Estimated glomerular filtration rate slope and risk of primary and secondary major adverse cardiovascular events and heart failure hospitalization in people with type 2 diabetes: An analysis of the EXSCEL trial.

AIM: The decline in estimated glomerular filtration rate (eGFR), a significant predictor of cardiovascular disease (CVD), occurs heterogeneously in people with diabetes because of various risk factors. We investigated the role of eGFR decline in predicting CVD events in people with type 2 diabetes in both primary and secondary CVD prevention settings. MATERIALS AND METHODS: Bayesian joint modelling of repeated measures of eGFR and time to CVD event was applied to the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial to examine the association between the eGFR slope and the incidence of major adverse CV event/hospitalization for heart failure (MACE/hHF) (non-fatal myocardial infarction, non-fatal stroke, CV death, or hospitalization for heart failure). The analysis was adjusted for age, sex, smoking, systolic blood pressure, baseline eGFR, antihypertensive and lipid-lowering medication, diabetes duration, atrial fibrillation, high-density cholesterol, total cholesterol, HbA1c and treatment allocation (once-weekly exenatide or placebo). RESULTS: Data from 11 101 trial participants with (n = 7942) and without (n = 3159) previous history of CVD were analysed. The mean ± SD eGFR slope per year in participants without and with previous CVD was -0.68 ± 1.67 and -1.03 ± 2.13 mL/min/1.73 m2, respectively. The 5-year MACE/hHF incidences were 7.5% (95% CI 6.2, 8.8) and 20% (95% CI 19, 22), respectively. The 1-SD decrease in the eGFR slope was associated with increased MACE/hHF risks of 48% (HR 1.48, 95% CI 1.12, 1.98, p = 0.007) and 33% (HR 1.33, 95% CI 1.18,1.51, p < 0.001) in participants without and with previous CVD, respectively. CONCLUSIONS: eGFR trajectories over time significantly predict incident MACE/hHF events in people with type 2 diabetes with and without existing CVD, with a higher hazard ratio for MACE/hHF in the latter group.

Association of Biomarkers for Dyslipidemia, Inflammation, and Oxidative Stress with Endothelial Dysfunction in Obese Youths: A Case-Control Study.

Objective: The United Arab Emirates (UAE), with its characteristic local population, geography, and history, presents several risk factors for cardiovascular diseases (CVDs) in obese individuals. Obesity and its associated complications, including diabetes, atherogenic dyslipidemia, and CVDs leading to significant health risks. In the present study, "Youths" defined as young people between 18 and 22 years. We assessed dyslipidemia, inflammation, and oxidative stress biomarker levels and their association with endothelial dysfunction (ED) in both overweight/obese and normal weight youths of UAE. Methods: There were 160 youths with overweight/obese (BMI ≥ 25 kg/m2) patients and healthy age- and sex-matched normal weight (BMI ≤ 24.9 kg/m2) as controls participated in this study. The anthropometric data and blood samples were collected to assess the biomarkers for dyslipidemia, inflammation, oxidative stress, ED from all the youths. Results: The overall mean age and male-to-female ratio were 20±1.5years and 1.0:1.2, respectively. There was statistically significant difference in HDL-C (p<0.001), triglycerides (TG) (p<0.001), ApoA (p=0.002), ApoB/ApoA ratio (p=0.009) between the overweight/obese and normal weight youths. Among, inflammatory markers: hs-CRP, IL-6, TNF-α also showed significant p<0.001 and oxidative stress markers: DNA/RNA Damage, catalase and nitric oxide (NO) showed significant p<0.001 between groups. Spearman correlation of ED markers with lipid profile markers showed Vitamin C levels positively correlated with HDL-C (p<0.001) and negatively correlated with glucose (p<0.001). ICAM-1showed significant negative correlation with HDL-C (p<0.01) and ApoA (p<0.001) but positive correlation with TG (p<0.01) and HbA1c (p<0.001) among groups. Spearman correlation of ED markers with inflammatory/oxidative stress biomarkers showed Vitamin C levels negatively correlated with ferritin (p < 0.001), NO (p < 0.001), GGT (p < 0.001), and ALT (p < 0.001) levels. The ICAM-1showed significant positive correlation with hs-CRP (p < 0.01), IL-6 (p < 0.001), TNF-α (p < 0.01), GGT (p < 0.05), and ALT (p < 0.05) in both groups. Conclusion: This study revealed a strong link between the biomarkers of dyslipidemia, inflammation, and oxidative stress with ED in overweight/obese patients. This study might be used to predict future cardiovascular events in this population.

Lipid profile, inflammatory biomarkers, endothelial dysfunction, and heart rate variability in adolescents with type 1 diabetes. A case-control study among UAE population.

Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the chronic inflammation and cause of endothelial dysfunction (ED). Heart rate variability (HRV) is a marker of sympathetic and parasympathetic autonomic nervous system dysfunction. We investigated the association of lipid profile, inflammatory biomarkers, endothelial dysfunction, and heart rate variability in adolescents with T1DM among UAE population. Method: In this case-control study we recruited 126 adolescents (13-22 years) from Abu Dhabi, UAE (United Arab Emirates). Demographic, anthropometric, blood and urine samples were collected after an overnight fasting. HRV measurements were determined per Task Force recommendations. Independent t-test or Mann-Whitney U test and Pearson's Chi-squared test were used to compare groups. Adjusted conditional logistic regression model was used to identify the determinants independently associated with T1DM. Results: The mean ages in control (n = 47) and patient (n = 79) groups were 17.5 ± 4.6 and 18.6 ± 4.8 years, respectively. A family history of diabetes and waist and hip circumferences significantly differed between the groups (p = 0.030 and 0.010). The patients with T1DM exhibited significantly higher levels of atherogenic markers than control. Endothelial dysfunction biomarkers such as levels of sICAM-1 (p < 0.001), adiponectin (p < 0.001) and 25-hydroxyvitamin D (p < 0.001) were significantly different in the control group compared with those in the T1DM group. There was a significant difference in SDNN intervals, NN50, pNN50, and SD1/SD2 among the two groups. In adjusted analysis, total cholesterol (adjusted Odds Ratio (aOR): 2.78, 95 % CI:1.37-5.64; p = 0.005), LDL (2.66, 95%CI:1.19-5.92; p = 0.017), and triglycerides (5.51, 95%CI:1.57-19.41; p = 0.008) were significantly associated with developing T1DM. The HRV indicators were significantly associated with decrease odds of T1DM after controlling for SBP, BMI, and family history of DM. Conclusion: In this study, adolescents with T1DM showed a significant association with lipid profile, ED, and HRV compared with controls. Thus, an early attention to diabetes control is required to reduce the risk of cardiac autonomic neuropathy leading to various cardiovascular diseases.

Predictive performance of machine learning compared to statistical methods in time-to-event analysis of cardiovascular disease: a systematic review protocol.

BACKGROUND: Globally, cardiovascular disease (CVD) remains the leading cause of death, warranting effective management and prevention measures. Risk prediction tools are indispensable for directing primary and secondary prevention strategies for CVD and are critical for estimating CVD risk. Machine learning (ML) methodologies have experienced significant advancements across numerous practical domains in recent years. Several ML and statistical models predicting CVD time-to-event outcomes have been developed. However, it is not known as to which of the two model types-ML and statistical models-have higher discrimination and calibration in this regard. Hence, this planned work aims to systematically review studies that compare ML with statistical methods in terms of their predictive abilities in the case of time-to-event data with censoring. METHODS: Original research articles published as prognostic prediction studies, which involved the development and/or validation of a prognostic model, within a peer-reviewed journal, using cohort or experimental design with at least a 12-month follow-up period will be systematically reviewed. The review process will adhere to the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies checklist. ETHICS AND DISSEMINATION: Ethical approval is not required for this review, as it will exclusively use data from published studies. The findings of this study will be published in an open-access journal and disseminated at scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42023484178.

Temporal trends of hemoglobin among pregnant women: The Mutaba'ah study.

BACKGROUND: Low hemoglobin (Hb) level is a leading cause of many adverse pregnancy outcomes. Patterns of changes in Hb levels during pregnancy are not well understood. AIM: This study estimated Hb levels, described its changing patterns across gestational trimesters, and identified factors associated with these changes among pregnant women. MATERIALS AND METHODS: Data from the ongoing maternal and child health cohort study-The Mutaba'ah Study, was used (N = 1,120). KML machine learning algorithm was applied to identify three distinct cluster trajectories of Hb levels between the first and the third trimesters. Descriptive statistics were used to profile the study participants. Multinomial multivariable logistic regression was employed to identify factors associated with change patterns in Hb levels. RESULTS: The three identified clusters-A, B and C-had, respectively, median Hb levels (g/L) of 123, 118, and 104 in the first trimester and 119, 100, and 108 in the third trimester. Cluster 'A' maintained average normal Hb levels in both trimesters. Cluster 'B', on average, experienced a decrease in Hb levels below the normal range during the third trimester. Cluster 'C' showed increased Hb levels in the third trimester but remained, on average, below the normal range in both trimesters. Pregnant women with higher gravida, diabetes mellitus (type 1 or 2), nulliparity or lower level of education were more likely to be in cluster 'B' than the normal cluster 'A'. Pregnant women who reported using iron supplements before pregnancy or those with low levels of education. were more likely to be in cluster 'C' than the normal cluster 'A'. CONCLUSION: The majority of pregnant women experienced low Hb levels during pregnancy. Changes in Hb levels during pregnancy were associated with parity, gravida, use of iron before pregnancy, and the presence of diabetes mellitus (type 1 or 2).

Incidence of thyroid cancer in Abu Dhabi, UAE: A registry-based study.

Context: Thyroid cancer is the most common endocrine malignancy. It is ranked second among females of the Gulf Cooperation Council States and the sixth most common cancer among the United Arab Emirates population. Aims: We herein describe the incidence and distribution of different types of thyroid cancers and the demographic features of patients diagnosed with thyroid cancer in the Emirate of Abu Dhabi. Settings and Design: The study design was Abu Dhabi cancer registry and retrospective chart review. Subjects and Methods: This is a retrospective cancer registry description of patients with the different types of thyroid cancers diagnosed between January 2012 and December 2015 in the Emirate of Abu Dhabi. The incidence of thyroid cancer throughout the study period was calculated. Gender, age, ethnicity, and type of thyroid cancer were described. Statistical Analysis Used: Descriptive statistics of patients' characteristics are reported as means (standard deviation) for continuous variables and total and relative frequencies (percentage) for categorical variables. Results: The incidence of thyroid cancer was found to increase annually, reaching 7.9 cases per 100,000 population in 2015. A total of 603 patients were diagnosed with thyroid cancer in the Emirate of Abu Dhabi from 2012 to 2015. Of these, 431 (71.5%) were women and 172 (28.5%) were men. The overall mean age at diagnosis was 40.2 years. Over a third of the patients were between 30 and 39 years. The classical papillary thyroid cancer type was found in 67.7% of cases. Conclusions: A substantial increase in thyroid cancer rates was found between 2012 and 2015. The majority of thyroid cancer cases were diagnosed in women between the ages of 30 and 39 years. Classical papillary thyroid cancer was the most common type.

Joint longitudinal and time-to-event modelling compared with standard Cox modelling in patients with type 2 diabetes with and without established cardiovascular disease: An analysis of the EXSCEL trial.

AIM: To demonstrate the gain in predictive performance when cardiovascular disease (CVD) risk prediction tools (RPTs) incorporate repeated rather than only single measurements of risk factors. MATERIALS AND METHODS: We used data from the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial to compare the quality of predictions of future major adverse cardiovascular events (MACE) with the Cox proportional hazards model (using single values of risk factors) compared to the Bayesian joint model (using repeated measures of risk factors). The risk of MACE was calculated in patients with type 2 diabetes with and without established CVD. We assessed the predictive ability of the following cardiovascular risk factors: glycated haemoglobin, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides, estimated glomerular filtration rate, low-density lipoprotein cholesterol (LDL-C), total cholesterol, and systolic blood pressure (SBP) using the time-dependent area under the receiver-operating characteristic curve (aROC) for discrimination and the time-dependent Brier score for calibration. RESULTS: In participants without history of CVD, the aROC of SBP increased from 0.62 to 0.69 when repeated rather than only single measurements of SBP were incorporated into the predictive model. Similarly, the aROC increased from 0.67 to 0.80 when repeated rather than only single measurements of both SBP and LDL-C were incorporated into the predictive model. For all other investigated cardiovascular risk factors, the measures of discrimination and calibration both improved when using the joint model as compared to the Cox proportional hazards model. The improvement was evident in participants with and without history of CVD but was more pronounced in the latter group. CONCLUSIONS: The analysis demonstrates that the joint modelling approach, considering trajectories of cardiovascular risk factors, provides superior predictive performance compared to standard RPTs that use only a single timepoint.

The prevalence and correlates of depression among patients with chronic diseases in the United Arab Emirates.

BACKGROUND: Chronic diseases constitute a major public health problem in the United Arab Emirates (UAE) and are the leading cause of mortality and morbidity. Chronic diseases have been found to be associated with an increased prevalence of depression and depressive symptoms. Depression can have detrimental effect on the prognosis of the disease and quality of life in patients. AIMS AND OBJECTIVES: This study aimed to estimate the prevalence and correlates of depression in a sample of patients suffering from chronic disease in Al-Ain city, UAE. MATERIALS AND METHODS: A cross-sectional survey based study was conducted with 417 participants recruited from seven primary health care centers of Al-Ain city. Men and women aged 18 years and above suffering from chronic disease filled the Patient Health Questionnaire (PHQ-9). Univariate and multivariable logistic regressions were performed on the collected data to investigate correlates of different factors with depression. Data was analyzed using SPSS (version 26). The study was approved by Ambulatory Healthcare Services (AHS) Human Ethics Research Committee. RESULTS: The majority 62.41% (n = 254) of the sample were females, 57.97% (n = 240) aged above 55 years and with a median (Q25, Q75) duration of chronic disease of 8 (4, 15) years. The prevalence of depression was 21.1% (95% CI: 17.5%-25.3%). With severe depression was in 1.7% and mild-moderate in 34.7% of the participants. Depression severity was statistically significantly associated with increasing age (p = 0.006), low level of education (p<0.001), presence of asthma (p = 0.007) and heart disease (p = 0.013). Unadjusted logistic regression reported that presence of depression was significantly associated with female gender (cOR = 1.8, [95% CI; 1.1-3.1], p = 0.025), and presence of chronic kidney disease (cOR = 4.9, [95% CI; 1.3-20.2], p = 0.020) and heart disease (cOR = 2.9, [95% CI; 1.6-5.4], p = 0.001) longer duration of disease in years (cOR = 1.04, [95% CI; 1.01-1.07], p = 0.003). However, in the adjusted logistic regression analysis, participants with heart disease (aOR = 2.8, [95% CI; 1.4-5.5], p = 0.004), and with longer duration of disease (aOR = 1.04, [1.01-1.07], p = 0.014) remained significantly associated statistically with higher chance of having depression. CONCLUSION: The prevalence of depression was quite high and the study highlights for health care professionals and policy makers, the importance of mental health support as part of a comprehensive management plan for patients with chronic diseases. A multidisciplinary comprehensive program will improve the long-term outcomes of these patients. Patients with chronic diseases may need more support and counseling at primary health care levels.

Breast cancer survival and its prognostic factors in the United Arab Emirates: A retrospective study.

BACKGROUND: Data on breast cancer survival and its prognostic factors are lacking in the United Arab Emirates (UAE). Sociodemographic and pathologic factors have been studied widely in western populations but are very limited in this region. This study is the first to report breast cancer survival and investigate prognostic factors associated with its survival in the UAE. METHODS: This is a retrospective cohort study involving 988 patients who were diagnosed and histologically confirmed with breast cancer between January 2008 and December 2012 at Tawam hospital, Al Ain, UAE. Patient were followed from the date of initial diagnosis until the date of death from any cause, lost-to-follow up or the end of December 2018. The primary outcome is overall survival (OS). The Kaplan-Meier method was used to estimate the survival curve along with the 2- and 5-year survivals. Different group of patients categorized according to prognostic factors were compared using the log-rank test. Multiple Cox proportional hazards models was used to examine the impact of several prognostic factors on the overall survival. RESULTS: The median study follow-up was 35 months. Of the 988 patients, 62 had died during their follow-up, 56 were lost to follow-up and 870 were still alive at the end of the study. The average age of patients was 48 years. The majority of patients presented to the hospital with grade II or III, 24% with at least stage 3 and 9.2% had metastasis. The 2-year and 5-year survivals were estimated to 97% and 89% respectively. Results of the multiple Cox proportional hazard model show that tumor grade, and stage of cancer at presentation are jointly significantly associated with survival. CONCLUSION: The 2- and 5-year survival are within the norms compared to other countries. Significant clinical and pathological prognostic factors associated with survival were tumor grade, and the stage of cancer at presentation.

Admission levels of Soluble Urokinase Plasminogen Activator Receptor (suPAR) are Associated with the Development of Severe Complications in Hospitalised COVID-19 Patients: A Prospective Cohort Study.

OBJECTIVE: To examine the association between plasma levels of the soluble urokinase plasminogen activator receptor (suPAR) and the incidence of severe complications of COVID-19. METHODS: 403 RT-PCR-confirmed COVID-19 patients were recruited and prospectively followed-up at a major hospital in the United Arab Emirates. The primary endpoint was time from admission until the development of a composite outcome, including acute respiratory distress syndrome (ARDS), intensive care unit (ICU) admission, or death from any cause. Patients discharged alive were considered as competing events to the primary outcome. Competing risk regression was used to quantify the association between suPAR and the incidence of the primary outcome. RESULTS: 6.2% of patients experienced ARDS or ICU admission, but none died. Taking into account competing risk, the incidence of the primary outcome was 11.5% (95% confidence interval [CI], 6.7-16.3) in patients with suPAR levels >3.91 ng/mL compared to 2.9% (95% CI, 0.4-5.5) in those with suPAR ≤3.91 ng/mL. Also, an increase by 1 ng/mL in baseline suPAR resulted in a 58% rise in the hazard of developing the primary outcome (hazard ratio 1.6, 95% CI, 1.2-2.1, p = 0.003). CONCLUSION: suPAR has an excellent prognostic utility in predicting severe complications in hospitalised COVID-19 patients.

Hypertension Control and Guideline-Recommended Target Blood Pressure Goal Achievement at an Early Stage of Hypertension in the UAE.

(1) Background: The present study aimed to assess the changes in blood pressure (BP) within the first 6 months of treatment initiation in a newly treated hypertensive cohort and to identify the factors that are associated with achieving the target BP recommended by the American (ACC/AHA, 2017), European (ESC/ESH, 2018), United Kingdom (NICE, 2019), and International Society of Hypertension (ISH, 2020) guidelines. (2) Methods: We analyzed 5308 incident hypertensive outpatients across Abu Dhabi, United Arab Emirates (UAE), in 2017; each patient was followed up for 6 months. Hypertension was defined as a BP of 130/80 mmHg according to the ACC/AHA guidelines and 140/90 mmHg according to the ESC/ESH, NICE, and ISH guidelines. Multiple logistic regression was used to identify factors associated with achieving the guideline-recommended BP targets. (3) Results: At baseline, the mean BP was 133.9 ± 72.9 mmHg and 132.7 ± 72.5 mmHg at 6 months. The guideline-recommended BP targets were 39.5%, 43%, 65.6%, and 40.8%, according to the ACC/AHA, ESC/ESH, NICE, and ISH guidelines, respectively. A BMI of <25 kg/m2 was associated with better BP control according to the ACC/AHA (odds ratio (OR) = 1.26; 95% confidence interval (CI) = 1.07-1.49), ESC/ESH (OR = 1.27; 95% CI = 1.08-1.50), and ISH guidelines (OR = 1.22; 95% CI = 1.03-1.44). Hypertension treated in secondary care settings was more likely to achieve the BP targets recommended by the ACC/AHA (1.31 times), ESC/ESH (1.32 times), NICE (1.41 times), and ISH (1.34 times) guidelines. (4) Conclusions: BP goal achievement was suboptimal. BP control efforts should prioritize improving cardiometabolic goals and lifestyle modifications.

Agreement between cardiovascular disease risk assessment tools: An application to the United Arab Emirates population.

INTRODUCTION: Evidence regarding the performance of cardiovascular disease (CVD) risk assessment tools is limited in the United Arab Emirates (UAE). Therefore, we assessed the agreement between various externally validated CVD risk assessment tools in the UAE. METHODS: A secondary analysis of the Abu Dhabi Screening Program for Cardiovascular Risk Markers (AD-SALAMA) data, a large population-based cross-sectional survey conducted in Abu Dhabi, UAE during the period 2009 until 2015, was performed in July 2019. The analysis included 2,621 participants without type 2 Diabetes and without history of cardiovascular diseases. The CVD risk assessment tools included in the analysis were the World Health Organization for Middle East and North Africa Region (WHO-MENA), the systematic coronary risk evaluation for high risk countries (SCORE-H), the pooled cohort risk equations for white (PCRE-W) and African Americans (PCRE-AA), the national cholesterol education program Framingham risk score (FRAM-ATP), and the laboratory Framingham risk score (FRAM-LAB). RESULTS: The overall concordance coefficient was 0.50. The agreement between SCORE-H and PCRE-W, PCRE-AA, FRAM-LAB, FRAM-ATP and WHO-MENA, were 0.47, 0.39, 0.0.25, 0.42 and 0.18, respectively. PCRE-AA classified the highest proportion of participants into high-risk category of CVD (16.4%), followed by PCRE-W (13.6%), FRAM-LAB (6.9%), SCORE-H (4.5%), FRAM-ATP (2.7%), and WHO-MENA (0.4%). CONCLUSIONS: We found a poor agreement between various externally validated CVD risk assessment tools when applied to a large data collected in the UAE. This poses a challenge to choose any of these tools for clinical decision-making regarding the primary prevention of CVD in the country.