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.

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.

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.

Change in blood pressure status defined by 2017 ACC/AHA hypertension guideline and risk of cardiovascular disease: results of over a decade of follow-up of the Iranian population.

Background: Hypertension (HTN) is known to be the leading cause of cardiovascular disease (CVD) and mortality. We aimed to assess the impact of changes in 3 years in different blood pressure (BP) categories on incident CVD. Methods: In this study, 3,685 Tehranians aged ≥30 years (42.2% men) free of prevalent CVD with BP level <140/90 mmHg and not on BP-lowering medications were enrolled. Participants were grouped according to baseline BP category using the 2017 ACC/AHA hypertension guideline definition: normal BP (<120/80 mmHg), elevated BP (120-129/<80), and stage 1 HTN (130-139 and/or 80-89). The hazard ratio of incident CVD by changes in the BP category was estimated after adjustment for traditional risk factors using Cox's proportional hazard model, with stable normotension as a reference. Results: During a median follow-up of 11.7 years, 346 CVD events (men = 208) occurred. Compared to the reference group, among participants with normal BP at baseline, only those with BP rising to stage 1 HTN [1.47 (0.99-2.16)], and among those with stage 1 HTN at baseline, regression to elevated BP [1.80 (1.11-2.91)], remaining at stage 1 [1.80 (1.29-2.52)], and progression to stage 2 HTN [1.81 (1.25-2.61)] had a higher risk for CVD; however, regression to normal BP attenuated this risk [1.36 (0.88-2.12)]. Conversion from elevated BP to any other categories had no significant association with CVD risk. Conclusions: Generally, prevalent stage 1 HTN (regardless of changing category) and incident stage 1 HTN were significantly associated with a higher risk of CVD; even regression to elevated BP did not attenuate the risk. Accordingly, these populations are potential candidates for antihypertensive management.

The impact of general and central obesity for all-cause hospitalization among Iranian adults: a 20 year follow-up-results from the TLGS cohort.

BACKGROUND: Few studies have examined the effect of obesity indices on total number of hospitalizations. We examined the associations between body mass index (BMI) and waist circumference (WC) and rate of all-cause hospitalizations among Iranian adult participated in the Tehran Lipid and Glucose Study cohort. METHODS: This study included 8202 individuals (3727 men) aged ≥ 30 years, who were followed for a median of 18 years. Participants were categorized into three groups according to their baseline BMI: normal weight, overweight and obese. In addition, they were classified according to WC in two categories: normal WC and high WC. Negative Binomial regression model was used to estimate the incidence rate ratios (IRRs) and 95% confidence interval (95% CI) of all-cause hospitalizations in relation to obesity indices. RESULTS: The overall crude rate of all-cause hospitalizations were 77.6 (95% CI, 73.9-81.2) and 76.9 (73.4-80.3) per 1000 person-year in men and women, respectively. The covariate adjusted rate of all-cause hospitalizations was 27% higher in obese men than normal weight men (IRR (95% CI): 1.27 (1.11-1.42)). Among women, overweight and obese individuals had 17% (1.17 (1.03-1.31)) and 40% (1.40 (1.23-1.56)) higher rate of hospitalization compared to normal weight women. Having high WC was associated with 18% (1.18 (1.08-1.29)) and 30% (1.30 (1.18-1.41)) higher rate of all-cause hospitalization in men and women, respectively. CONCLUSIONS: Obesity and high WC were associated with increased hospitalization rates during long-term follow-up. Our findings suggests that successful obesity prevention programs may decrease the number of hospitalizations, particularly, in women.

Are HOMA-IR and HOMA-B good predictors for diabetes and pre-diabetes subtypes?

BACKGROUND: To investigate the association between the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Homeostasis Model Assessment of Beta-cell function (HOMA-B) with the incidence of diabetes and pre-diabetes subtypes. METHODS: A total of 3101 normoglycemic people aged 20-70 years were included in the 6-year follow-up study. Multinomial logistic regression was used to calculate the incidence possibility of isolated Impaired Fasting Glucose (iIFG), isolated Impaired Glucose Tolerance (iIGT), Combined impaired fasting glucose & impaired glucose tolerance (CGI), and Diabetes Mellitus (DM) per standard deviation (SD) increment in HOMA-IR and HOMA-B in the crude and multivariable model. RESULTS: In the multivariate model, an increase in one SD change in HOMA-IR was associated with a 43, 42, 75, and 92% increased risk of iIFG, iIGT, CGI, and DM, respectively. There was a positive correlation between the increase in HOMA-B and the incidence of iIGT; however, after adjusting the results for metabolic syndrome components, it was inversely correlated with the incidence of iIFG [Odds Ratio = 0.86(0.75-0.99)]. CONCLUSIONS: HOMA-IR is positively correlated with diabetes and pre-diabetes subtypes' incidence, and HOMA-B is inversely correlated with the incidence of iIFG but positively correlated with iIGT incidence. However, none of these alone is a good criterion for predicting diabetes and pre-diabetes.

Three-year change in glycemic state and the future risk of incident hypertension among Iranian adults: Tehran Lipid and Glucose Study.

The impact of 3-year change in glycemic state on the risk of hypertension among Tehranian adults aged ≥20 years was assessed. The study population included 1679 men and 2348 women who were non-diabetic normotensive at enrollment. The following categories were defined both at baseline visit and three years later (second visit): normoglycemia [normal fasting glucose (NFG) and normal glucose tolerance (NGT)] and prediabetes [impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)]. Changes in the categories, i.e., regression to normoglycemia, remaining in previous status, and progression to diabetes were assessed. Changes in fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) categories were also considered separately. We used the Cox models adjusted for traditional hypertension risk factors to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). During a median follow-up of 9.4 years, 485 men and 589 women developed hypertension. Among men, considering both FPG and 2hPG, compared to individuals remaining normoglycemic, changing from prediabetes to normoglycemia had a HR of 1.30 (95% CI: 0.98-1.71; P-value: 0.064). Defining changes by 2hPG showed that compared to remaining NGT, incident IGT (progression from NGT to IGT) had a significant association with increased risk of hypertension development by a HR of 1.61 (1.13-2.30). Among women, on the other hand, change in glycemic state generally didn't show a significant association with incident hypertension. To sum up, change in glycemic state hadn't a significant association with hypertension development among women; however, compared to remaining NGT, men with incident IGT had a significant higher risk.

The relationship between glucose intolerance status and risk of hospitalization during two decades of follow-up: Tehran lipid and glucose study.

OBJECTIVE: To assess the relationship between glucose intolerance statuses at baseline defined as normal glucose tolerance (NGT), pre-diabetes, newly diagnosed (NDM) and known diabetes mellitus (KDM) and all-cause hospitalization among Iranian men and women during 20 years of follow-up. RESEARCH DESIGN AND METHODS: This study included 8,014 individuals (3,836 men) ≥30 years from the cohort of Tehran Lipid and Glucose Study. Incidence rate ratios (IRRs) and (95% confidence interval (95% CI) for three groups of pre-diabetes, NDM and KDM was estimated using the Negative Binomial regression model, considering NGT group as reference group. Regression models were adjusted for age, body mass index, hypertension, chronic kidney disease, and cardiovascular disease (CVD). RESULTS: Among men, compared with NGT group, those with pre-diabetes, NDM and KDM had higher incidence rate for hospitalization, with IRRs (95% CI) of 1.08 (0.96-1.20), 1.38 (1.20-1.57) and 1.96 (1.66-2.26), respectively, after adjusting for confounders. The corresponding values were 1.07 (0.96-1.17), 1.40 (1.21-1.59) and 2.07 (1.72-2.42) for women. Men with diabetes, generally had a higher rate of hospitalization for CVD rather than their female counterparts (IRRs: 1.46; 1.17-1.74). In patients with diabetes, the most common causes of hospitalization were macrovascular complications (i.e. coronary heart disease and stroke). Moreover, among the individuals with diabetes, those with poor glycaemic control (fasting plasma glucose (FPG) >10 mmol/l) had 39% higher rate of hospitalization than those with fair glycaemic control (FPG <10 mmol/l) (1.39; 1.12-1.65), adjusted for confounders. CONCLUSION: Pre-diabetes, NDM, and KDM were associated with increased hospitalization rates during long-term follow-up. Interventions such as lifestyle modification or pharmacological therapies aiming to slow down the pre-diabetes and fair control of diabetes might potentially decrease the rate of hospitalization.Key messagesNDM and KDM status both increased rate of all-cause hospitalization.CVD and T2DM complication were the most common cause of hospitalization among patients with diabetes.Hospitalization due to recurrent CHD was significantly higher in men with diabetes than their female counterparts.

Three-year weight change and risk of all-cause, cardiovascular, and cancer mortality among Iranian adults: over a decade of follow-up in the Tehran Lipid and Glucose Study.

BACKGROUND: We investigated the impact of weight change on mortality in a population-based cohort setting. METHODS: We conducted two weight measurements for 5436 participants aged ≥ 30 years with an approximate 3-year interval. Based on their weight change, we categorized participants to: > 5% weight loss, 3-5% weight loss, stable weight (± < 3%), 3-5% weight gain, > 5% weight gain. We followed participants for mortality annually up to March 20th 2018. We applied the multivariable Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of weight change categories for all-cause, cardiovascular (CV), and cancer mortality, considering stable weight as reference. The Cox models was adjusted for age, sex, educational level, body mass index, smoking status, hypertension, hypercholesterolemia, diabetes, and cardiovascular disease (CVD) at baseline. RESULTS: During a median follow-up of 14.4 years, 629 deaths (247 CV and 126 cancer deaths) have occurred. Over 5% weight loss and gain were associated with increased risk of all-cause mortality in multivariable analysis with HRs of 1.47 [95% CI: 1.17-1.85] and 1.27 [1.02-1.57], respectively; however, a 3-5% loss or gain did not alter the risk of all-cause mortality significantly. These significant risks for wight change > 5% were not modified by the presence of diabetes, obesity, and smoking status; however, the unfavorable impact of weight change on mortality events was more prominent in those older than > 65 years (P-value for interaction: 0.042). After excluding those with history of CVD, diabetes, and cancer during the weight measurements period, these associations significantly attenuated (HR: 1.29 [0.89-1.87] for > 5% weight loss and 1.12 [0.84-1.50] for > 5% weight gain). Additionally, a > 5% weight loss was also associated with about 60% higher risk for CV mortality (HR: 1.62 [1.15-2.28]), and a 3-5% weight loss was associated with about 95% higher risk of cancer mortality (HR: 1.95 [1.13-3.38]). CONCLUSIONS: Our findings showed a U-shaped association across weight change categories for all-cause mortality risk with over 5% weight gain and loss causing higher risk. Moreover, weight loss can have adverse impact on CV and cancer mortality events.

Ideal cardiovascular health status and risk of cardiovascular disease and all-cause mortality: over a decade of follow-up in the Tehran lipid and glucose study.

Objective: To quantify the association between ideal cardiovascular health (CVH) metrics and incident cardiovascular disease (CVD) including different subtypes [coronary heart disease (CHD), stroke, and sudden death], and all-cause mortality in an Iranian population. Methods: The study population included 6,388 participants (2,726 men) aged 48.0 ± 12.4 years free of CVD at baseline. We utilized the American Heart Association's 2020 impact target criteria of ideal, intermediate, and poor CVH. The multivariate Cox proportional Hazard model, adjusted for age, sex, educational level, marital status, and family history of CVD, was applied to estimate the hazard ratio (HR) of outcomes per one additional metric of ideal CVH metrics. Furthermore, the risk was also calculated for ideal and intermediate categories considering poor category as a reference. Results: During the median follow-up of 11.26 years, 692 CVD, 589 CHD, 130 stroke, 111 sudden death, and 519 all-cause mortality events were reported. All of the individual ideal CVH metrics were independent predictors except intermediate physical activity level for CVD, BMI < 25 kg/m2, and intermediate physical activity for all-cause mortality. Each additional metrics of ideal CVH decreased the risk by 31 (0.69, 0.65-0.73) for CVD, 32 (0.68, 0.64-0.73) for CHD, 31 (0.69, 0.60-0.80) for stroke, 25 (0.75, 0.64-0.88) for sudden death, and 13% (0.87, 0.81-0.93) for all-cause mortality events. Moreover, intermediate and ideal categories of CVH metrics were associated with lower risk for different CVD outcomes, i.e., 44 (0.56, 0.48-0.65) and 76% (0.24, 0.17-0.35) for CVD; 43 (0.57, 0.47-0.67) and 75% (0.25, 0.16-0.37) for CHD, 58 (0.42, 0.29-0.61) and 86% (0.14, 0.04-0.44) for stroke; 56 (0.44, 0.29-0.66) and 55% (0.45, 0.21-0.99) for sudden death; and 25 (0.75, 0.62-0.90) and 46% (0.54, 0.37-0.80) for all-cause mortality events, respectively. We also assessed the impact of changes in ideal CVH status from phase III to phase IV (2008-2011) on CVD events among 5,666 participants. Accordingly, compared to those remaining in the poor category, all of the changes in ideal CVH categories showed a lower risk for CVD events. Conclusion: Among the Iranian population, meeting higher ideal CVH metrics is associated with a lower risk of different CVD events and mortality outcomes.

Application of the 2017 American college of cardiology/American Heart Association Blood Pressure Guidelines for cardiovascular outcomes among Tehranian residents.

OBJECTIVES: To evaluate the associations of cardiovascular disease (CVD) outcomes with elevated blood pressure (BP), stage I of isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic diastolic hypertension (SDH), defined by 2017 ACC/AHA guidelines among the Tehranian adult population. METHOD: We enrolled 7068 residents of Tehran (district No. 13) aged at least 30 years, who were free of CVD and not taking antihypertensive medications at baseline. Participants were categorized into eight categories: normal BP (reference group), elevated BP, stage I IDH, stage I ISH, stage I SDH, and all stage II phenotypes. Significant interactions were found between age groups (<60 versus ≥60 years) and BP categories (P value: 0.017); hence, the analysis was performed in each age group, separately. We used multivariable Cox proportional regression analysis to evaluate the association of different BP categories with incident CVD. RESULTS: During 18years of follow-up, 1053 CVD events occurred. In the younger group, stage I of IDH and SDH were associated with increased CVD risk with hazard ratios (HRs) of 1.23 (95% confidence interval: 0.99-1.52) and 1.42 (1.04-1.94), respectively. In the older group, stage I of IDH had a lower risk for coronary heart disease (CHD) [HR 0.53 (0.29-0.96)]. As a sensitivity analysis, among high CVD risk individuals (10-year risk ≥10%), we found a higher risk for CVD among those with elevated BP and stage I of SDH. For individuals with 10-year risk less than 10%, all BP parameters, except stage I of IDH, were associated with increased CVD risk. Although there was no significant interaction between sex and BP categories, elevated BP and stage I of SDH significantly increased the risk of CVD only among men. CONCLUSION: Age is an important potential modifier in the association between stage I of hypertension and CVD/CHD risk. Stage I of IDH was not an alarming status for CVD development, whether the participants had a high CVD risk or not.

Reduced Sensitivity to Thyroid Hormone Is Associated with Diabetes and Hypertension.

CONTEXT: Recently, reduced sensitivity to thyroid hormone as a more common finding in the general population and its possible association with metabolic parameters has been the focus of attention. OBJECTIVE: The objective was to evaluate the cross-sectional association of thyroid hormone sensitivity with diabetes, metabolic syndrome (MetS), and its components. METHODS: The study included a Tehranian representative sample of 5124 subjects aged ≥20 years participating in the Tehran Thyroid Study (2008-2011). Body weight, waist circumference, and blood pressure (BP) were measured, and serum concentrations of lipids and lipoproteins, fasting blood glucose, insulin, free thyroxine (fT4), and thyrotropin (TSH) were assayed. Thyroid hormone resistance was calculated by the Thyroid Feedback Quantile-based Index (TFQI) and Iranian-referenced Parametric TFQI (PTFQI) and compared with 2 other indices: Thyrotroph T4 Resistance Index (TT4RI) and TSH Index. RESULTS: TFQI was significantly associated with high BP MetS criterion (OR = 1.14, 95% CI: 1.06, 1.23) and diabetes mellitus (OR = 1.16, 95% CI: 1.04, 1. 30, P = .009) in euthyroid subjects after adjusting for age, sex, smoking, physical activity, body mass index, and Homeostasis Model Assessment Index for Insulin Resistance. TFQI was not associated with new-onset diabetes contrary to known diabetes in subgroup analysis. The results were similar for PTFQI. TSHI (OR = 1.22, 95% CI: 1.08, 1.38, P = .001) and TT4RI (OR = 1.08, 95% CI: 1.01, 1.16, P < .001) were associated only with high BP in euthyroid subjects. CONCLUSION: The new TFQI index seems to be the indicator of reduced sensitivity to thyroid hormone most suitable to associate its population variations with diabetes and hypertension in euthyroid subjects; however, interpretation for diabetes should be concerned with cautions, necessitating future studies.

Clinical features, risk factors and a prediction model for in-hospital mortality among diabetic patients infected with COVID-19: data from a referral centre in Iran.

OBJECTIVES: The aim of this study was to identify risk factors of in-hospital mortality among diabetic patients infected with COVID-19. STUDY DESIGN: This is a retrospective cohort study. METHODS: Using logistic regression analysis, the independent association of potential prognostic factors and COVID-19 in-hospital mortality was investigated in three models. Model 1 included demographic data and patient history; model 2 consisted of model 1, plus vital signs and pulse oximetry measurements at hospital admission; and model 3 included model 2, plus laboratory test results at hospital admission. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were reported for each predictor in the different models. Moreover, to examine the discriminatory powers of the models, a corrected area under the receiver-operating characteristic curve (AUC) was calculated. RESULTS: Among 560 patients with diabetes (men = 291) who were hospitalised for COVID-19, the mean age of the study population was 61.8 (standard deviation [SD] 13.4) years. During a median length of hospitalisation of 6 days, 165 deaths (men = 93) were recorded. In model 1, age and a history of cognitive impairment were associated with higher mortality; however, taking statins, oral antidiabetic drugs and beta-blockers was associated with a lower risk of mortality (AUC = 0.76). In model 2, adding the data for respiratory rate (OR 1.07 [95% CI 1.00-1.14]) and oxygen saturation (OR 0.95 [95% CI 0.92-0.98]) slightly increased the AUC to 0.80. In model 3, the data for platelet count (OR 0.99 [95% CI 0.99-1.00]), lactate dehydrogenase (OR 1.002 [95% CI 1.001-1.003]), potassium (OR 2.02 [95% CI 1.33-3.08]) and fasting plasma glucose (OR 1.04 [95% CI 1.02-1.07]) significantly improved the discriminatory power of the model to AUC 0.86 (95% CI 0.83-0.90). CONCLUSIONS: Among patients with type 2 diabetes, a combination of past medical and drug history and pulse oximetry data, with four non-expensive laboratory measures, was significantly associated with in-hospital COVID-19 mortality.

Weight change and risk of cardiovascular disease among adults with type 2 diabetes: more than 14 years of follow-up in the Tehran Lipid and Glucose Study.

BACKGROUND: To examine the impact of weight change on incident cardiovascular disease and coronary heart disease (CVD/CHD) among an Iranian population with type 2 diabetes mellitus (T2DM). METHODS: The study population included 763 participants with T2DM aged ≥ 30 years without a history of CVD and cancer at baseline. Two weight measurements done at baseline and about 3 years later. Based on their weight change, they categorized into: > 5% loss, 3-5% loss, stable (± < 3%), 3-5% gain, > 5% gain. Participants were then followed for incident CVD/CHD annually up to 20 March 2018. Multivariable Cox proportional hazard models, adjusted for age, sex, body mass index, educational level, current smoking, glucose-lowering drug use, family history of CVD, hypertension, hypercholesterolemia, chronic kidney disease, and fasting plasma glucose (FPG) were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of weight change categories for incident CVD/CHD, considering stable weight as reference. RESULTS: After the weight change measurement, during a median follow-up of 14.4 years, 258 CVD and 214 CHD occurred. Over 5% weight gain was associated with reduced risks of CVD and CHD development by the HRs of 0.70 [95% CI 0.48-1.01; P-value: 0.058] and 0.61 [0.40-0.93], respectively, in multivariable analysis. After further adjustment for FPG change, the HRs of weight gain > 5% were attenuated to 0.75 [0.51-1.10; P-value: 0.138] and 0.66 [043-1.01; P-value: 0.053] for incident CVD and CHD, respectively. The effect of weight loss > 5% was in opposite direction among those older versus younger than 60 years; with suggestive increased risk (not statistically significant) of incident CHD/CVD for the older group. Moreover, weight gain > 5% significantly reduced the risk of CHD only among those older than 60 years (P-value for interaction < 0.2). Furthermore, weight gain > 5% had an association with lower risk of CVD and CHD among sulfonylurea users (0.56 [0.32-0.98] for CVD and 0.54 [0.29-0.99] for CHD). CONCLUSIONS: Our results with a long-term follow-up showed that weight gain > 5% was associated with better CVD/CHD outcomes among Iranian participants with T2DM, especially older ones. Moreover, we did not find an unfavorable impact on incident CVD/CHD for sulfonylurea-induced weight gain.

High Incidence of Chronic Kidney Disease among Iranian Diabetic Adults: Using CKD-EPI and MDRD Equations for Estimated Glomerular Filtration Rate.

BACKGROUND: To investigate the population based incidence rate of chronic kidney disease (CKD) and its potential risk factors among Iranian diabetic adults during over 14 years of follow-up. METHODS: Two different equations (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] and Modification of Diet in Renal Disease [MDRD]) were applied for the calculating the estimated glomerular filtration rate (eGFR). Among a total of 1,374 diabetic Tehranian adults, 797 and 680 individuals were eligible for CKD-EPI and MDRD analyses, respectively. CKD was defined as eGFR lower than 60 mL/min/1.73 m2. Multivariable Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CI) for all potential risk factors. RESULTS: The incidence rates (95% CI) of CKD per 1,000 person-years were 43.84 (39.49 to 48.66) and 55.80 (50.29 to 61.91) based on CKD-EPI and MDRD equations, respectively. Being older, a history of cardiovascular disease, and having lower levels of eGFR were significant risk factors in both equations. Moreover, in CKD-EPI, using glucose-lowering medications and hypertension, and in MDRD, female sex and fasting plasma glucose ≥10 mmol/L were also independent risk factors. Regarding the discrimination index, CKD-EPI equation showed a higher range of C-index for the predicted probability of incident CKD in the full-adjusted model, compared to MDRD equation (0.75 [0.72 to 0.77] vs. 0.69 [0.66 to 0.72]). CONCLUSION: We found an incidence rate of more than 4%/year for CKD development among our Iranian diabetic population. Compared to MDRD, it can be suggested that CKD-EPI equation can be a better choice to use for prediction models of incident CKD among the Iranian diabetic populations.

Adolescent metabolic syndrome and its components associations with incidence of type 2 diabetes in early adulthood: Tehran lipid and glucose study.

AIM: To investigate the association of youth metabolic syndrome (MetS) and its components, individually and in combination with early adulthood incident type 2 diabetes (T2DM). METHODS: A total of 2798 adolescents aged 11-19 years enrolled in the study. At baseline, MetS, its components including blood pressure (BP), waist circumference (WC), triglycerides (TGs), fasting plasma glucose, and low HDL-C, and different combinations of MetS components were defined. After a mean 11.3 years of follow-up, T2DM was determined. Multivariable Cox proportional hazard regression analysis adjusted for age, sex, family history of T2DM, and adult BMI was used for data analysis. The hazard ratio (HR) and 95% confidence interval (CI) were reported. RESULTS: During the follow-up, 44 incidents T2DM were developed. Among different individual components, only high WC [HR = 2.63, 95% CI (1.39-4.97)] and high TGs [HR = 1.82, 95% CI (1.00-3.34)] remained as significant predictors only in the age and sex adjusted model. Regarding combinations of MetS components, 'high TGs and high WC' [HR = 2.70, 95% CI (1.27-5.77)], 'high BP and high WC' [HR = 2.52, 95% CI (1.00-6.33)], 'high TGs and high BP' [HR = 2.27, 95% CI (1.02-5.05)] as well as MetS per se [HR = 2.82, 95% CI (1.41-5.64)] had a significant relationship with incident T2DM in the multivariable adjusted model. Among different confounders, being female and having family history of T2DM were consistently associated with higher risk of T2DM, in different combinations of MetS components. CONCLUSIONS: Adolescence MetS and some combinations of MetS components predicted early adulthood T2DM. Thus, adolescents, particularly female ones, with combinations of MetS components as well as those with family history of T2DM could be targeted for lifestyle intervention.

Sex-specific prevalence of coronary heart disease among Tehranian adult population across different glycemic status: Tehran lipid and glucose study, 2008-2011.

BACKGROUND: Coronary heart disease (CHD) is one of the leading causes of death. Alarmingly Iranian populations had a high rank of CHD worldwide. The current study aimed to assess the prevalence of CHD across different glycemic categories. METHODS: This study was conducted on 7718 Tehranian participants (Men = 3427) aged ≥30 years from 2008 to 2011. They were categorized based on glycemic status. The prevalence of CHD was calculated in each group separately. CHD was defined as hospital records adjudicated by an outcome committee. The association of different glycemic categories with CHD was calculated using multivariate logistic regression, compared with normal fasting glucose /normal glucose tolerance (NFG/NGT) group as reference. RESULTS: The age-standardized prevalence of isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT), both impaired fasting glucose and impaired glucose tolerance (IFG/IGT), newly diagnosed diabetes mellitus (NDM), and known diabetes mellitus (KDM) were 14.30% [95% confidence interval (CI): 13.50-15.09], 4.81% [4.32-5.29], 5.19% [4.71-5.67], 5.79% [5.29-6.28] and 7.72% [7.17-8.27], respectively. Among a total of 750 individuals diagnosed as cases of CHD (398 in men), 117 (15.6%), 453 (60.4%), and 317 (42.3%) individuals had a history of myocardial infarction (MI), cardiac procedure, and unstable angina, respectively. The age-standardized prevalence of CHD for the Tehranian population was 7.71% [7.18-8.24] in the total population, 8.62 [7.81-9.44] in men and 7.19 [6.46-7.93] in women. Moreover, among diabetic participants, the age-standardized prevalence of CHD was 13.10 [9.83-16.38] in men and 10.67 [8.90-12.44] in women, significantly higher than corresponding values for NFG/NGT and prediabetic groups. Across six levels of glycemic status, CHD was associated with IFG/IGT [odds ratio (OR) and 95% CI: 1.38 (1.01-1.89)], NDM [1.83 (1.40-2.41)], and KDM [2.83 (2.26-3.55)] groups, in the age- and sex-adjusted model. Furthermore, in the full-adjusted model, only NDM and KDM status remained to be associated with the presence of CHD by ORs of 1.40 (1.06-1.86) for NDM and 1.91 (1.51-2.43) for KDM. CONCLUSION: The high prevalence of CHD, especially among diabetic populations, necessitates the urgent implementation of behavioral interventions in the Tehranian population, according to evidence-based guidelines for the clinical management of diabetic patients.

The impact of triglyceride-glucose index on incident cardiovascular events during 16 years of follow-up: Tehran Lipid and Glucose Study.

BACKGROUND: To investigate whether the Triglyceride-Glucose index (TyG-index) is associated with increased risk of cardiovascular diseases (CVD)/coronary heart disease (CHD). METHODS: A total of 7521 Iranians aged ≥ 30 years (male = 3367) were included in the study. Multivariate Cox regression analyses (adjusted for age, gender, waist circumference, body mass index, educational level, smoking status, physical activity, family history of CVD, type 2 diabetes, hypertension, low and high density lipoprotein cholesterol, and lipid lowering drugs) were used to assess the risk of incident CVD/CHD across quintiles and for 1-standard deviation (SD) increase in the TyG-index. The cut off point for TyG-index was assessed by the minimum value of [Formula: see text]. We also examined the added value of the TyG-index in addition to the Framingham risk score when predicting CVD. RESULTS: During follow-up, 1084 cases of CVD (male = 634) were recorded. We found a significant trend of TyG-index for incident CVD/CHD in multivariate analysis (both Ps for tend ≤ 0.002). Moreover, a 1-SD increase in TyG-index was associated with significant risk of CVD/CHD in multivariate analysis [1.16 (1.07-1.25) and 1.19 (1.10-1.29), respectively]. The cut-off value of TyG-index for incident CVD was 9.03 (59.2% sensitivity and 63.2% specificity); the corresponding value of TyG-index for incident CHD was 9.03 (60.0% sensitivity and 62.8% specificity), respectively. Although no interaction was found between gender and TyG-index for CVD/CHD in multivariate analysis (both Ps for interaction > 0.085), the significant trend of TyG-index was observed only among females for incident CVD (P = 0.035). A significant interaction was found between age groups (i.e. ≥ 60 vs < 60 years) and TyG-index for CVD outcomes in the multivariate model (P-value for interaction = 0.046). Accordingly, a significant association between the TyG-index and outcomes was found only among the younger age group. Among the population aged < 60 the addition of TyG-index to the Framingham risk score (FRS) did not show improvement in the predictive ability of the FRS, using integrated discrimination improvement. CONCLUSION: The TyG-index is significantly associated with increased risk of CVD/CHD incidence; this issue was more prominent among the younger population. However, adding TyG-index to FRS does not provide better risk prediction for CVD.

Change in glucose intolerance status and risk of incident cardiovascular disease: Tehran Lipid and Glucose Study.

BACKGROUND: To assess the impact of changes in different glucose tolerance states on risk of incident cardiovascular disease (CVD)/coronary heart disease (CHD). METHODS: A total of 4094 Iranians (43.9% men) aged ≥ 30 years, without diabetes and CVD at enrolment were included. The following categories were defined both at baseline visit and 3 years later (second visit): normal fasting glucose (NFG), normal glucose tolerance (NGT), NFG and NGT (NFG/NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and IFG and/or IGT (IFG/IGT). Changes in the categories, i.e. regression to normoglycemia, remaining in previous status and progression to diabetes were assessed. We used Cox's proportional hazard models adjusted for traditional risk factors and their changes, to estimate the hazard ratio (HR) with 95% confidence interval (CI) of different changing categories for incident CVD/CHD. RESULTS: During a median follow-up of 12.42 years, 428 subjects (men = 265) experienced CVD. Considering persistent NFG/NGT as reference, participants who shifted from NFG/NGT to IFG/IGT showed a lower hazard of CVD in the fully adjusted model, HR 0.72 [95% CI 0.52-0.996, P = 0.048]. Moreover, subjects who shifted from IFG, IGT and IFG/IGT to diabetes had an increased risk of CVD/CHD. The risk however, was only statistically significant for those with IFG/IGT, 1.61 [(1.03-2.51), P = 0.04] for CVD and 1.75 [(1.10-2.78), P = 0.02] for CHD; considering IFG/IGT at both visits as reference. Furthermore, those who regressed from IFG/IGT to normoglycemia were at the same risk as those remained in IFG/IGT state, 1.12 [(0.79-1.60), P = 0.52] for CVD and 1.04 [(0.70-1.53), P = 0.85] for CHD. Among a subgroup of population with insulin data (n = 803) those with insulin resistance (IR) that converted to diabetes showed a higher risk for CVD, 3.68 [(1.49-9.06), P = 0.01] and CHD, 2.76 [(1.00-7.60), P = 0.05] events in the fully adjusted model. CONCLUSIONS: Among participants with IFG, IGT or IFG/IGT at baseline, only those who developed diabetes had a higher risk of developing CVD/CHD. Persistent IFG/IGT was not associated with higher risk, compared with those reverted to normoglycemia. Moreover, subjects who converted from NFG/NGT to incident IFG/IGT showed a signal for lower risk of CVD/CHD.

Impact of 3-year changes in fasting insulin and insulin resistance indices on incident hypertension: Tehran lipid and glucose study.

BACKGROUND: To examine the association between changes in fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and insulin-glucose ratio (IGR) levels, over approximately 3 years with incident hypertension. METHODS: A total of 2814 Iranian participants (1123 men) without hypertension and known diabetes at baseline and the first examination were followed for a median of 6.32 years. The associations between quartiles of changes in fasting insulin and IR indices with incident hypertension were assessed using multivariate Cox proportional hazard regression analyses with first quartile as reference. The models were adjusted for baseline values of insulin or each IR index, and age, sex, smoking, physical activity, educational levels, marital status, history of cardiovascular diseases, baseline levels of systolic and diastolic blood pressures, estimated glomerular filtration rate, triglycerides, total cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose (only for insulin change) and both body mass index (BMI) per se, and its change. Akaike's information criteria (AIC) was applied as indicator for goodness of fit of each predictive model. The discrimination ability of models was calculated using the Harrell's C statistic. RESULTS: During the study, 594 incident cases of hypertension (253 men) were identified. The 4th quartile of changes in insulin, HOMA-IR, and IGR showed hazard ratios (95% confidence interval) of 1.31 (1.01-1.69), 1.18 (0.92-1.52), and 1.53 (1.18-1.98) for hypertension, respectively, in fully-adjusted models. Changes in fasting insulin levels and IR indices showed significant increasing trends for incident hypertension, moving from 1st to 4th quartiles (all P-values < 0.05). Focusing on model fitness, no superiority was found between changes in fasting insulin, HOMA-IR, and IGR to predict incident hypertension. The discriminatory powers of changes in fasting insulin and IR indices as assessed by C index were similar (i.e. about 80%). CONCLUSION: Changes in fasting insulin and IR indices were significantly associated with developing hypertension among normotensive population even after considering BMI changes.