Impact of optimal cholesterol levels on subclinical atherosclerosis in the absence of risk factors in young adults.

BACKGROUND AND AIMS: We aimed to assess the association of blood lipids with the prevalence, incidence, and progression of subclinical atherosclerosis among young individuals without dyslipidemia and other traditional cardiovascular risk factors (CVRFs). METHODS: A total of 1270 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study aged 32-46 years free of cardiovascular disease, diabetes, hypertension, current smoking, and dyslipidemia (total cholesterol [TC] ≥ 240 mg/dL, triglycerides [TG] ≥ 150 mg/dL, low-density lipoprotein cholesterol [LDL-C] ≥ 160 mg/dL, high-density lipoprotein cholesterol [HDL-C] < 40 mg/dL, or taking lipid-lowering medications) were included. A subgroup with optimal lipids within the low-CVRF group was defined with TC < 200 mg/dL, LDL-C < 100 mg/dL, non-HDL-C < 130 mg/dL, and women with HDL-C ≥ 50 mg/dL. RESULTS: 1-SD higher TC (25.9 mg/dL), LDL-C (24.7 mg/dL), and non-HDL-C (26.6 mg/dL) were associated with a greater risk of presence (hazard ratios: 1.30-1.36), incidence (1.30-1.32), and progression (1.31-1.35) of coronary artery calcium (CAC) and a 42-44% greater odds of composite mean carotid intima-media thickness (CIMT) ≥ 75th percentile [780 µm] (p < 0.05). Repeating the analyses in a subset of participants with a CAC score of zero did not alter the association of TC, LDL-C, and non-HDL-C with CIMT. In the subgroup with optimal lipids, these lipid indices remained associated with an increased risk of presence and incidence of CAC and greater CIMT measures. CONCLUSIONS: Among adults aged 32-46 years, in the absence of traditional CVRFs, elevated cholesterol levels, even within what is considered optimal, are associated with atherosclerosis and arteriopathy.

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.

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.

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.

Neglected Adrenal Hypoplasia Congenita in Two Siblings with Novel Genetic Mutations in NR0B1 Gene and Notable Clinical Course: A Case Report.

BACKGROUND: Adrenal Hypoplasia Congenita (AHC) is a rare subtype of primary adrenal insufficiency (PAI) that can go undiagnosed easily. In this article, we report two brothers with hypogonadotropic hypogonadism and novel mutations in the NR0B1 gene who were misdiagnosed and mismanaged as having congenital adrenal hypoplasia (CAH) for several years. CASE PRESENTATION: Herein, we describe two brothers with similar histories; first, they were diagnosed with CAH and treated for that; however, after several years, they showed symptoms of lack of testosterone despite receiving CAH treatment. Low levels of testosterone and LH were detected in both, and a genetic test of CAH was negative for the first brother. Thereafter, DAX- 1 deficiency was suspected, and their genetic tests (the NR0B1 gene) confirmed the diagnosis of DAX-1. CONCLUSION: The diagnosis of CAH in case of low levels of 17- OHP, testosterone, and LH, as well as central hypogonadotropic hypogonadism, should be studied, and further investigations are mandatory to evaluate other subtypes of PAI, especially AHC.

Impact of coronary artery calcium on mortality and cardiovascular events in metabolic syndrome and diabetes among younger adults.

AIMS: Whether coronary artery calcium (CAC) testing in younger individuals with metabolic syndrome (MetS) and diabetes mellitus (DM) helps predict cardiovascular disease (CVD) and death independent of traditional risk factors (RFs) remains less clear. METHODS AND RESULTS: We pooled data obtained from 5174 individuals aged 38-55 years from the CARDIA (Coronary Artery Risk Development in Young Adults; n = 3047, year 20) and MESA (Multi-Ethnic Study of Atherosclerosis; n = 2127, Visit 1) studies who completed computed tomography of CAC. The mean age (SD) of participants (44.7% men) was 47.3 (4.2) years. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of CVD, coronary heart disease (CHD), and all-cause death. There were 1085 participants (21.0%) with prevalent CAC at baseline. A total of 461 (8.9%) had DM, 1025 (19.8%) had MetS without DM, and 3688 (71.3%) had neither condition. Over a median follow-up of 14.2 years, 256 (5.0%) participants died, and 304 (5.9%) CVD and 188 (3.6%) CHD events occurred. The CAC score was independently associated with incident CVD in those with DM (HR: 95% CI; 1.22: 1.08-1.38), MetS (1.18: 1.08-1.31), and neither condition (1.36: 1.26-1.46). The corresponding HRs for CAC ≥ 100 were 2.70 (1.25-5.83), 3.29 (1.87-5.79), and 6.30 (4.02-9.86), respectively. Similar associations for CHD and death were found. The impact of CAC ≥ 100 on CVD and CHD was lower in the presence of DM (P interaction < 0.05). The association of CAC with all outcomes in individuals with DM remained significant after adjusting with haemoglobin A1c levels. CONCLUSION: Coronary artery calcium score is independently associated with cardiovascular events and death over nearly 15 years after screening at ages 38-55 years, with a less pronounced impact on CVD and CHD events in the presence of DM.

In this pooled cohort, we aimed to analyse the relationship between coronary artery calcium (CAC) and incidence of cardiovascular disease (CVD), coronary heart disease (CHD), and all-cause mortality among younger individuals with diabetes mellitus (DM), metabolic syndrome (MetS), and neither condition. The CAC score was independently associated with incident CVD, CHD, and all-cause mortality in those with DM, MetS, and neither condition. The impact of CAC ≥ 100 on CVD and CHD events was lower in the presence of DM. The association of CAC with all outcomes in individuals with DM remained significant after adjusting with haemoglobin A1c levels.

The impact of obesity on different glucose tolerance status with incident cardiovascular disease and mortality events over 15 years of follow-up: a pooled cohort analysis.

BACKGROUND: The effect of obesity in different glucose tolerance statuses i.e. normoglycemia (NGT), pre-diabetes, and type 2 diabetes (T2DM) on cardiovascular disease (CVD) and mortality has been an area of ongoing debate and uncertainty. In the present study, we aimed to examine the impact of being obese, whether general or central separately, in comparison with non-obese in different glucose tolerance statuses on the above outcomes. METHODS: The study population included 18,184 participants aged 30-60 years (9927 women) from three longitudinal studies, including Atherosclerosis Risk in Communities, Multi-Ethnic Study of Atherosclerosis, and Tehran Lipid and Glucose Study. Glucose tolerance status was defined as NGT (fasting plasma glucose < 5.55 mmol/L), pre-diabetes (5.55-7.00 mmol/L), and T2DM (≥ 7 mmol/L or taking any medication for diabetes). Moreover, general and central obesity were defined based on body mass index and waist circumference (WC), respectively. Multivariable stratified Cox regression analysis was used to estimate hazard ratios (HRs (95% CI)) for CVD and mortality events. RESULTS: During a 16-year follow-up, 2733 CVD events, 1101 CV mortality, and 3678 all-cause mortality events were recorded. We observed that being generally obese in comparison with non-obese increased the risk of CV and all-cause mortality in all glucose tolerance statuses; while considering CVD events, only among individuals with T2DM, the presence of general obesity was associated with marginally significant higher risk [1.19 (0.98-1.43); p-value = 0.07]. Regarding central adiposity, multivariate analysis revealed that elevated WC in NGT participants is associated with incident CVD [1.27(1.12-1.46)] and all-cause mortality [1.13(1.00-1.28)]. Moreover, central adiposity increased the risk of CV mortality in pre-diabetes individuals [1.47 (1.11-1.95)]. CONCLUSION: Findings from this pooled prospective cohort studies provide evidence that general obesity shows an unfavorable association with CV and all-cause mortality among the general population irrespective of their glucose tolerance statusThe findings imply that it's important to take into account the requirement and magnitude of weight reduction in people who are obese when offering guidance.

The association between metabolic syndrome and insulin resistance with risk of cardiovascular events in different states of cardiovascular health status.

AIMS/INTRODUCTION: The aim was to examine the joint effect of metabolic syndrome (MetS) and insulin resistance (IR) with ideal cardiovascular health (iCVH) status on incident cardiovascular diseases (CVDs). MATERIALS AND METHODS: The study included 6,240 Iranian adults ≥30 years, free of prior cardiovascular disease. Ideal cardiovascular health was determined based on American Heart Association's Life Simple 7. Metabolic syndrome was defined according to the Joint Interim Statement Criteria, and insulin resistance was defined as HOMA-IR ≥1.85 in women and ≥2.17 in men. Multivariable Cox proportional hazard ratios (HRs) were applied to examine the impact of metabolic syndrome, and insulin resistance at various levels of iCVH status. RESULTS: During the median follow-up of 14.0 years, 909 cases of cardiovascular disease occurred. Metabolic syndrome and insulin resistance were significantly associated with incident cardiovascular disease events. In the poor and intermediate status, metabolic syndrome increased cardiovascular disease events with HRs of 1.83 and 1.57, respectively; the corresponding values for insulin resistance in the mentioned categories were 1.91 and 1.25, respectively (P values < 0.05). In the intermediate and poor iCVH status, hypertriglyceridemia was linked to a 40% and 35% higher risk of cardiovascular disease, the corresponding values for low HDL-C was 20% and 60%, respectively (P values < 0.05). Although adding metabolic syndrome, its dyslipidemia and insulin resistance to iCVH status in both poor and intermediate status significantly improve the prediction of cardiovascular disease using net reclassification improvement (P values < 0.05), the value of C-index did not change. CONCLUSIONS: Metabolic syndrome and the dyslipidemia component had a negligible but significant improvement in the prediction of cardiovascular disease among individuals with non-optimal iCVH status.

Rapid decline of kidney function increases fracture risk in the general population: Insights from TLGS.

BACKGROUND: Although the association between Chronic Kidney Disease (CKD) and all-cause fractures was addressed in previous studies, the association between estimated glomerular filtration rate (eGFR) decline and fractures was poorly addressed. For the first time we examined the association between rapid kidney function decline (RKFD) and fracture incidence among Iranian general population. METHODS: In a Tehranian community-based cohort, RKFD was defined as a 30 % decline in eGFR over 2-3 years. Cox proportional hazards models, adjusted for age, sex, current eGFR, diabetes mellitus, hypertension, dyslipidemia, current smoking, obesity status, waist circumference, prevalent cardiovascular diseases, aspirin, steroid use, education level, and marital status, were used to examine the association of RKFD with different fracture outcomes. RESULTS: Among 5305 (3031 women) individuals aged ≥30 years, during the median follow-up of 9.62 years, 226 fracture events were observed. The multivariable hazard ratio of RKFD for any-fracture events, lower-extremity, and major osteoporotic fractures were 2.18 (95 % CI, 1.24-3.85), 2.32 (1.15-4.71), and 2.91 (1.29-6.58), respectively. These associations remained significant after accounting for the competing risk of death. The impact of RKFD on the development of incident all-cause fractures was not modified by gender [men: 2.64 (1.11-6.25) vs. women: 2.11 (1.00-4.47)] and according to current CKD status [without CKD: 2.34 (1.00-5.52) vs. with CKD: 2.59 (1.04-6.44)] (all P for interaction >0.5). CONCLUSIONS: RKFD can increase the incidence of fractures among general population, the issue that was equally important among non-CKD individuals, emphasizing the need for early identification and management in those with rapidly declining eGFR.

The association of ideal cardiovascular health metrics and incident hypertension among an urban population of Iran: a decade follow-up in Tehran Lipid and Glucose Study.

We aimed to determine the association between ideal cardiovascular health metrics (ICVHM) and the incidence of hypertension among Iranian adults. The study population included 5409 Iranian adults aged ≥20 years (2088 men) without hypertension (applying the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline) at baseline. The ICVHM was defined according to the AHA's 2020 impact goals, excluding total cholesterol was replaced by non-HDL cholesterol (non-HDL-C). Multivariable Cox proportional hazards regression analysis was done to estimate the hazard ratios (HRs) for ICVHM both as continuous and categorical variables. During a median 8.5-year follow-up, 2972 new cases of hypertension were identified (men: 1,287). Non-HDL-C < 130 mg/dL in men [HR (95% CI): 0.75(0.65-0.86)] and fasting plasma glucose(FPG) < 100 mg/dL in women[HR (95% CI): 0.79(0.64-0.97)], and among both genders, being normal/overweigth status (compared to obese) and blood pressure <120/80 mmHg were associated with a lower risk for hypertension. Additionally, in both gender, a 1-point increase in the number of global ICVHM decreased the risk of hypertension by more than 10%, and having ≥5 vs. <2 ICVHM, were associated with a lower risk of hypertension by 30% (all p values < 0.05). Applying the JNC 7 guideline, the association between ICVHM, with incident hypertension, were generally similar. Having a higher number of ICVHM was associated with a lower risk of incident hypertension, using both 2017 ACC/AHA and JNC 7 guidelines, mostly attributable to keeping the ideal status of body mass index, non-HDL-C, and FPG.

Association between dietary antioxidants intake and the risk of type 2 diabetes mellitus in a prospective cohort study: Tehran Lipid and Glucose Study.

The present prospective cohort study aimed to determine whether dietary antioxidants were associated with incident type 2 diabetes mellitus (T2DM). Another objective was to find out whether such associations could be modified by the BMI status. A total of 2188 Tehranian adults aged 21-84 years, free of T2DM with the validated FFQ, was entered in the study. Multivariable Cox proportional hazards models adjusting for confounders were used to assess the association between dietary antioxidants and incident T2DM in total population, as well as in subjects with various BMI statuses. During 8·9 (8·1-9·6) years of follow-up, dietary vitamin E significantly decreased the incident T2DM, after adjustment for confounders. However, other dietary antioxidants were not shown to be significantly associated with incident T2DM. The interaction between dietary vitamin E, Mg and BMI status was found to influence the risk of T2DM (Pfor interaction < 0·05). After stratification of subjects based on BMI status, it was found that vitamin E and Mg decreased the risk of T2DM only among normal-weight individual. Also, an inverse association was found among dietary vitamin C, dietary Zn and the risk of T2DM in individuals with normal weight but not in overweight and obese individuals; however, the interaction test tended to be significant for these dietary variables. Dietary antioxidants including vitamin E, vitamin C, Zn and Mg when accompanied by healthy weight, may bring benefits to the prevention of T2DM.

Gender differences in midlife to later-life cumulative burden and variability of obesity measures and risk of all-cause and cause-specific mortality.

BACKGROUND/OBJECTIVES: Previous studies have reported the gender-specific association between general and central obesity measures, using snapshot assessments, and mortality events. This study seeks to further explore this link by examining how the longitudinal cumulative burden and variability of obesity measures from midlife to later-life impact mortality events in the Atherosclerosis Risk in Communities (ARIC) study population, specifically in relation to gender differences. SUBJECTS/METHODS: Using data from the ARIC study, a total of 7615 (4360 women) participants free of cardiovascular disease, cancer, and early mortality events were included in the data analysis. Longitudinal cumulative burden (estimated by the area under the curve (AUC) using a quadratic mixed-effects method) and variability (calculated according to average successive variability (ASV)) were considered as exposures, separately and all together. Cox proportional hazard regression models were used to estimate multivariable-adjusted standardized hazard ratios. RESULTS: The mean age was 62.4 and the median follow-up was 16.9 years. In men, AUCs of waist-related obesity measures, and also ASVs of all obesity measures were associated with increased all-cause mortality risk. In women, waist circumference and waist-to-height ratio AUCs were associated with increased all-cause mortality risk. Regarding cardiovascular mortality, all adiposity measures ASVs in both genders and waist-related obesity measures AUCs in men were associated with increased risk. Significant gender differences were found for the associations between cumulative and variability of waist-to-hip ratio for all-cause mortality and all adiposity measures ASVs for cardiovascular mortality risk with higher impact among men. CONCLUSIONS: Cumulative burden and variability in general and central obesity measures were associated with higher all-cause and cardiovascular mortalities among men. In women, general obesity measures variability, as well as cumulative and variability of central adiposity measure, increased all-cause mortality risk.

Cumulative Blood Pressure in Early Adulthood and Coronary Artery Calcium and Carotid Intima-Media Thickness in Middle Age Among Adults With Maintained Blood Pressure of <130/80 mm Hg: A Post Hoc Analysis.

BACKGROUND: To examine the association of blood pressure (BP) levels with coronary artery calcium and carotid intima-media thickness (CIMT) in people with maintained BP below the hypertension range based on current definitions. METHODS AND RESULTS: In this post hoc analysis of the CARDIA (Coronary Artery Risk Development in Young Adults) prospective observational cohort study conducted in 4 US cities, we examined 1233 study participants (mean [SD] age at year 20 examination was 45.3 [3.5] years; 65.4% women). Participants with BP assessments across 20 years and untreated BP of <130/80 mm Hg were included. Multivariable logistic or linear regression models, adjusted for age, sex, race, education, diabetes, body mass index, serum creatinine, smoking, alcohol intake, physical activity, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides, were used to examine the associations between cumulative BP measures with coronary artery calcium and CIMT. Higher long-term cumulative systolic BP and pulse pressure across early adulthood were associated with higher CIMT (both P<0.001) but not coronary artery calcium in the multivariable-adjusted model. The associations remained significant even after adjustment for a single BP measurement at year 0 or year 20. The odds ratio (OR) of a maximal CIMT >1.01 mm was ≈50% higher per 1-SD increase in systolic BP (OR, 1.50 [95% CI, 1.19-1.88]) and pulse pressure (OR, 1.46 [95% CI, 1.19-1.79]). Similar findings for CIMT were observed among individuals with a coronary artery calcium score of 0 as well as those with maintained BP of <120/80 mm Hg throughout young adulthood. CONCLUSIONS: Long-term cumulative systolic BP and pulse pressure across early adulthood within the nonhypertensive range were associated with adverse midlife alterations in CIMT.

Sex differences in risk factors for coronary heart disease events: a prospective cohort study in Iran.

We investigated sex-specific associations and their differences between major cardiovascular risk factors and the risk of incident coronary heart disease (CHD) and hard CHD (defined as nonfatal myocardial infarction and CHD death). A total of 7518 (3377 men) participants from the Tehran Lipid and Glucose Study were included. Cox models were used to estimate the hazard ratios (HRs) and women-to-men ratios of HRs for CHD events associated with each risk factor. During 20 years of follow-up (1999-2018), 1068 (631 men) and 345 (238 men) new cases of CHD and hard CHD, respectively, were documented. In total population, the incidence rates per 1000 person-years were 9.5 (9.0-10.1) and 2.9 (2.6-3.2) for CHD and hard CHD, respectively. Hypertension, diabetes, pre-diabetes, and a high waist-to-hip ratio (WHR) were associated with a greater HR of hard CHD in women than men; the women-to-men HRs were 2.85 [1.36-5.98], 1.92 [1.11-3.31], 2.04 [1.09-3.80] and 1.42 [1.10-1.82], respectively. Diabetes was associated with a higher HR of CHD in women than men (ratio of HRs 1.49 (1.10-2.01). In conclusion, we found that hypertension, diabetes, pre-diabetes, and high WHR conferred a greater excess risk of CHD events in women than in men, suggesting that Iranian women may require greater attention for the prevention of CHD events.

Association between estimated glomerular filtration rate slope and cardiovascular disease among individuals with and without diabetes: a prospective cohort study.

BACKGROUND: Previous studies have reported an association between a significant decline in estimated glomerular filtration rate (eGFR) over time and an increased risk of cardiovascular disease (CVD). This study aimed to investigate the association between the eGFR slope and CVD among individuals with and without diabetes. METHODS: This prospective cohort study was conducted within the Tehran Lipid and Glucose Study (TLGS) framework. We studied 6919 adults aged 20-70 years, including 985 with diabetes and 5934 without diabetes. The eGFR slope was determined based on repeated measurements of eGFR through linear mixed-effects models. A multivariable Cox proportional hazard model was employed to evaluate the association between eGFR slope, both in continuous and categorical form, and the risk of CVD. RESULTS: The slopes of eGFR exhibited a bell-shaped distribution, with a mean (standard deviation (SD)) of -0.63 (0.13) and - 0.70 (0.14) ml/min per 1.73 m2 per year in individuals with and without diabetes, respectively. During a median follow-up of 8.22 years, following the 9-year eGFR slope ascertainment period, a total of 551 CVD events (195 in patients with diabetes) were observed. Among individuals with diabetes, a steeper decline in eGFR slope was significantly associated with a higher risk of CVD events, even after adjusting for baseline eGFR, demographic factors, and traditional risk factors for CVD; slopes of (-1.05 to -0.74) and (-0.60 to -0.52) were associated with 2.12 and %64 higher risks for CVD, respectively, compared with a slope of (-0.51 to 0.16). Among individuals without diabetes, the annual eGFR slope did not show a significant association with the risk of CVD. CONCLUSION: Monitoring the eGFR slope may serve as a potential predictor of CVD risk in individuals with diabetes.

Resting heart rate and the risk of incident type 2 diabetes mellitus among non-diabetic and prediabetic Iranian adults: Tehran lipid and glucose study.

BACKGROUND: Resting heart rate (RHR) has been found to be a potential risk factor for developing type 2 diabetes mellitus (T2DM), with a highly significant heterogeneity among previous studies. Therefore, we examined the association of RHR and risk of incident T2DM among non-diabetic and prediabetic adults. METHODS: The study population included 2431 men and 2910 women aged ≥ 20 years without T2DM at baseline (2001-2005). Participants were followed for incident T2DM by about 3-year intervals up to April 2018. The multivariable Cox proportional models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). The models were adjusted for age, body mass index, waist circumference, educational level, physical activity, smoking, hypertension, family history of diabetes, triglycerides/ high-density lipoprotein cholesterol ratio, and fasting plasma glucose. RESULTS: During a median follow-up of 12.2 years, 313 men and 375 women developed T2DM. Interestingly, a significant sex-difference was found (all P-values for sex interaction < 0.025). Among men, compared to the first quintile (< 68 bpm: beats per minute), those who had RHR of over 84 bpm were at higher T2DM risk with a HR (95%CI) of 1.69 (1.16-2.47). Furthermore, considering RHR as a continuous variable, an increase of 10 bpm caused 17% significantly higher risk among men with a HR of 1.17 (1.05-1.30). However, among women, there was no significant association between incident T2DM and RHR. Moreover, among prediabetic participants at baseline, the association of RHR and risk of T2DM progression was generally similar to the general population, which means higher RHR increased the risk of T2DM development only among men with a HR of 1.26 (1.09-1.46) for 10 bpm increase. CONCLUSIONS: Among men, being either non-diabetic or prediabetic at baseline, higher RHR can be associated with incident T2DM; however, women didn't show a significant association. Further studies are needed to determine the added value of RHR as a potential modifiable risk factor in screening and risk prediction of incident T2DM.

Cumulative burden and trajectories of body mass index and blood pressure from childhood and carotid intima-media thickness in young adulthood.

There are significant gaps in understanding of the association between levels and rate of change of body mass index (BMI) and blood pressure (BP) at different ages during childhood and carotid intima-media thickness (CIMT) in adulthood. We investigated the association between trajectories of BMI and BP from childhood to adulthood and adult CIMT among Iranian participants in the Tehran Lipid and Glucose Study (TLGS) cohort. A total of 1334 participants (692 men), from the TLGS cohort (1999-2018) with repeated measurements of BMI and BP (2-6 times) from childhood (3-18 years) to young adulthood (20-40 years) were selected. Trajectory parameters included levels and linear slopes of BMI and BP growth curve models, and cumulative burden defined as the area under those curves (AUC). After adjusting for confounders, AUC of BMI and diastolic blood pressure (DBP) were significantly associated with high CIMT in adulthood, with the standardized odds ratios (OR) and 95% confidence interval (95% CI) of 1.35 (1.12-1.62) and 1.27 (1.01-1.60), respectively. Associations between level-independent slopes of BMI and adult CIMT were significantly positive (ORs: 1.27 to 1.26) during childhood ages (3-18 years). Further, levels of BMI (ORs: 1.23 to 1.29) and DBP (ORs: 1.25 to 1.33) during the ages of 13-18 and 11-17 years, respectively, were significantly associated with CIMT in adulthood (all P < 0.05). The cumulative burden of BMI and DBP was associated with CIMT in adulthood. Adolescence is a crucial period for high CIMT, which has implications for early prevention of atherosclerosis.

Effect of weight change on the association between overall and source of carbohydrate intake and risk of metabolic syndrome: Tehran lipid and glucose study.

BACKGROUND: In this prospective cohort study, we aimed to evaluate the association between dietary carbohydrates, whole grains, refined grains, and simple sugar with the risk of metabolic syndrome (MetS) and assess the effect of weight change on these associations. METHODS: This study was conducted within the framework of the Tehran Lipid and Glucose Study (TLGS). We included 1915 healthy participants with complete demographic, anthropometric and dietary measurements, among whom 591 developed MetS during 8.9 years of follow-up. Intake of dietary carbohydrates, whole grains, refined grains, and simple sugar was assessed with a validated semi-quantitative food frequency questionnaire. Multivariable adjusted Cox regression was used to estimate hazard ratios (HRs) for MetS events across tertiles of dietary variables. Using joint classification, the effect of weight change on the association between dietary variables and risk of MetS was assessed by Cox regression. RESULTS: Carbohydrate intake was not associated with the risk of MetS in multivariable-adjusted models. Whole grains intake was inversely associated with the risk of MetS (HR: 0.78, CI: 0.63-0.98), while this association disappeared after adjustment for weight change. The risk of MetS increased by 11% (1.11, 1.09-1.14) for each 3% energy increment from simple sugar, and by 5% (1.05, 1.03-1.08) for each 1 serving/day increment in refined grains. Consumption of refined grains increased the risk of MetS; an effect modification of this association was found by weight change. Among subjects with weight loss, intake of refined grains < median intake decreased the risk of MetS (0.59, 0.41-0.87). However, consumption of refined grains ≥ median intake increased the risk of MetS in individuals with weight gain (1.47, 1.08-2.01). Simple sugar was positively associated with an increased risk of MetS, after adjustment for weight change (3.00, 2.37-3.82). In joint classification, intake of simple sugar greater than median intake increased the risk of MetS, independent of weight change. CONCLUSION: Our findings suggest an effect modification by weight change on the association between carbohydrates, and refined grains intake and the risk of MetS. Weight loss along with lower consumption of carbohydrates, and refined grains reduced the risk of MetS. However, simple sugar intake, regardless of weight change, was associated with an increased risk of MetS.

Kidney function decline is associated with mortality events: over a decade of follow-up from Tehran Lipid and Glucose Study.

BACKGROUND: To investigate the association between estimated glomerular filtration rate (eGFR) change and mortality risk in a cohort from the Middle East and North Africa region with increasing chronic kidney disease burden. METHODS: We included 2210 participants aged ≥ 50 years from the prospective cohort of the Tehran Lipid and Glucose Study. The interval for eGFR measurement was between the examinations in 2002-2005 to 2009-2011, and participants were followed through March 2018. Glomerular filtration rate was estimated from serum creatinine using the CKD-EPI creatinine equation. We assessed the association of rapid kidney function decline, (defined as annual eGFR decline ≥ 3 ml/min/1.73 m2 per year); ≥ 30% eGFR decline over six years; and certain drop in kidney function (≥ 25% eGFR decline plus drop in eGFR category) with mortality outcomes. RESULTS: During a median follow-up of 14.3 years after recruitment, 315 all-cause and 112 cardiovascular disease deaths were recorded. The multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause death for rapid kidney function decline, ≥ 30% decline in eGFR over 6 years, and drop in kidney function were 1.68 (1.24-2.27), 2.01 (1.46-2.78), and 1.49 (1.11-1.98), respectively. The HRs of all-cause death and for rapid kidney function decline in those without and with chronic kidney disease were 1.41 (1.03-1.91) and 3.38 (1.69-6.76), respectively. Similar findings were observed regarding cardiovascular disease-related and non-cardiovascular disease-related mortality. CONCLUSIONS: Estimated GFR decline is associated with an increased mortality risk, indicating its ability to provide additional prognostic information beyond traditional risk predictors in the general population.

Diagnostic dilemma in a patient with history of medullary thyroid carcinoma and abnormal serum liver enzymes; a case report with six years follow up.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor that originates from parafollicular C-cells. Calcitonin (Ctn) and carcinoembryonic antigen (CEA) are useful biomarkers for monitoring MTC cases. CASE PRESENTATION: Here, we describe a 48-year-old woman, who presented in 2014 with bilateral thyroid nodules. Report of fine needle aspiration was suspicious for MTC; initial laboratory evaluation showed serum Ctn level of 1567 pg/mL. After excluding type 2 multiple endocrine neoplasia syndrome clinically, total thyroidectomy and neck lymph node dissection were performed. The final histopathological diagnosis was right lobe MTC with neither vascular invasion nor lymph node involvement. On regular follow-up visits, Ctn and CEA levels have been undetectable, and repeated cervical ultrasonographic exams were unremarkable from 2014 to 2021. As liver enzymes became elevated in 2016, the patient was further evaluated by a gastroenterologist. Abdominopelvic ultrasonography revealed a coarse echo pattern of the liver parenchyma with normal bile ducts. A liver fibroscan showed a low fibrosis score (7kPa). The patient was recommended to use ursodeoxycholic acid. According to the progressive rise of liver enzymes with a cholestatic pattern in October 2020, a liver biopsy was performed that showed tiny nests of neuroendocrine-like cells with a background of primary biliary cholangitis (PBC). Immunohistochemical stainings were positive for chromogranin A (CgA), and synaptophysin and negative for Ctn, CEA, and thyroglobulin. Further imaging investigations did not reveal any site of a neuroendocrine tumor in the body. Considering normal physical exam, imaging findings, as well as normal serum levels of Ctn, CEA, CgA, and procalcitonin, the patient was managed as a PBC. CONCLUSION: In follow-up of a patient with MTC, we reported progressively increased liver enzymes with a cholestatic pattern. Liver biopsy revealed nests of neuroendocrine-like cells with a background of PBC, the findings that might suggest acquiring neuroendocrine phenotype by proliferating cholangiocytes.