Effectiveness of polypill for primary and secondary prevention of cardiovascular disease: a pragmatic cluster-randomised controlled trial (PolyPars).

BACKGROUND: We aimed to investigate the effectiveness of fixed-dose combination therapy (polypill) for primary and secondary prevention of major cardiovascular diseases in a typical rural setting. METHODS: The PolyPars Study is a two-arm pragmatic cluster-randomised trial nested within the PARS cohort study, including all residents aged over 50 years in the entire district in southern Iran. The 91 villages underwent random allocation into two arms: the control arm, encompassing 45 clusters, was subjected to non-pharmacological intervention (educational training on healthy lifestyle), whereas the intervention arm, comprising 46 clusters, received the non-pharmacological interventions in conjunction with a once-daily polypill tablet. This tablet comprised two antihypertensive agents, a statin and aspirin. The primary outcome was the first occurrence of major cardiovascular events defined as a composite of hospitalisation for acute coronary syndrome (non-fatal myocardial infarction and unstable angina), fatal myocardial infarction, non-fatal and fatal stroke, sudden death and heart failure. The Cox regression model, with shared frailty, was used to account for clustering effect. RESULTS: During December 2015-December 2016, a total of 4415 participants aged 50-75 years were recruited (2200 participants in the intervention arm and 2215 participants in the control arm). The overall median of follow-up duration was 4.6 years (interquartile interval 4.4-4.9). The achieved adherence rate to polypill in intervention arm was 86%. In the control group, 176 (8.0%) of 2215 participants developed primary outcome, compared with 88 (4.0%) of 2200 participants in the polypill group. We found substantial reduction in risk of primary outcome both in relative and absolute scales (HR 0.50, 95% CI 0.38 to 0.65; absolute risk reduction 4.0%, 95% CI 2.5% to 5.3%). No difference in serious adverse events was observed between the two groups. CONCLUSIONS: The fixed-dose combination therapy using polypill can safely halve the risk of major cardiovascular diseases at the population level. TRIAL REGISTRATION NUMBER: NCT03459560.

Fixed-Dose Combination Therapy for the Prevention of Cardiovascular Diseases in CKD: An Individual Participant Data Meta-Analysis.

BACKGROUND: Fixed-dose combination treatments reduce cardiovascular disease in primary prevention. We aim to explore whether those benefits differ in the presence of CKD. METHODS: We conducted an individual participant data meta-analysis in 18,162 participants on the efficacy and safety of treatment for the primary prevention of cardiovascular disease. Combination therapies consisted of at least two BP-lowering drugs and a statin, with or without aspirin versus placebo or minimal care. Here, we examine the differential effect of fixed-dose combination treatment on the risk of developing cardiovascular disease in participants with a low eGFR (<60 ml/min per 1.73 m 2 ; Chronic Kidney Disease Epidemiology Collaboration formula) compared with a normal eGFR (≥60 ml/min per 1.73 m 2 ). The primary composite outcome was time to first occurrence of a combination of cardiovascular death, myocardial infarction, stroke, or arterial revascularization. RESULTS: At baseline, the mean level of eGFR was 76 ml/min per 1.73 m 2 (SD 17). In total, 3315 (18%) participants had low eGFR at baseline. During a median follow-up of 5 years, among participants with normal eGFR, the primary outcome occurred in 232 (3%) participants in the treatment group compared with 339 (5%) in the control group (hazard ratio, 0.68; 95% confidence interval, 0.57 to 0.81; P < 0.001). In participants with low eGFR, the primary outcome occurred in 64 (4%) participants in the treatment group compared with 130 (8%) in the control group (hazard ratio, 0.49; 95% confidence interval, 0.36 to 0.66; P < 0.001; P for interaction 0.047). The relative risk reduction among participants with low eGFR was larger for combination strategies, including aspirin compared with treatments without aspirin. Apart from dizziness, other side effects did not differ between treatment and control groups, regardless of the stage of their kidney function. CONCLUSIONS: A fixed-dose combination treatment strategy is effective and safe at preventing cardiovascular disease, irrespective of eGFR, but relative and absolute risk reductions are larger in individuals with low eGFR. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_11_08_CJN0000000000000251.mp3.

Association of indoor use of pesticides with CKD of unknown origin.

INTRODUCTION: Chronic kidney disease (CKD) is a growing global health problem. Recently, an epidemic of CKD of unknown origin (CKDu), a form of CKD seen mostly in agricultural communities, has been emerged. One of the proposed causes of CKDu is pesticide use in farmers. On the other hand, the research on relation between indoor use of pesticides and CKDu is little. In this study, we aimed to investigate the association between indoor use of pesticide as well as the exposure time with CKDu. This study was done as part of the population-based cohort of Prospective Epidemiological Research Studies in Iran. We used the baseline data of the Zahedan Adult Cohort Study. All subjects with diabetes mellitus and/or hypertension, estimated glomerular filtration rate (eGFR) between 60-89 ml/min/1.73 m2, and unavailable creatinine measurement were excluded. Subjects with an eGFR of less than 60 ml/min/1.73 m2 were defined as having CKDu, and their data were compared with those with an eGFR of more than 90 ml/min/1.73 m2. Data regarding indoor pesticide use and duration of exposure were obtained through a questionnaire. After applying the exclusion criteria, 1079 subjects remained in the study. Female sex, single marital status, low physical activity, triglyceride (TG) levels of more than 150 mg/dl, body mass index (BMI) of more than 25 kg/m2, non-smokers, indoor pesticide use, and high pesticide exposure time were associated with CKDu. The effects of age, female sex, TG levels more than 150 mg/dl, pesticide use (OR 1.36; 95% CI 1.01-1.84), and high exposure time (third tertile of exposure time) compared to non-users (OR 1.64; 95% CI 1.07-2.51) remained significant in multivariable analysis. CONCLUSION: We found a positive association between pesticide use, as well as longer exposure time to pesticides, and impaired kidney function in cases without diabetes mellitus and hypertension. Further longitudinal studies should be carried out to confirm these findings.

The levels and trends of diabetes prevalence at national and sub-national levels in Iran (1990 - 2016).

Background: The increasing trends in Diabetes prevalence and its attributed burden emphasized as an important issue that needs serious and urgent attention, all over the word. We estimated the mean Fasting Plasma Glucose (FPG) and the prevalence of Diabetes in aged 25 years or older Iranian adults, by sex, age, province, and year through the time period of 1990 to 2016. Methods: In order to access the most comprehensive relevant data at the same time the systematic data searched added to the data of 5 national surveys and 7 sub-national population based investigations. Two round of modeling, including the Age-Spatio-Temporal and Gaussian Process Regression were used for estimation of mean FPG trend and uncertainties. To estimate Diabetes estimations in target groups, a crosswalk model was applies to the FPG estimates. The model reiterated separately for women and men. All of estimations standardized based on the Iran national census population of 2016 by year, age groups and sexes at national and sub-national levels. Results: In 2016, the number of the diabetic population was 4.43 (3.93-4.99) million (2.38 million women). Between 1990 and 2016, the age-standardized mean of FPG increased from 84.69 mg/dl (79.8-89.8) to 100.5 mg/dl (97.9-103.3) in women and from 82.7 mg/dl (78.3-87.5) to 98.8 mg/dl (96.2-101.4) in men. Simultaneously, with considerable difference, the Diabetes prevalence, has increased from 6.1% (4.7-7.8) to 9.8% (8.7-11.1) in women and from 5.0% 18 (3.8-6.3) to 8.1% (7.2-9.2) in men (75% attributed to population growth). Considering the geographical patterns, the greatest increment in the prevalence of Diabetes detected in the northwestern and the central provinces. Conclusion: Significant increasing trends of Diabetes led to alarming threat, which can make the strategies and goals of our prevention programs out of control. We should plan for more effective communicative interventions for prevention and management of Diabetes, to be designed, implemented and monitored based on the updated scientific evidence. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01197-2.

Diet Quality and Subsequent Incidence of Upper Gastrointestinal Cancers: Results from the Golestan Cohort Study.

BACKGROUND: Recent evidence suggests overall diet quality, as assessed by dietary scores, may play a role in the development of upper gastrointestinal (UGI) cancers. However, the existing dietary scores are derived from high-income countries with different dietary habits than regions with the highest burden of UGI cancers, where limited data is available. This study aimed to investigate the association between overall diet quality and risk of esophageal and stomach cancers in a high-risk region for UGI cancers. METHODS: We recruited 50045 individuals aged 40-75 between 2004-2008 from northeastern Iran and followed them annually through July 2020. Data on demographics, diet, and various exposures were collected using validated questionnaires. Diet quality was assessed by calculating the Healthy Eating Index (HEI), Alternative Healthy Eating Index (AHEI), Alternative Mediterranean Diet (AMED), Dietary Approaches to Stop Hypertension (DASH), and World Cancer Research Fund-American Institute for Cancer Research (WCRF-AICR) scores. RESULTS: During an average 12 years of follow-up, 359 participants developed esophageal cancer and 358 developed stomach cancer. After adjustments, each standard deviation increase in baseline dietary scores was associated with up to 12% reduction in esophageal cancer risk and up to 17% reduction in stomach cancer risk. Esophageal cancer showed stronger inverse associations with adherence to AMED (HRQ4-vs-Q1=0.69 (0.49-0.98), P-trend=0.038). Stomach cancer showed stronger inverse correlation with WCRF-AICR (HRQ4-vs-Q1=0.58 (0.41-0.83), P-trend=0.004), and DASH (HRC4-vs-C1=0.72 (0.54-0.96), P-trend=0.041). These associations were comparable across different population subgroups. We did not observe significant associations between HEI and AHEI scores and UGI cancers in this population. CONCLUSION: Despite the differences in consuming individual food groups, adherence to the available dietary recommendations (derived from high-income countries) was associated with lower risk for subsequent esophageal and gastric cancers in this high-risk population. Educating the public to have a healthy eating pattern might be an effective strategy towards prevention of UGI cancers in high-risk regions.

Socioeconomic inequalities in prevalence, awareness, treatment and control of hypertension: evidence from the PERSIAN cohort study.

BACKGROUND: Elevated blood pressure is associated with cardiovascular disease, stroke and chronic kidney disease. In this study, we examined the socioeconomic inequality and its related factors in prevalence, Awareness, Treatment and Control (ATC) of hypertension (HTN) in Iran. METHOD: The study used data from the recruitment phase of The Prospective Epidemiological Research Studies in IrAN (PERSIAN). A sample of 162,842 adults aged > = 35 years was analyzed. HTN was defined according to the Joint National Committee)JNC-7(. socioeconomic inequality was measured using concentration index (Cn) and curve. RESULTS: The mean age of participants was 49.38(SD = ± 9.14) years and 44.74% of the them were men. The prevalence of HTN in the total population was 22.3%(95% CI: 20.6%; 24.1%), and 18.8%(95% CI: 16.8%; 20.9%) and 25.2%(95% CI: 24.2%; 27.7%) in men and women, respectively. The percentage of awareness treatment and control among individuals with HTN were 77.5%(95% CI: 73.3%; 81.8%), 82.2%(95% CI: 70.2%; 81.6%) and 75.9%(95% CI: 70.2%; 81.6%), respectively. The Cn for prevalence of HTN was -0.084. Two factors, age (58.46%) and wealth (32.40%), contributed most to the socioeconomic inequality in the prevalence of HTN. CONCLUSION: The prevalence of HTN was higher among low-SES individuals, who also showed higher levels of awareness. However, treatment and control of HTN were more concentrated among those who had higher levels of SES, indicating that people at a higher risk of adverse event related to HTN (the low SES individuals) are not benefiting from the advantage of treatment and control of HTN. Such a gap between diagnosis (prevalence) and control (treatment and control) of HTN needs to be addressed by public health policymakers.

The association of dietary intake and plasma fatty acid panel in pancreatic cancer patients: Results from Golestan cohort study.

BACKGROUND & AIMS: High mortality rate of pancreatic cancer (PC) as one of the most common cancers worldwide made it a center of attention for recent researches on its pathology, etiology, screening and early diagnosis. In previous researches, association of dietary intake and plasma levels of fatty acids with risk of pancreatic cancer was investigated. In this study we aimed to evaluate the correlation between dietary and plasma fatty acids in case and control groups. METHODS: From 50,045 adults between 40-75 years old participated in Golestan cohort study, fifty incident cases of PC were diagnosed and 150 controls matched by age, sex and residence place were randomly selected. Dietary intakes and plasma levels of fatty acids was evaluated by validated food-frequency questionnaire (FFQ) and Gas Chromatography - Flame Ionization Detector (GC-FID), respectively. Then, Spearman's correlation was used to measure the correlation between dietary and plasma levels of fatty acids in case and control groups. RESULTS: Among all the fatty acids, there was a significant association between plasma and dietary intake of a few fatty acids including trans fatty acids (TFA), polyunsaturated fatty acids (PUFA), 22:6n-3 and 14:0 only in control group. Only total PUFA intake modified plasma level of some fatty acids in case group. There was no difference between association of desaturase enzymes and fatty acids in case and controls. CONCLUSIONS: Since, plasma levels of fatty acids might be influenced by recent diet, we did not find any specific differences between the associations of plasma levels of fatty acids with dietary intake of fats in case and control groups.

Spatial environmental factors predict cardiovascular and all-cause mortality: Results of the SPACE study.

BACKGROUND: Environmental exposures account for a growing proportion of global mortality. Large cohort studies are needed to characterize the independent impact of environmental exposures on mortality in low-income settings. METHODS: We collected data on individual and environmental risk factors for a multiethnic cohort of 50,045 individuals in a low-income region in Iran. Environmental risk factors included: ambient fine particular matter air pollution; household fuel use and ventilation; proximity to traffic; distance to percutaneous coronary intervention (PCI) center; socioeconomic environment; population density; local land use; and nighttime light exposure. We developed a spatial survival model to estimate the independent associations between these environmental exposures and all-cause and cardiovascular mortality. FINDINGS: Several environmental factors demonstrated associations with mortality after adjusting for individual risk factors. Ambient fine particulate matter air pollution predicted all-cause mortality (per µg/m3, HR 1.20, 95% CI 1.07, 1.36) and cardiovascular mortality (HR 1.17, 95% CI 0.98, 1.39). Biomass fuel use without chimney predicted all-cause mortality (reference = gas, HR 1.23, 95% CI 0.99, 1.53) and cardiovascular mortality (HR 1.36, 95% CI 0.99, 1.87). Kerosene fuel use without chimney predicted all-cause mortality (reference = gas, HR 1.09, 95% CI 0.97, 1.23) and cardiovascular mortality (HR 1.19, 95% CI 1.01, 1.41). Distance to PCI center predicted all-cause mortality (per 10km, HR 1.01, 95% CI 1.004, 1.022) and cardiovascular mortality (HR 1.02, 95% CI 1.004, 1.031). Additionally, proximity to traffic predicted all-cause mortality (HR 1.13, 95% CI 1.01, 1.27). In a separate validation cohort, the multivariable model effectively predicted both all-cause mortality (AUC 0.76) and cardiovascular mortality (AUC 0.81). Population attributable fractions demonstrated a high mortality burden attributable to environmental exposures. INTERPRETATION: Several environmental factors predicted cardiovascular and all-cause mortality, independent of each other and of individual risk factors. Mortality attributable to environmental factors represents a critical opportunity for targeted policies and programs.

Level and trend of total plasma cholesterol in national and subnational of Iran: a systematic review and age-spatio-temporal analysis from 1990 to 2016.

Purpose: We aimed to estimate the level and trend of plasma cholesterol and raised total cholesterol (TC > 200 mg/dl) prevalence at national and subnational level of Iran. Methods: Nine national surveys and 27 studies, encompassing 3,505 unique points on over 500,000 adults, aged > 25 years with a report of laboratory measurement of TC were found. Age-spatio-temporal model and Gaussian Process Regression were used to estimate mean TC for each sex, 5-year age groups, and 31 provinces from 1990 to 2016. Results: At national level, age-standardized prevalence of TC > 200 mg/dL has decreased from 57·2%(53·3-61·1) to 22·4%(20·5-24·3) in women and 53·2%(49·1-57·3) to 18·0%(16·4-19·6) in men. TC distribution presented a condensation between 170-200 mg/dL. At subnational level, decreasing and converging patterns of raised TC prevalence were detected. Conclusion: The decrease in raised TC is likely the result of statin widespread use, food industry improvements, and the expanded primary health care. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01052-w.

Multimorbidity and associations with clinical outcomes in a middle-aged population in Iran: a longitudinal cohort study.

BACKGROUND: As the populations of lower-income and middle-income countries age, multimorbidity is increasing, but there is little information on its long-term consequences. We aimed to show associations between multimorbidity and outcomes of mortality and hospitalisation in Iran, a middle-income country undergoing rapid economic transition. METHODS: We conducted a secondary analysis of longitudinal data collected in the Golestan Cohort Study. Data on demographics, morbidities and lifestyle factors were collected at baseline, and information on hospitalisations or deaths was captured annually. Logistic regression was used to analyse the association between baseline multimorbidity and 10-year mortality, Cox-proportional hazard models to measure lifetime risk of mortality and zero-inflation models to investigate the association between hospitalisation and multimorbidity. Multimorbidity was classified as ≥2 conditions or number of conditions. Demographic, lifestyle and socioeconomic variables were included as covariables. RESULTS: The study recruited 50 045 participants aged 40-75 years between 2004 and 2008, 47 883 were available for analysis, 416 (57.3%) were female and 12 736 (27.94%) were multimorbid. The odds of dying at 10 years for multimorbidity defined as ≥2 conditions was 1.99 (95% CI 1.86 to 2.12, p<0.001), and it increased with increasing number of conditions (OR of 3.57; 95% CI 3.12 to 4.08, p<0.001 for ≥4 conditions). The survival analysis showed the hazard of death for those with ≥4 conditions was 3.06 (95% CI 2.74 to 3.43, p<0.001). The number of hospital admissions increased with number of conditions (OR of not being hospitalised of 0.36; 95% CI 0.31 to 0.52, p<0.001, for ≥4 conditions). CONCLUSION: The long-terms effects of multimorbidity on mortality and hospitalisation are similar in this population to those seen in high-income countries.

Comparison of laboratory-based and non-laboratory-based WHO cardiovascular disease risk charts: a population-based study.

BACKGROUND: Determining the risk of Cardiovascular Disease (CVD) is a necessity for timely preventive interventions in high-risk groups. However, laboratory testing may be impractical in countries with limited resources. This study aimed at comparison and assessment of the agreement between laboratory-based and non-laboratory-based WHO risk charts models. METHODS: This study was performed using the baseline data of 8138 participants in the pars cohort study who had no history of CVD and stroke. The updated 2019 WHO model was used to determine the 10-year fatal and non-fatal CVD risks. In general, there are two types of new WHO risk prediction models for CVD. The scores were determined based on age, sex, smoking status, diabetes, Systolic Blood Pressure (SBP), and total cholesterol for the laboratory-based model and age, sex, smoking status, SBP, and Body Mass Index (BMI) for the non-laboratory-based model. The agreement of these two models was determined via kappa statistics for the classified risk (low: < 10%, moderate: 10-< 20%, high: ≥ 20%). Correlation coefficients (r) and scatter plots was used for correlation between scores. RESULTS: The results revealed very strong correlation coefficients for all sex and age groups (r = 0.84 for males < 60 years old, 0.93 for males ≥ 60 years old, 0.85 for females < 60 years old, and 0.88 for females ≥ 60 years old). In the laboratory-based model, low, moderate, and high risks were 76.10%, 18.17%, and 5.73%, respectively. These measures were respectively obtained as 77.00%, 18.08%, and 4.92% in the non-laboratory-based model. Based on risk classification, the agreement was substantial for males < 60 years old and for both males and females aged ≥ 60 years (kappa values: 0.79 for males < 60 years old, 0.65 for males ≥ 60 years old, and 0.66 for females ≥ 60 years old) and moderate for females < 60 years old (kappa = 0.46). CONCLUSIONS: The non-laboratory-based risk prediction model, which is simple, inexpensive, and non-invasive, classifies individuals almost identically to the laboratory-based model. Therefore, in countries with limited resources, these two models can be used interchangeably.

Prevalence and predictors of low back pain among the Iranian population: Results from the Persian cohort study.

BACKGROUND AND OBJECTIVES: Low back pain (LBP) is a common health condition in populations. Limited large-scale population-based studies evaluated the prevalence and predictors of LBP in developing countries. This study aimed to evaluate the prevalence and factors associated with LBP among the Iranian population. METHODS: We used baseline information from the Prospective Epidemiological Research Studies in Iran (PERSIAN), including individuals from 16 provinces of Iran. LBP was defined as the history of back pain interfering with daily activities for more than one week during an individual's lifetime. Various factors hypothesized to affect LBP, such as age, sex, marital status, educational status, ethnicity, living area, employment status, history of smoking, body mass index (BMI), physical activity, sleep duration, wealth score, history of joint pain, and history of morning stiffness in the joints were evaluated. RESULTS: In total, 163770 Iranians with a mean age of 49.37 (SD = 9.15) were included in this study, 44.8% of whom were male. The prevalence of LBP was 25.2% among participants. After adjusting for confounders, the female gender [OR:1.244(1.02-1.50)], middle and older ages [OR:1.23(1.10-1.33) and OR:1.13(1.07-1.42), respectively], being overweight or obese [OR:1.13(1.07-1.19) and OR:1.21(1.16-1.27), respectively], former and current smokers (OR:1.25(1.16-1.36) and OR:1.28(1.17-1.39), respectively], low physical activity [OR:1.07(1.01-1.14)], and short sleep duration [OR: 1.09(1.02-1.17)] were significantly associated with LBP. CONCLUSION: In this large-scale study, we found the lifetime prevalence of LBP to be lower among the Iranian population in comparison to the global prevalence of LBP; further studies are warranted to evaluate the causality of risk factors on LBP.

Levels and Trends of Maternal Mortality and Morbidity by Cause in North Africa and Middle East, 1990 to 2019: An Analysis for the Global Burden of Disease Study 2019.

BACKGROUND: Since 1990, the maternal mortality significantly decreased at global scale as well as the North Africa and Middle East. However, estimates for mortality and morbidity by cause and age at national scale in this region are not available. METHODS: This study is part of the Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2019. Here we report maternal mortality and morbidity by age and cause across 21 countries in the region from 1990 to 2019. RESULTS: Between 1990 and 2019, maternal mortality ratio (MMR) dropped from 148.8 (129.6-171.2) to 94.3 (73.4-121.1) per 100000 live births in North Africa and Middle East. In 1990, MMR ranged from 6.0 (5.3-6.8) in Kuwait to 502.9 (375.2-655.3) per 100000 live births in Afghanistan. Respective figures for 2019 were 5.1 (4.0-6.4) in Kuwait to 269.9 (195.8-368.6) in Afghanistan. Percentages of deaths under 25 years was 26.0% in 1990 and 23.8% in 2019. Maternal hemorrhage, indirect maternal deaths, and other maternal disorders rank 1st to 3rd in the entire region. Ultimately, there was an evident decrease in MMR along with increase in socio-demographic index from 1990 to 2019 in all countries in the region and an evident convergence across nations. CONCLUSION: MMR has significantly declined in the region since 1990 and only five countries (Afghanistan, Sudan, Yemen, Morocco, and Algeria) out of 21 nations didn't achieve the Sustainable Development Goal (SDG) target of 70 deaths per 100000 live births in 2019. Despite the convergence in trends, there are still disparities across countries.

Neonate, Infant, and Child Mortality by Cause in Provinces of Iran: An Analysis for the Global Burden of Disease Study 2019.

BACKGROUND: Since 1990, neonatal, infant, and child mortality has substantially decreased in Iran. However, estimates for mortality by cause at subnational scale are not available. METHODS: This study is part of the Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2019. Here we report the number and rates of neonate, infant, and child deaths by cause across provinces of Iran from 1990 to 2019. RESULTS: Between 1990 and 2019, the neonatal mortality rate per 1000 live births decreased from 31.8 (95% UI: 28.1-35.5) to 6.8 (6.1-7.4). The child mortality rates decreased from 71.2 (63.6-79.1) to 11.1 (10.2-12.0) per 1000 live births. Mortality rates among neonates per 1000 live births ranged from 3.1 (2.6-3.7) to 10.0 (9.2-10.8) across provinces in 2019. Child mortality rate per 1000 live births ranged from 5.5 (4.6-6.5) to 17.9 (16.4-19.4) across provinces in 2019. Neonatal disorders, congenital birth defects, and lower respiratory infections were the three main causes of mortality in almost all provinces of Iran. The majority of neonatal disorders were due to neonatal preterm birth and neonatal asphyxia, trauma, and infections. The trends of mortality across provinces from 1990 to 2019 were converging and decreased along with increase in sociodemographic index (SDI). CONCLUSION: All provinces achieved the Sustainable Development Goal 3.2 of neonatal mortality less than 12 and child mortality less than 25 per 1000 live births. However, disparities still exist across provinces, specifically in low-SDI provinces.

Maternal Mortality and Morbidity by Cause in Provinces of Iran, 1990 to 2019: An Analysis for the Global Burden of Disease Study 2019.

BACKGROUND: Since 1990, maternal mortality ratio (MMR) has significantly decreased in Iran. However, estimates for mortality and morbidity by cause at subnational scale are not available. METHODS: This study is part of the Global Burden of Diseases study (GBD) 2019. Here we report maternal mortality and morbidity by age and cause across 31 provinces of Iran from 1990 to 2019. RESULTS: Since 1990, MMR declined from 44.5 (95% UI: 38.6-50.1) to 15.9 (14.7-17.3) per 100000 live births in Iran. In 1990 MMR ranged from 18.5 (11.2-26.4) to 76.9 (38.4-114.7) per 100000 live births across provinces. Respective figures for 2019 were 7.1 (5.2-9.3) to 34.0 (25.1-44.7) per 100000 live births. In 2019, MMR was higher in young women (aged 10 to 14) and older women (aged 45 or more). Percentages of deaths under 25 years was 24.8% in 1990 and 16.0% in 2019. There was remarkable decline in years lost due to premature death (YLL) rates from 1990 to 2019. While the decline was modest for years lived with disability (YLD) rates. Indirect maternal deaths and other maternal deaths ranked first or second in almost all provinces. Ultimately, there was an evident decrease in MMR along with increase in socio-demographic Index (SDI) from 1990 to 2019 in all provinces and an evident convergence across provinces. CONCLUSION: MMR has declined to levels much lower than Sustainable Development Goals in all provinces. Although there was a convergence in trends, there are still disparities across provinces. The decline in disabilities caused by maternal disorders is not as significant as mortality, which needs further actions.

Neonate, Infant, and Child Mortality in North Africa and Middle East by Cause: An Analysis for the Global Burden of Disease Study 2019.

BACKGROUND: During the past three decades, neonate, infant, and child mortality declined in North Africa and Middle East. However, there is substantial heterogeneity in mortality rates across countries. METHODS: This study is part of the Global Burden of Diseases study (GBD) 2019. We report the number as well as mortality rates for neonates, infants, and children by cause across 21 countries in the region since 1990. RESULTS: Between 1990 and 2019, the neonate mortality rate in the region declined from 31.9 (29.8, 34.0) to 12.2 (11.1, 13.3) per 1000 live births. Respective figures for under 5 mortality rates (U5MRs) were 79.1 (75.7, 82.7) in 1990 and 24.4 (22.3, 26.7) per 1000 live births in 2019. The majority of deaths among children under 5 years were due to under 1 year deaths: 75.9% in 1990 and 81.8% in 2019. Mortality rates in males were higher than females. The mortality rate among neonates ranged from 2.4 (2.1, 2.6) per 1000 live births in Bahrain to 25.0 (21.6, 28.4) in Afghanistan in 2019. Similarly, in 2019, the U5MR ranged from 5.0 (4.2-6.0) per 1000 live births in United Arab Emirates to 55.3 (47.9-63.5) in Afghanistan. Neonatal disorders, congenital birth defects, and lower respiratory infections were the three main causes of neonate, infant, and child mortality in almost all countries in the region. CONCLUSION: In 2019, most countries in this region have achieved the SDG targets for neonate and child mortality. However, there is still substantial heterogeneity across countries.

Prediction of Cardiovascular Disease Mortality in a Middle Eastern Country: Performance of the Globorisk and Score Functions in Four Population-Based Cohort Studies of Iran.

BACKGROUND: Considering the importance of cardiovascular disease (CVD) risk prediction for healthcare systems and the limited information available in the Middle East, we evaluated the SCORE and Globorisk models to predict CVD death in a country of this region. METHODS: We included 24 427 participants (11 187 men) aged 40-80 years from four population-based cohorts in Iran. Updating approaches were used to recalibrate the baseline survival and the overall effect of the predictors of the models. We assessed the models' discrimination using C-index and then compared the observed with the predicted risk of death using calibration plots. The sensitivity and specificity of the models were estimated at the risk thresholds of 3%, 5%, 7%, and 10%. An agreement between models was assessed using the intra-class correlation coefficient (ICC). We applied decision analysis to provide perception into the consequences of using the models in general practice; for this reason, the clinical usefulness of the models was assessed using the net benefit (NB) and decision curve analysis. The NB is a sensitivity penalized by a weighted false positive (FP) rate in population level. RESULTS: After 154 522 person-years of follow-up, 437 cardiovascular deaths (280 men) occurred. The 10-year observed risks were 4.2% (95% CI: 3.7%-4.8%) in men and 2.1% (1.8-2%.5%) in women. The c-index for SCORE function was 0.784 (0.756-0.812) in men and 0.780 (0.744-0.815) in women. Corresponding values for Globorisk were 0.793 (0.766- 0.820) and 0.793 (0.757-0.829). The deviation of the calibration slopes from one reflected a need for recalibration; after which, the predicted-to-observed ratio for both models was 1.02 in men and 0.95 in women. Models showed good agreement (ICC 0.93 in men, and 0.89 in women). Decision curve showed that using both models results in the same clinical usefulness at the risk threshold of 5%, in both men and women; however, at the risk threshold of 10%, Globorisk had better clinical usefulness in women (Difference: 8%, 95% CI: 4%-13%). CONCLUSION: Original Globorisk and SCORE models overestimate the CVD risk in Iranian populations resulting in a high number of people who need intervention. Recalibration could adopt these models to precisely predict CVD mortality. Globorisk showed better performance clinically, only among high-risk women.

An office-based cardiovascular prediction model developed and validated in cohort studies of a middle-income country.

OBJECTIVE: Prediction models for cardiovascular disease (CVD) mortality come from high-income countries, comprising laboratory measurements, not suitable for resource-limited countries. This study aims to develop and validate a non-laboratory model to predict CVD mortality in a middle-income setting. STUDY DESIGN AND SETTING: We used data of population aged 40-80 years from three cohort studies: Tehran Lipid and Glucose Study (n = 5160), Isfahan Cohort Study (n = 4350), and Golestan Cohort Study (n = 45,500). Using Cox proportional hazard models, we developed prediction models for men and women, separately. Cross-validation and bootstrapping procedures were applied. The models' discrimination and calibration were assessed by concordance statistic (C-index) and calibration plot, respectively. We calculated the models' sensitivity, specificity and net benefit fraction in a threshold probability of 5%. RESULTS: The 10-year CVD mortality risks were 5.1% (95%CI: 4.8-5.5) in men and 3.1% (95%CI: 2.9%-3.3%) in women. The optimism-corrected performance of the model was c = 0.774 in men and c = 0.798 in women. The models showed good calibration in both sexes, with a predicted-to-observed ratio of 1.07 in men and 1.09 in women. The sensitivity was 0.76 in men and 0.66 in women. The net benefit fraction was higher in men compared to women (0.46 vs. 0.35). CONCLUSION: A low-cost model can discriminate well between low- and high-risk individuals, and can be used for screening in low-middle income countries.