Association of Anthropometric Indices With Midlife Cardiovascular Risk in Young Individuals Without Obesity and Traditional Risk Factors.

BACKGROUND: The aim of this study was to assess how early-adulthood body mass index (BMI) and waist circumference (WC) relate to long-term cardiovascular structure, function, and prognosis in individuals without obesity and with low cardiovascular risk factor (CVRF) burden. METHODS AND RESULTS: A total of 2024 participants aged 18 to 30 from the CARDIA (Coronary Artery Risk Development in Young Adults) study, without obesity and with low CVRFs defined as the absence of cardiovascular disease (CVD), diabetes, hypertension, current smoking, and dyslipidemia were included. A CVRF-optimal subgroup was also defined, with blood pressure<120/80 mm Hg, fasting glucose <100 mg/dL, total cholesterol <200, low-density lipoprotein cholesterol <130, and women with high-density lipoprotein cholesterol ≥50 mg/dL. Coronary artery calcification, carotid intima-media thickness, left ventricular mass, left ventricular ejection fraction, longitudinal peak systolic strain, and diastolic function were assessed in midlife. Cox regression was used to calculate hazard ratios of BMI and WC for all-cause death and CVD events. Logistic regression was used to estimate odds ratios for subclinical CVD. Over 33.9 years (median follow-up), 5.2% (n=105) died, and 2.6% (n=52) had CVD events. Each 1-SD BMI increase was associated with 27% (95% CI, 1.10-1.47), 24% (1.08-1.43), 42% (1.20-1.68), 28% (1.05-1.57), 51% (1.20-1.90), and 49% (1.10-2.02) higher odds of coronary artery calcification presence, increased carotid intima-media thickness, left ventricular hypertrophy, reduced left ventricular ejection fraction, low longitudinal peak systolic strain, and diastolic dysfunction, respectively, in the CVRF-low group. Generally, similar associations were found for WC and in the CVRF-optimal subgroup. No significant associations between BMI and WC with CVD and death were found. CONCLUSIONS: Elevations in BMI and WC among young low-risk individuals, even within the nonobesity range, are associated with midlife cardiovascular health.

Weight change and risk of incident type 2 diabetes: short, medium and long-term follow-up in tehran lipid and glucose study.

BACKGROUND: Despite the high burden of obesity and Type 2 diabetes (T2DM) in the Middle East/West Asia region, the effect of weight change on the development of T2DM is poorly addressed. Therefore, we aimed to assess the impact of 3-year body weight change on incident of T2DM over 3-, 6-, and 9-year periods among Iranian adults. METHODS: A total of 6930 participants (men = 2567) aged ≥ 20 years free of T2DM or cancer at baseline were included. Weight measurements were taken at baseline (2002-2005) and approximately 3 years later. Participants were categorized based on their weight change ratio into ≥ 5% loss, stable (± 5%), and ≥ 5% gain. Generalized estimating equations (GEE), adjusted with age, sex, education levels, baseline measurements of fasting plasma glucose, weight, waist circumference, triglycerides to high-density lipoprotein cholesterol ratio, family history of diabetes, current smoker, hypertension, and prevalent cardiovascular disease were applied to estimate the Odds ratios (ORs) and 95% confidence intervals (CIs) of weight change categories for incident T2DM, considering stable weight as a reference. RESULTS: During median follow-ups of 3-, 6-, and 9-year, 295, 505, and 748 cases of T2DM occurred, respectively. Weight gain of ≥ 5%, as compared to stable weight group (± 5%), was associated with increased T2DM risk, with ORs of 1.58 (95% CI 1.16-2.14), 1.76 (1.41-2.20), and 1.70 (1.40-2.05) for the 3-, 6-, and 9-year follow-ups, respectively, in multivariable analysis; corresponding values for weight loss ≥ 5% were 0.48 (0.29-0.80), 0.57 (0.40-0.81), and 0.51 (0.38-0.68), respectively. This association persisted even after adjusting for attained weight. Subgroup analysis showed consistent associations across age, gender, and body mass index categories. CONCLUSION: Weight gain and loss of ≥ 5% were associated with increased and decreased risks of incident T2DM, respectively, regardless of attained weight. This association was consistent over various follow-up durations among the Iranian population as recommended by guidelines.

Association between metabolic score for insulin resistance and clinical outcomes: insights from the Tehran lipid and glucose study.

BACKGROUND: We aimed to assess the relationship between Metabolic Score for Insulin Resistance (METS-IR) and the incidence of coronary heart disease (CHD), stroke, mortality, diabetes, hypertension, and chronic kidney disease (CKD) in a population from the Middle East and North Africa (MENA) region. METHOD: Individuals aged ≥ 20 years were enrolled. Cox proportional hazards regression models were applied to assess the association between METS-IR and incident CHD, stroke, all-cause mortality, diabetes, hypertension, and CKD. RESULTS: Over a median follow-up period of 9-18 years, 1080 (10.6%), 267 (2.6%), 1022 (9.6%), 1382 (16.4%), 2994 (58.5%), and 2002 (23.0%) CHD, stroke, all-cause mortality, diabetes, hypertension, and CKD events occurred, respectively. Compared to the lowest quartile (reference), the hazard ratios (HR) associated with the highest quartile of METS-IR were 1.527 (95% confidence interval [CI]: 1.208-1.930, P for trend 0.001), 1.393 (0.865-2.243, > 0.05), 0.841 (0.682-1.038, > 0.05), 3.277 (2.645-4.060, < 0.001), 1.969 (1.752-2.214, < 0.001), and 1.020 (0.874-1.191, > 0.05) for CHD, stroke, all-cause mortality, diabetes, hypertension, and CKD, respectively. METS-IR, as a continuous variable, was significantly associated with the risk of incident CHD [HR, 95% CI: 1.106, 1.034-1.184], diabetes [1.524, 1.438-1.616], and hypertension [1.321, 1.265-1.380]. These associations were also independent of metabolic syndrome (METS) and remained unchanged in a subgroup of individuals without METS and/or diabetes. CONCLUSIONS: Increasing levels of METS-IR were significantly associated with a greater risk of incident CHD, diabetes, and hypertension; therefore, this index can be a useful tool for capturing the risk of these clinical outcomes.

Effect of metformin (vs. placebo or sulfonylurea) on all-cause and cardiovascular mortality and incident cardiovascular events in patients with diabetes: an umbrella review of systematic reviews with meta-analysis.

Purpose: The current umbrella review aimed to evaluate the effect of metformin on all-cause mortality (ACM), cardiovascular mortality, and cardiovascular disease (CVD) incidence in DM patients. Methods: PubMed, Scopus, Cochrane, Google Scholar, and Web of Science databases were searched with special keywords. Related studies were included after screening by two independent investigators based on title and full texts. The AMSTAR2 checklist was used to assess the quality of studies, and Cochran tests were used to assess the heterogeneity between studies. Overall, seventeen systematic reviews and meta-analysis studies were included. The results revealed that the risk of ACM in patients who received metformin was lower than in patients who did not receive metformin. (OR: 0.80, 95% CI:0.744,0.855); also, the risk of CVD mortality in metformin patients was lower than in the other two groups (placebo and other anti-diabetic drugs) (OR: 0.771, 95% CI:0.688,0.853, P:0.001). The risk of CVD in metformin users was also lower than in the other two groups (OR: 0.828, 95% CI:0.781,0.785). Summary: This comprehensive review showed that the risk of ACM, death due to CVD, and incidents of CVD in DM who use metformin was lower than the patients who received a placebo only or other diabetic drugs, which can guide clinicians in medical decision-making. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01309-y.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.