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.

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.

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.

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.

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

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

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.

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.

Predictors of decline in kidney function in the general population: a decade of follow-up from the Tehran Lipid and Glucose Study.

BACKGROUND AND AIMS: We aimed to assess the potential socio-demographic, clinical, and lifestyle-related risk factors for kidney function decline (KFD), defined as ≥30% estimated glomerular filtration rate (eGFR) decline, in an Iranian cohort study. METHODS: 7190 participants (4049 women) aged 20-90 years with 2-5 eGFR data from examinations (2001-2005 to 2015-2018) were included. Cox proportional hazard models were used to examine the association between potential risk factors and eGFR decline. RESULTS: During 11.5 years of follow-up, 1471 (889 women) participants had incident KFD with a crude incidence rate of 192.1 (182.6-202.2) per 10,000 person-year. Among the total population, older age, female gender, prehypertension, hypertension, diabetes, widowed/divorced states, higher triglycerides (TG), prevalent cardiovascular diseases (CVD), and higher baseline eGFR were significantly associated with higher, while moderate physical activity and a positive family history of diabetes were associated with lower risk of KFD (all p values <.05). Prevalent CVD in women but not men, diabetes, and hypertension among postmenopausal than premenopausal women were significant risk factors of KFD. According to the presence of chronic kidney disease (CKD) at baseline, higher eGFR decreased the risk of KFD in patients with CKD and increased KFD risk in those without CKD (all p for interactions <.05). CONCLUSION: KFD is associated with multiple modifiable risk factors among the Iranian urban population that is affected by gender, menopausal status, and initial kidney function. Interventions targeting these factors might potentially help reduce the burden of KFD.Key messages:Menopausal status may influence the relationship between cardiometabolic risk factors and KFD;The impact of higher baseline eGFR on the risk of KFD differed between subjects with preserved kidney function and CKD patients.The interaction between gender, menopausal status, and baseline kidney function with different risk factors on KFD may help to make renal risk prediction scores to identify those in the general population at risk who may benefit from early prevention.

The association between fasting plasma glucose variability and incident eGFR decline: evidence from two cohort studies.

BACKGROUND: Glycemic variability (GV) is developing as a marker of glycemic control, which can be utilized as a promising predictor of complications. To determine whether long-term GV is associated with incident eGFR decline in two cohorts of Tehran Lipid and Glucose Study (TLGS) and Multi-Ethnic Study of Atherosclerosis (MESA) during a median follow-up of 12.2 years. METHODS: Study participants included 4422 Iranian adults (including 528 patients with T2D) aged ≥ 20 years from TLGS and 4290 American adults (including 521 patients with T2D) aged ≥ 45 years from MESA. The Multivariate Cox proportional hazard models were used to assess the risk of incident eGFR decline for each of the fasting plasma glucose (FPG) variability measures including standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and variability independent of the mean (VIM) both as continuous and categorical variables. The time of start for eGFR decline and FPG variability assessment was the same, but the event cases were excluded during the exposure period. RESULTS: In TLGS participants without T2D, for each unit change in FPG variability measures, the hazards (HRs) and 95% confidence intervals (CI) for eGFR decline ≥ 40% of SD, CV, and VIM were 1.07(1.01-1.13), 1.06(1.01-1.11), and 1.07(1.01-1.13), respectively. Moreover, the third tertile of FPG-SD and FPG-VIM parameters was significantly associated with a 60 and 69% higher risk for eGFR decline ≥ 40%, respectively. In MESA participants with T2D, each unit change in FPG variability measures was significantly associated with a higher risk for eGFR decline ≥ 40%.Regarding eGFR decline ≥ 30% as the outcome, in the TLGS, regardless of diabetes status, no association was shown between FPG variability measures and risk of eGFR decline in any of the models; however, in the MESA the results were in line with those of GFR decline ≥ 40%.Using pooled data from the two cohorts we found that generally FPG variability were associated with higher risk of eGFR decline ≥ 40% only among non-T2D individuals. CONCLUSIONS: Higher FPG variability was associated with an increased risk of eGFR decline in the diabetic American population; however, this unfavorable impact was found only among the non-diabetic Iranian population.

The Association between COVID-19 and Reactive Arthritis: A Systematic Review of Case Reports and Case Series.

INTRODUCTION: Reactive arthritis (ReA) is a joint inflammation that follows an infection at a distant site, often in the gastrointestinal or urogenital tract. Since the emergence of COVID-19 in January 2020, several case reports have suggested a relation between reactive arthritis and severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), due to the novelty of the disease, most findings were reported in the form of case reports or case series, and a comprehensive overview is still lacking. METHODS: We searched PubMed/Medline and Embase to identify studies addressing the association between ReA and COVID-19. The following terms were used: ("Reactive Arthritis" OR "Post-Infectious Arthritis" OR "Post Infectious Arthritis") AND ("COVID-19" OR "SARS-CoV-2" OR "2019-nCoV"). RESULTS: A total number of 35 reports published up to February 16th, 2022, were included in this study. A wide range of ages was affected (mean 41.0, min 4 max 78), with a higher prevalence of males (61.0%) from 16 countries. The number and location of the affected joints were different in included patients, with a higher prevalence of polyarthritis in 41.5% of all cases. Cutaneous manifestations and visual impairments were found as the most common associated symptoms. Most patients (95.1%) recovered, with a mean recovery time of 24 days. Moreover, arthritis induced by COVID-19 seems to relieve faster than ReA, followed by other infections. CONCLUSION: ReA can be a possible sequel of COVID-19 infection. Since musculoskeletal pain is a frequent symptom of COVID-19, ReA with rapid onset can easily be misdiagnosed. Therefore, clinicians should consider ReA a vital differential diagnosis in patients with post-COVID-19 joint swelling. Additional studies are required for further analysis and to corroborate these findings.

Changes in Fasting plasma glucose status and risk of mortality events in individuals without diabetes over two decades of Follow-up: a pooled cohort analysis.

BACKGROUND: We aimed to assess the gender-specific impact of 3-year changes in fasting plasma glucose (FPG) status on the risk of all-cause, cardiovascular (CV), and cancer mortality in individuals without type 2 diabetes (T2DM) during an 18-year follow-up. METHODS: The study population included 14,378 participants aged 30-60 years (8272 women) from three population-based cohort studies, including Atherosclerosis Risk in Communities, Multi-Ethnic Study of Atherosclerosis, and Tehran Lipid and Glucose Study. Subjects were classified into six categories based on the approximately three-year changes in FPG status: (1) normal FPG (NFG) to NFG (reference category); (2) NFG to impaired fasting glucose (IFG) (i.e., 126 > FPG ≥ 100 mg/dl); (3) NFG to T2DM; (4) IFG to NFG; (5) IFG to IFG; (6) IFG to T2DM. Multivariable stratified Cox regression, adjusting for age, body mass index (BMI), BMI-Change, smoking status, hypertension, and hypercholesterolemia was used to estimate hazard ratios (HRs (95% CI)) for all-cause and cause-specific mortality events. Women-to-men ratios of HRs (RHRs) for each category were also estimated. RESULTS: During follow-up, 2,362 all-cause mortality events were recorded. Among women, all categories of FPG change, excluding IFG-NFG (HR, 95%CI 1.24 (0.98-1.57), p = 0.07), were associated with a higher risk of all-cause mortality compared to the NFG-NFG category. Moreover, women in IFG-T2DM group were at increased risk for CV mortality (2.21 (1.42-3.44)). We also found that women in NFG-IFG (1.52 (1.20-1.91)), NFG-T2DM (2.90 (1.52-5.51)), and IFG-IFG (1.30 (1.02-1.66)) categories had a higher risk for cancer mortality. However, among men, a higher risk of all-cause mortality was found for only two groups of NFG-T2DM (1.78 (1.15-2.74)) and IFG-T2DM (1.34 (1.04-1.72)). Women with IFG-IFG had a 24% higher risk for all-cause mortality events than their men counterparts (RHR; 1.24 (1.01-1.54)). After further adjustment for physical activity, results were in line with the main findings, excluding T2DM up to six years after the measurement period and early mortality events. CONCLUSION: In women, the IFG status, whether as incident, persistent, or converted to T2DM, had a higher risk for mortality events; however, among men, only conversion to T2DM conferred an excess risk of all-cause mortality.

The clinical value of metabolic syndrome and its components with respect to sudden cardiac death using different definitions: Two decades of follow-up from the Tehran Lipid and Glucose Study.

BACKGROUND: To evaluate the impact of different definitions of metabolic syndrome (MetS) and their components on the risk of sudden cardiac death (SCD) among the Iranian population according to the World Health Organization (WHO), International Diabetes Federation (IDF), Adult Treatment Panel III (ATP III), and Joint Interim Statement (JIS) criteria. METHODS: The study population included a total of 5,079 participants (2,785 women) aged ≥ 40 years, free of cardiovascular disease (CVD) at baseline. Participants were followed for incident SCD annually up to 20 March 2018. Multivariable Cox proportional hazards regression models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of MetS and its components for incident SCD. RESULTS: The prevalence of MetS ranged from 27.16% to 50.81%, depending on the criteria used. Over a median of 17.9 years of follow-up, 182 SCD events occurred. The WHO, IDF, and JIS definitions were strong predictors of SCD with multivariable-adjusted HRs (95% CI) of 1.68 (1.20-2.35), 1.51 (1.12-2.03), and 1.47 (1.08-1.98), respectively; these associations significantly attenuated after further adjustment for MetS components. MetS by the ATP III definition was not associated with the risk of SCD after controlling for antihypertensive, glucose-lowering, and lipid-lowering medication use. Among the components of MetS, high blood pressure (WHO definition), high waist circumference (using the national cutoff of ≥ 95 cm), and high glucose component by the JIS/IDF definitions remained independent predictors of SCD with HRs of 1.79 (1.29-2.48), 1.46 (1.07-2.00), and 1.52 (1.12-2.05), respectively. CONCLUSIONS: The constellation of MetS, except for when defined with ATP III definition, is a marker for identifying individuals at higher risk for SCD; however, not independent of its components. Among MetS components, abdominal obesity using the population-specific cutoff point, high glucose component (JIS/IDF definitions), and high blood pressure (WHO definition) were independent predictors of SCD.

Mean versus variability of lipid measurements over 6 years and incident cardiovascular events: More than a decade follow-up.

Background: Lipid variability (LV) has emerged as a contributor to the incidence of cardiovascular diseases (CVD), even after considering the effect of mean lipid levels. However, these associations have not been examined among people in the Middle East and North Africa (MENA) region. We aimed to investigate the association of 6-year mean lipid levels versus lipid variability with the risk of CVD among an Iranian population. Methods: A total of 3,700 Iranian adults aged ≥ 30 years, with 3 lipid profile measurements, were followed up for incident CVD until March 2018. Lipid variability was measured as standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and variability independent of mean (VIM). The effects of mean lipid levels and LV on CVD risk were assessed using multivariate Cox proportional hazard models. Results: During a median 14.5-year follow-up, 349 cases of CVD were recorded. Each 1-SD increase in the mean levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C), and non-HDL-C increased the risk of CVD by about 26-29%; for HDL-C, the risk was significantly lower by 12% (all p-values < 0.05); these associations resisted after adjustment for their different LV indices. Considering LV, each 1-SD increment in SD and ARV variability indices for TC and TC/HDL-C increased the risk of CVD by about 10%; however, these associations reached null after further adjustment for their mean values. The effect of TC/HDL-C variability (measured as SD) and mean lipid levels, except for LDL-C, on CVD risk was generally more pronounced in the non-elderly population. Conclusion: Six-year mean lipid levels were associated with an increased future risk of incident CVD, whereas LV were not. Our findings highlight the importance of achieving normal lipid levels over time, but not necessarily consistent, for averting adverse clinical outcomes.

Differences in the impact of impaired glucose status on clinical outcomes in younger and older adults: Over a decade of follow-up in the Tehran lipid and glucose study.

Introduction: Studies found that the impact of dysglycemia on microvascular, macrovascular events and mortality outcomes were different between the younger vs. older population. We aimed to investigate the age-specific association of prediabetes with clinical outcomes including type 2 diabetes (T2DM), hypertension, chronic kidney disease (CKD), cardiovascular disease (CVD), and mortality. Materials and methods: A total of 5,970 Iranians (3,829 women) aged ≥30 years, without T2DM, were included. The age-specific (<60 and ≥60 years; minimum p-value for interaction = 0.001) multivariable-adjusted Cox regression was done to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of the impaired glucose status including impaired fasting glucose (IFG) vs. normal fasting glucose (NFG), impaired glucose tolerance (IGT) vs. normal glucose tolerance (NGT), and IFG&IGT vs. NFG/NGT with each outcome. Results: Among individuals aged ≥60 years, the prevalence of impaired glucose status (IFG, IGT, or both) was about 2 times higher compared to those aged <60. Age-specific association between prediabetes and incident hypertension was found for those aged <60 years; [HR (95% CI); IFG: 1.38 (1.16-1.65), IGT: 1.51 (1.26-1.81), and IFG&IGT: 1.62 (1.21-2.12)]. For CVD, in all impaired glycemic states, those aged <60 were at higher significant risk [IFG: 1.39 (1.09-1.77), IGT: 1.53 (1.19-1.97), and IFG&IGT: 1.60 (1.14-2.25)]. Stratified analyses showed similar associations for IFG and IGT with non-CV mortality 1.71 (1.04-2.80) and 2.12 (1.30-3.46), respectively, and for all-cause mortality among those aged <60 years [IFG: 1.63 (1.08-2.45) and IGT: 1.82 (1.20-2.76)]. In both age groups, all glycemic status groups were significantly associated with T2DM but not with CKD and CV mortality. Conclusions: The high prevalence of prediabetes particularly among the elderly population, limited resources, and the observed significant age differences in the impact of prediabetes states on different clinical outcomes calls for multicomponent intervention strategies by policy health makers, including lifestyle and possible pharmacological therapy, with the priority for the young Iranian population.

Autologous hematopoietic stem cell transplantation in neuromyelitis optica spectrum disorder: A systematic review and meta-analysis.

INTRODUCTION: Treatment options for neuromyelitis optica spectrum disorder (NMOSD) are corticosteroids, immunosuppressive drugs, emerging monoclonal antibodies, rituximab, eculizumab, satralizumab, and inebilizumab. Due to disabling and deadly nature of NMOSD, there is a great motivation among physicians for finding new treatment options. Recently, several studies have been conducted on the therapeutic effects of autologous hematopoietic stem cell transplantation (AHSCT) on NMOSD patients. METHODS: Several databases including PubMed, Scopus, Web of Science, and Google scholar were searched for studies on AHSCT in NMOSD patients. RESULTS: After screening titles and abstracts, and reviewing full texts, nine studies with 39 severe cases of NMOSD met the criteria of our study. The pooled standardized mean difference (SMD) for EDSS score before and after treatment was -0.81 (95 %CI:-1.07, -0.15; Q = 1.99, P = 0.58, I2 = 0 %). Also, the PFS and RFS were 69 % and 53 % respectively (PFS: 69 %, 95 %CI 42 %, 96 %; Q = 8.63, P = 0.01, I2 = 73.07 %; RFS: 53 %, 95 %CI 27 %, 79 %; Q = 12.33, P = 0.01, I2 = 71.87 %). Also, there were three cases with secondary autoimmune diseases including myasthenia gravis, hyperthyroidism, and thyroiditis. CONCLUSION: According to the present study, AHSCT could be an alternative therapy for NMOSD in severe cases instead of conventional immunotherapies. However, physicians should pay attention to its serious complications. The diversity of results from the published trials on the efficacy and safety of AHSCT calls for further investigations on determining the ideal AHSCT conditioning and the characteristics of patients.

Association of ideal cardiovascular health metrics and incident type 2 diabetes mellitus among an urban population of Iran: One decade follow up in the Tehran Lipid and Glucose Study.

AIMS/INTRODUCTION: To evaluate the association between ideal cardiovascular health metrics (ICVHM) and incident type 2 diabetes mellitus among Iranian men and women. MATERIALS AND METHODS: The study population included 7,488 Iranian adults aged ≥20 years (4,236 women) free from diabetes at baseline. The ICVHM was defined according to the American Heart Association's 2020 impact goals. The multivariable Cox proportional hazards regression analysis was used to calculate the hazard ratios (HRs) for ICVHM both as continuous and categorical variables. RESULTS: Over the median of 9.1 years of follow-up, we identified 922 new cases of type 2 diabetes mellitus (526 women). Body mass index <30 kg/m2 , untreated systolic/diastolic blood pressure <120/80 mmHg in both sexes, and physical activity ≥1,500 MET min/week (only among men) were significantly associated with a lower risk of type 2 diabetes mellitus. Each additional unit in the ICVHM was associated with a 21 and 15% lower risk of type 2 diabetes mellitus in men and women, respectively (P-values <0.05). Compared with participants having poor cardiovascular health, the HR for type 2 diabetes mellitus risk was 0.69 (95% confidence interval [CI] 0.56-0.85) and 0.35 (95% CI 0.21-0.59) for men with intermediate and ideal CVHM, respectively. The corresponding values for women were 0.79 (95% CI 0.65-0.97) and 0.30 (95% CI 0.15-0.60), respectively. In a subpopulation with nutritional data (n = 2,236), ideal and intermediate nutritional status was associated with 83 and 77% lower risk of type 2 diabetes mellitus only among women (P-values <0.05). CONCLUSION: We found a strong inverse association between having higher global ICVHM with incident type 2 diabetes mellitus; which is mainly attributable to normal blood pressure, normal body weight, and intensive physical activity (only for men).

Natural products in suppressing glioma progression: A focus on the role of microRNAs.

Glioma is one of the most common malignancies of the central nervous system. Due to inadequate response to the current treatments available, glioma has been at the center of recent cancer studies searching for novel treatment strategies. This has prompted an intensive search using linkage studies and preliminary evidence to gain efficient insight into the mechanisms involved in the alleviation of the pathogenesis of glioma mediated by miRNAs, a group of noncoding RNAs that affect gene expression posttranscriptionally. Dysregulated expression of miRNAs can exacerbate the malignant features of tumor cells in glioma and other cancers. Natural products can exert anticancer effects on glioma cells by stimulating the expression levels of tumor suppressor miRNAs and repressing the expression levels of oncogenic miRNAs. In this review, we aimed to collect and analyze the literature addressing the roles of natural products in the treatment of glioma, with an emphasis on their involvement in the regulation of miRNAs.

Artificial intelligence in the diagnosis of multiple sclerosis: A systematic review.

BACKGROUND: In recent years Artificial intelligence (AI) techniques are rapidly evolving into clinical practices such as diagnosis and prognosis processes, assess treatment effectiveness, and monitoring of diseases. The previous studies showed interesting results regarding the diagnostic efficiency of AI methods in differentiating Multiple sclerosis (MS) patients from healthy controls or other demyelinating diseases. There is a great lack of a comprehensive systematic review study on the role of AI in the diagnosis of MS. We aimed to perform a systematic review to document the performance of AI in MS diagnosis. METHODS: A systematic search was performed using four databases including PubMed, Scopus, Web of Science, and IEEE on August 2021. All original studies which focused on deep learning or AI to analyze any modalities with the purpose of diagnosing MS were included in our study. RESULTS: Finally, 38 studies were included in our systematic review after the abstract and full-text screening. A total of 5433 individuals were included, including 2924 cases of MS and 2509 healthy controls. Sensitivity and specificity were reported in 29 studies which ranged from 76.92 to 100 for sensitivity and 74 to 100 for specificity. Furthermore, 34 studies reported accuracy ranged 81 to 100. Among included studies, Magnetic Resonance Imaging (MRI) (20 studies), OCT (six studies), serum and cerebrospinal fluid markers (six studies), movement function (three studies), and other modalities such as breathing and evoked potential was used for detecting MS via AI. CONCLUSION: In conclusion, diagnosis of MS based on new markers and AI is a growing field of research with MRI images, followed by images obtained from OCT, serum and CSF biomarkers, and motor associated markers. All of these results show that with advances made in AI, the way we monitor and diagnose our MS patients can change drastically.

Targeting miRNAs with anesthetics in cancer: Current understanding and future perspectives.

Anesthetics are extensively used during cancer surgeries. The progression of cancer can be influenced by perioperative events such as exposure to general or local anesthesia. However, whether they inhibit cancer or act as a causative factor for metastasis and exert deleterious effects on cancer growth differs based on the type of cancer and the therapy administration. Recent experimental data suggested that many of the most commonly used anesthetics in surgical oncology, whether general or local agents, can alter gene expression and cause epigenetic changes via modulating miRNAs. miRNAs are single-stranded non-coding RNAs that regulate gene expression at various levels, and their dysregulation contributes to the pathogenesis of cancers. However, anesthetics via regulating miRNAs can concurrently target several effectors of cellular signaling pathways involved in cell differentiation, proliferation, and viability. This review summarized the current research about the effects of different anesthetics in regulating cancer, with a particular emphasis on the role of miRNAs. A significant number of studies conducted in this area of research illuminate the effects of anesthetics on the regulation of miRNA expression; therefore, we hope that a thorough understanding of the underlying mechanisms involved in the regulation of miRNA in the context of anesthesia-induced cancer regulation could help to define optimal anesthetic regimens and provide better perspectives for further studies.