associates with the risk of cardiovascular disease in a normoglycemic population: the Tehran lipid and glucose study.

BACKGROUND: Elevated fasting plasma glucose (FPG) and 2-hour post-challenge glucose (2hPG) levels are known to be independent risk factors for cardiovascular disease (CVD). However, there is limited data on the association of the difference between these measures and the risk of CVD. This study aims to investigate this association in normoglycemic Iranian adults, particularly in those with low-normal FPG levels. METHODS: This prospective cohort study included 4,594 30-65-year-old participants from the Tehran Lipid and Glucose Study. Using multivariable Cox proportional hazards regression models adjusting for age, sex, body mass index, hypertension, hypercholesterolemia, smoking, education level and FPG, hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated for the association between 2hPG-FPG, both as continuous and categorical variables, and the CVD risk. Analyses of receiver operating characteristic curves were undertaken to determine the optimal 2hPG-FPG cut-off value. RESULTS: During a median of 17.9 years of follow-up, 459 CVD events occurred. A one-unit increase in 2hPG-FPG was significantly associated with an elevated risk of cardiovascular disease in both normoglycemic (HR 1.10, 95% CI (1.01-1.19)) and low-normal FPG individuals (HR 1.16, 95% CI (1.04-1.30)); this association resisted adjustment for Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) among normoglycemic individuals. However, those with 2hPG levels greater than FPG levels had a non-significant increased risk of incident CVD compared to those with 2hPG levels of less than or equal to FPG, with corresponding HR values of 1.18 (95% CI: 0.95-1.46) in normoglycemic and 1.32 (95% CI: 0.98-1.79) in low-normal FPG, respectively. For incident CVD, the optimal cut-off value for the 2hPG-FPG was found to be 1.06 mmol/L, which was applicable for both normoglycemic and low FPG populations; using this criterion, the corresponding risks for incident CVD were 1.36 (95% CI: 1.12-1.64) and 1.57 (95% CI: 1.22-2.03), respectively. CONCLUSIONS: The difference between 2hPG and FPG levels within the normoglycemic range is related to an increased risk of CVD, an issue that was independent of HOMA-IR. A cut-off point for 2hPG-FPG > 1.06 mmol/L may stratify persons at higher risk. These findings were particularly notable in those with low-normal FPG.

Association of ideal cardiovascular health metrics with incident low estimated glomerular filtration rate: More than a decade follow-up in the Tehran Lipid and Glucose Study (TLGS).

AIMS: To evaluate the association between ideal cardiovascular health metrics (ICVHM) and incident low estimated glomerular filtration rate (eGFR) among the Iranian population. METHODS: The study population included 6927 Iranian adults aged 20-65 years (2942 male) without prevalent low eGFR [i.e., eGFR < 60 ml/min/1.73 m2] and free of cardiovascular disease. The ICVHM was defined according to the 2010 American Heart Association. The multivariable Cox proportional hazards regression analysis was used to calculate the hazard ratios (HRs) of ICVHM both as continuous and categorical variables. RESULTS: Over the median of 12.1 years of follow-up, we found 1259 incident cases of low eGFR among the study population. In this population, ideal and intermediate categories of body mass index (BMI) and blood pressure (BP) and only the ideal category of fasting plasma glucose (FPG) significantly decreased the risk of developing low eGFR; the corresponding HRs and (95% confidence intervals) were (0.87, 0.77-0.99), (0.84, 0.76-0.99), (0.79, 0.68-0.93), (0.70, 0.60-0.83) and (0.76, 0.64-0.91). Also, one additional ICVHM was associated with a reduced risk of low eGFR for the global (0.92, 0.88-0.97) and biological cardiovascular health (0.88, 0.82-0.93) in these participants. A sensitivity analysis using the interval-censoring approach demonstrated that our method is robust, and results remained essentially unchanged. In a subgroup population with dietary data (n = 2285), we did not find the beneficial impact of having intermediate/ideal categories of nutrition status compared to its poor one on incident low eGFR. CONCLUSION: We found a strong inverse association between having higher global ICVHM with incident low eGFR among the non-elderly Iranian population; the issue is mainly attributable to normal BP, BMI, and FPG levels.

A prospective study on the relationship between polycystic ovary syndrome and age at natural menopause.

OBJECTIVE: This study aimed to determine whether polycystic ovary syndrome (PCOS) was associated with age at menopause, compared with women without PCOS, after adjusting for potential confounders. METHODS: A total of 1,696 reproductive-aged participants from the Tehran Lipid and Glucose Study were included in this population-based prospective study with a follow-up of approximately 20 years. Of these, 348 women with PCOS based on the Rotterdam criteria and 1,348 non-PCOS controls were followed to assess the age at which they reached menopause. An accelerated failure time survival regression model was used to identify the association between PCOS and the age at natural menopause (ANM), with and without adjustment for potential confounders. RESULTS: The unadjusted accelerated failure time survival model revealed a significant positive association between PCOS and ANM; PCOS women experienced time to menopause by a factor of 1.05 than non-PCOS controls (95% confidence interval, 1.02-1.06; P < 0.001). After adjusting for age at baseline, menarche age, history of hypertension, history of type 2 diabetes mellitus, parity, oral contraceptive use, body mass index, education level, physical activity, and smoking, the results remained significant (time ratio: 1.03; 95% confidence interval, 1.01-1.06; P = 0.002). CONCLUSIONS: This study indicates that ANM is significantly associated with PCOS in women. Our study findings may have implications for the fertility and reproductive health of women with PCOS. However, further large longitudinal studies on diverse populations accounting for other relevant confounders are still needed to provide data on the actual difference in age at menopause and to elucidate the underlying mechanisms of this association.

To what extent the weight changes impact the risk of hypertension among menopausal women: insights from Tehran lipid and glucose study.

BACKGROUND & AIM: The association between weight change and incident hypertension (HTN) in menopausal women has not been well characterized. This study aimed to determine whether weight changes after menopausal years make a difference in incidents of hypertension. MATERIALS & METHODS: This population-based study was performed using data collected from Tehran Lipid and Glucose Study cohort (1999-2018). Women who had natural and early menopause were followed up every 3 years. Data gathering was performed through the standard protocol of the study. Statistical analysis was performed using multivariable Cox hazard regression analysis. We used the 'survival' package in the R software version 3.6.0 to fit survival models. RESULTS: A total of 487 menopausal women met the inclusion criteria; 62.6% had natural menopause and remained had early menopause. Among the participants, 65.5% experienced HTN. The highest proportion of participants had > 5% weight gain, while the lowest had 3-5% weight gain. Either losing body weight (lost > 5%: HR: 0.44; CI 95%, 0.32, 0.62; p < 0.001), (lost 3-5%; HR: 0.47; CI 95%, 0.26, 0.84; p = 0.01), and weight gain > 5% (HR: 0.69; CI 95%, 0.51, 0.91; p = 0.01), were associated with decreased risk of HTN after adjustment for confounders. In this study, weight loss and gain have a protective impact on the development of HTN in subjects. For incident HTN, age (HR: 1.04 (1.01, 1.08), p = 0.004), fasting blood glucose (HR: 1.01, CI 95%:1.00, 1.01; p < 0.001), body mass index (1.02 (1.00, 1.05), p = 0.03) and smoking (1.70 (1.11, 2.58), p = 0.01) were positively associated with HTN. CONCLUSIONS: Our study indicates the significant association of weight change with hypertension risk in later life among menopausal women.

The Tehran longitudinal family-based cardiometabolic cohort study sheds new light on dyslipidemia transmission patterns.

Dyslipidemia, as a metabolic risk factor, with the strongest and most heritable independent cause of cardiovascular diseases worldwide. We investigated the familial transmission patterns of dyslipidemia through a longitudinal family-based cohort, the Tehran Cardiometabolic Genetic Study (TCGS) in Iran. We enrolled 18,729 individuals (45% were males) aged > 18 years (mean: 38.15 (15.82)) and observed them over five 3-year follow-up periods. We evaluated the serum concentrations of total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol with the first measurement among longitudinal measures and the average measurements (AM) of the five periods. Heritability analysis was conducted using a mixed-effect framework with likelihood-based and Bayesian approaches. The periodic prevalence and heritability of dyslipidemia were estimated to be 65.7 and 42%, respectively. The likelihood of an individual having at least one dyslipidemic parent reveals an OR = 6.94 (CI 5.28-9.30) compared to those who do not have dyslipidemic parents. The most considerable intraclass correlation of family members was for the same-sex siblings, with ICC ~ 25.5%. For serum concentrations, heritability ranged from 33.64 to 60.95%. Taken together, these findings demonstrate that familial transmission of dyslipidemia in the Tehran population is strong, especially within the same-gender siblings. According to previous reports, the heritability of dyslipidemia in this population is considerably higher than the global average.

Low-carbohydrate dietary score and the incidence of metabolically unhealthy phenotype based on BMI status: a cohort study.

There is scarce research focusing on the relationship between the low-carbohydrate dietary score and the development of a metabolically unhealthy phenotype. Therefore, this cohort study was designed to assess the association between the low-carbohydrate dietary score and the risk of metabolically unhealthy phenotypes (MUP). This study included 1299 adults with healthy metabolic profiles who were followed for 5.9 years. Results indicated an inverse association between the second tertile of the low-carbohydrate dietary score and the risk of developing metabolically unhealthy obesity (MUO) (HR: 0.76, 95% CI: 0.59-0.98). In addition, we found an inverse association between the healthy low-carbohydrate dietary score and the risk of MUO (HR: 0.77, 95% CI: 0.60-0.99). Our results revealed a nonlinear inverse association between the low-carbohydrate dietary score and the risk of MUP only in subjects with overweight or obesity. This relationship was independent of animal protein and fat intake. Also, we found that a lower intake of unhealthy carbohydrates was associated with a lower risk of MUP only in subjects with overweight or obesity.

Macronutrients quality indices and risk of metabolic syndrome and its components in Iranian adults.

BACKGROUND/AIM: Evidence from recent studies suggested that the quality of dietary macronutrients can play a possible role in predicting the risk of metabolic disorders. In the current study, we aimed to assess the association of carbohydrate quality index (CQI) and protein score with the risk of metabolic syndrome (MetS) in Iranian adults. METHODS: This prospective study was conducted within the framework of the Tehran Lipid and Glucose Study on 1738 individuals aged between 40 and 70 years old, who were followed up for a mean of 6.1 years. A food frequency questionnaire was used to determine CQI and protein scores. The multivariable adjusted Cox regression model was used to calculate the hazard ratio (HR) of MetS across quartiles of protein score and CQI, and its components. RESULTS: The mean ± standard deviation (SD) age and body mass index of the study population (42.5% men) were 49.3 ± 7.5 years and 27.0 ± 4.0 kg/m2, respectively. Mean ± SD scores of CQI and protein for all participants were 12.6 ± 2.4 and 10.3 ± 3.5, respectively. During the study follow-up, 834(48.0%) new cases of MetS were ascertained. In the multivariable-adjusted model, the risk of MetS was decreased across quartiles of CQI (HR = 0.83;95%CI:0.69-1.00, Ptrend=0.025) and protein score (HR = 0.75; 95% CI:0.60-0.94, Ptrend=0.041). Also, Of CQI components, the whole grain/total grains ratio showed a significant inverse association with the risk of MetS (HR = 0.75;95%CI:0.60-0.94, Ptrend=0.012). CONCLUSION: Our findings revealed that a dietary pattern with higher CQI and protein score may be related to a reduced risk of MetS in adults.