Behnam Heidari

Risk of coronary heart disease associated with metabolic syndrome and its individual components in Iranian subjects: A matched cohort study

BACKGROUND AND OBJECTIVES To evaluate the risk of coronary heart disease (CHD) associated with metabolic syndrome (MetS) and its individual components in a representative sample of diabetic and nondiabetic Iranians. Moreover, we aimed to define the most hazardous MetS components. METHODS Two cohorts consisting of 1737 nondiabetic and 2385 diabetic participants were followed for the first CHD event during 8.5 years (until December 2013). RESULTS MetS is defined as having 3 individual components associated with increased risk of CHD (hazard ratio [HR] for MetS: in the unadjusted were 2.85 [2.27-3.57] and in the fully adjusted model 1.80 [1.42-2.28]). MetS was associated with lower hazard of CHD in subjects older than 65 (HR: 1.50 vs. 3.47; P for interaction < .05) and in men (HR: 1.68 vs. 4.87; P for interaction < .05). Presence of 4 of 5 individual MetS components increased the risk of CHD associated with MetS as a constellation. The value of MetS is augmented in the presence of low high-density lipoprotein-cholesterol (HR: 5.74 [2.52-13.08]) versus its absence (HR 1.91 [1.33-2.75]), high triglycerides (HR: 3.39 [1.38-8.34] vs. 1.99 [1.40-2.82] in its absence) and elevated blood pressure (HR: 2.61 [1.43-4.76] vs. 1.80 [1.26-2.58] in its absence). CONCLUSIONS We address the value of MetS components in the prediction of CHD and in the absence of traditional risk factors. This study provides evidence for the synergistic effect of MetS components on the incidence of CHD.

Contribution of vitamin D deficiency to the risk of coronary heart disease in subjects with essential hypertension.

BACKGROUND Vitamin D deficiency is proposed as a risk factor for coronary heart disease (CHD). An inverse relation was observed between serum 25-Hydroxy-Vitamin-D level and incidence of hypertension. This study aimed to evaluate the predictive value of serum 25-Hydroxy-Vitamin-D in improvement of CHD risk-stratification in patients with hypertension. METHODS In this cohort, we followed 1586 patients with essential hypertension (1078 diabetic and 508 non-diabetic) for 8.5 years. Physician-adjudicated first hard CHD event was the primary outcome. Cox regression analysis was used to investigate the association between 25-Hydroxy-Vitamin-D quartiles and incident CHD. 25-Hydroxy-Vitamin-D was also added to the Framingham Risk Score (FRS) and Net-Reclassification-Improvement (NRI) and Integrated-Discriminant-Improvement (IDI) were used to examine improved reclassification. RESULTS During follow-up, 176 events were recorded. Patients in the lowest quartile of 25-Hydroxy-Vitamin-D experienced the most number of hard CHD events. A significant linear trend was observed in hazard ratios (HR) of incident hard CHD events in 25-Hydroxy-Vitamin-D quartiles which remained significant after multiple adjustments for conventional CHD risk-factors (HRs in full-adjusted model: 2.87 [1.76-4.70] for 1st quartile, 2.31 [1.39-3.83] for 2nd quartile and 1.87 [1.15-3.03] for 3rd quartile, compared with the highest quartile; p-for-trend<0.001). Addition of 25-Hydroxy-Vitamin-D to FRS could improve CHD risk-estimation (relative-IDI = 15%, p-value<0.001). Addition of 25-Hydroxy-Vitamin-D to FRS successfully reclassified 33% [18-49] of patients with hypertension among CHD risk groups (p-value<0.001). CONCLUSION We observed that serum 25-Hydroxy-Vitamin-D is independently associated with future hard CHD events and improves its prediction in patients with essential hypertension. Addition of serum 25-Hydroxy-Vitamin-D to CHD risk-estimation models may have additive values.

Non-linear contribution of serum vitamin D to symptomatic diabetic neuropathy: A case-control study.

AIMS Vitamin D deficiency has recently been speculated to be associated with increased risk of diabetes neuropathy (DN). The aim of this study was to evaluate the odds of symptomatic DN across serum vitamin D levels. METHODS All patients with DM were assessed using diabetic neuropathy symptoms and diabetic neuropathy examination score. Overall, 150 cases with DN and 600 controls were included. Serum 25-hydroxyvitamin D (25-OH-D) was measured to determine vitamin D status. RESULTS A non-linear association between 25-OH-D and suffering from symptomatic DN was observed which was extracted after stratifying the ORs across different serum 25-OH-D levels. When compared to individuals with 25-OH-D of 30-40 ng/mL, patients with deficient (<20 ng/mL) vitamin D levels had higher odds of having symptomatic DN (OR: 2.04, 95%CI: 0.99-4.02, P=0.054). Participants with vitamin D values of greater than 40 ng/mL were also more likely to exhibit symptomatic DN (fully adjusted OR: 4.29, 95%CI: 1.59-11.55). CONCLUSIONS We hypothesize a non-linear contribution of serum vitamin D to symptomatic DN occurrence, which emphasizes that administration of vitamin D should be monitored and evaluated more carefully, especially in patients with diabetes.

Diabetes Care in Iran: Where We Stand and Where We Are Headed

BACKGROUND The prevalence of diabetes has steadily increased in Iran from the time of the first published nationally representative survey in 1999 and despite efforts and strategies to reduce disease burden. OBJECTIVES The aim of the present review was to describe the current status of diabetes care in Iran. METHODS A selective review of the relevant literature, focusing on properly conducted studies, describing past and present diabetes care strategies, policies, and outcomes in Iran was performed. FINDINGS The quality of diabetes care has gradually improved as suggested by a reduction in the proportion of undiagnosed patients and an increase in affordability of diabetes medications. The National Program for Prevention and Control of Diabetes has proven successful at identifying high-risk individuals, particularly in rural and remote-access areas. Unfortunately, the rising tide of diabetes is outpacing these efforts by a considerable margin. CONCLUSIONS Substantial opportunities and challenges in the areas of prevention, diagnosis, and management of diabetes exist in Iran that need to be addressed to further improve the quality of care and clinical outcomes.

Mechanisms of anti-retroviral drug resistance: implications for novel drug discovery and development.

Anti-retroviral drug resistance evolves as an inevitable consequence of expanded combination Anti-retroviral Therapy (cART). According to each drug class, resistance mutations may occur due to the infidel nature of HIV reverse transcriptase (RT) and inadequate drug pressures. Correspondingly, resistance to Nucleoside Reverse Transcriptase Inhibitors (NRTIs) occurs due to incorporation impairment of the agent or its removal from the elongating viral DNA chain. With regard to Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), resistance mutations may alter residues of the RT hydrophobic pocket and demonstrate high level of cross resistance. However, resistance to Protease Inhibitors requires complex accumulation of primary and secondary mutations that substitute amino acids in proximity to the viral protease active site. Resistance to novel entry inhibitors may also evolve as a result of mutations that affect the interactions between viral glycoprotein and CD4 or the chemokine receptors. According to the current studies, future drug initiative programs should consider agents that possess higher genetic barrier toward resistance for ascertaining adequate drug efficacy among patients who have failed first-line regimens.

Diabetes in Iran: Prospective analysis from first nationwide diabetes report of National Program for Prevention and Control of Diabetes (NPPCD-2016)

We estimated proportions of different types of diabetes, comorbidities, treatment (the use of oral glucose-lowering agents and insulin), control (hyperglycemia, dyslipidemia and hypertension) and chronic microvascular and macrovascular complications among people with diabetes presenting to the tertiary-care academic diabetes outpatient clinics in Iran. This study is the prospective analysis of data (n = 30,202) from the registry of university-affiliated adult outpatient diabetes clinics in the country during 2015–2016. The proportions of type 1 diabetes, types 2 diabetes, and other types of diabetes were 11.4%, 85.5%, and 1.3%, respectively. The frequencies of drug-naivety, use of oral agents, insulin monotherapy and insulin combination therapy were 2.9%, 60.5%, 11.5%, and 25.1%, respectively. Around 13.2%, 11.9% and 43.3% of patients with diabetes had controlled hyperglycemia, hyperlipidemia and hypertension, respectively. The proportions of retinopathy, nephropathy, peripheral neuropathy, diabetic foot, and ischemic heart disease were 21.9%, 17.6%, 28.0%, 6.2%, and 23.9%, respectively. Despite the wide availability of medications and insulin coverage in Iran, the estimated national control of hyperglycemia, hyperlipidemia and hypertension (especially for young men and old women) remains subpar. The present study further suggests that the frequencies of chronic vascular complications among patients with diabetes are relatively high in Iran.

Abdominal obesity and gestational diabetes: the interactive role of magnesium

AIMS Magnesium is a cofactor for numerous metabolic enzymatic reactions. It is required for glucose utilization and insulin signaling. We compared plasma magnesium concentrations in pregnant women with and without abdominal obesity, and investigated the interactive roles of magnesium and obesity in the development of gestational diabetes mellitus (GDM). METHODS Pregnant women with and without abdominal obesity (n = 40 in each group) were followed during gestation. Oral glucose tolerance tests (OGTT) were performed at 24-28 weeks of pregnancy to diagnose GDM. Plasma glucose, insulin, triglycerides, high-sensitive C-reactive protein (hs-CRP), and malondialdehyde (MDA) were measured. The obesity-GDM relationship was investigated prospectively, and the magnesium-GDM relationship was analyzed on a cross-sectional basis. RESULTS Sixteen patients in the obese group and one in the control developed GDM. There were no differences in plasma magnesium levels between obese and control groups (p-value = 0.14), but significant differences between diabetic and non-diabetic patients (p-value = 0.05). Fourteen out of 17 diabetic patients had magnesium concentrations below the median. Increases in insulin, homeostatic model for insulin resistance, triglycerides, hs-CRP, MDA and second-hour blood glucose were more pronounced in those with both abdominal obesity and low-normal magnesium concentrations. In the Poisson regression model, obesity (relative risk = 20.6, p-value = 0.002), low-normal magnesium level (relative risk = 4.2, p-value = 0.009), and their interaction (p-value<0.001) were significant. CONCLUSION Abdominally obese patients with lower plasma magnesium are more likely to show abnormal OGTT results. Insulin resistance, inflammatory response and oxidative stress are exaggerated in these patients.

Oxidized Low-Density Lipoprotein (ox-LDL) to LDL Ratio (ox-LDL/LDL) and ox-LDL to High-Density Lipoprotein Ratio (ox-LDL/HDL):

BACKGROUND Oxidized low-density lipoprotein (ox-LDL) plays a principal role in diabetes complications, though ox-LDL concentrations and its functions are dependents of other oxidative and anti-oxidative particles. The oxLDL to low-density lipoprotein ratio (ox-LDL/LDL) and ox-LDL to high-density lipoprotein ratio (ox-LDL/HDL) as new lipid biomarkers may serve as a good estimation of oxidation and anti-oxidation in type 2 diabetes mellitus. The aim of this study was first to examine ox-LDL/LDL and ox-LDL/HDL levels in patients with type 2 diabetes mellitus compared to a control group and evaluate their diagnostic accuracies, and, second, to investigate the correlation of these two ratios with triglyceride and HDL levels. METHODS This study was included 144 patients admitted to the diabetes clinic of a University general hospital and 41 healthy individuals as controls. Levels of LDL, HDL, triglyceride (TG) ox-LDL, and malondialdehyde (MDA) were measured for all patients. Levels of ox-LDL/LDL and ox-LDL/HDL were calculated. Diagnostic accuracies were determined by receiver-operating characteristic curve analysis by measuring the area under the curve. RESULTS Ox-LDL, ox-LDL/LDL, and ox-LDL/HDL were significantly higher in patients compared to the control group after adjustment for age, gender, and BMI (p = 0.000). The area under the curve for diagnosing diabetes was 0.946 for ox-LDL/HDL, 0.918 for ox-LDL/LDL, and 0.832 for ox-LDL. Ox-LDL/HDL was positively correlated with MDA (r = 0.210, p = 0.011). Ox-LDL/LDL was negatively correlated with HDL (r = -0.2 p = 0.016) and positively correlated with TG (r = 0.45 p = 0.000). Ox-LDL/HDL and TG had significant positive correlation (r = 0.173 p = 0.037). The ox-LDL/LDL level was significantly higher in patients with coronary heart disease (CHD) or hypertension (HTN) compared to those without (p = 0.042). CONCLUSIONS Our findings revealed that ox-LDL/LDL and ox-LDL/HDL are potent biomarkers of type 2 diabetes, which apparently reflect the association between lipids in the state of oxidative stress.

Comparative effects of add-on pentoxifylline to losartan versus augmented dose losartan monotherapy on serum N-terminal pro-brain natriuretic peptide, serum highly sensitive C-reactive protein, and urinary albumin excretion rate in type 2 diabetes patients with nephropathy

Background: This study was designed to comparatively assess the effects of add‐on pentoxifylline to losartan versus increasing the dose of losartan on serum N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), serum highly sensitive C‐reactive protein (hsCRP) and the urinary albumin excretion (UAE) rate in patients with type 2 diabetes and nephropathy. Methods: In an open‐label, single‐center, parallel‐group, randomized clinical trial (NCT03006952), 30 patients received b.i.d. dose of pentoxifylline 400 mg plus daily dose of losartan 50 mg (pentoxifylline arm) and 29 patients received b.i.d. dose of losartan 50 mg (losartan arm) during a 12‐week follow‐up period. Results: Serum NT‐proBNP, serum hsCRP and UAE levels all significantly decreased from baseline in both trial arms. The pentoxifylline and losartan trial arms were equally effective in reducing serum NT‐proBNP levels during the course of trial (multivariable adjusted model P value = 0.864, effect size = 0.2%). There was a greater decrease in UAE and serum hsCRP levels in the pentoxifylline arm (P = 0.034, effect size = 7.8%; P = 0.009, effect size = 11.7%, respectively). Conversely, patients in the losartan arm achieved better systolic and diastolic blood pressure control (P < 0.001, effect size = 25.4%; P = 0.010, effect size = 11.3%, respectively). Conclusions: Circulating NT‐proBNP levels equally and significantly reduced from baseline in the pentoxifylline and losartan treatment arms, in parallel with comparatively superior decreases of UAE and serum hsCRP in the pentoxifylline arm, and larger decreases of systolic and diastolic blood pressures in the losartan arm.

National Prevalence of Self-Reported Coronary Heart Disease and Chronic Stable Angina Pectoris: Factor Analysis of the Underlying Cardiometabolic Risk Factors in the SuRFNCD-2011

BACKGROUND Coronary heart disease (CHD) is one of the most common causes of mortality worldwide. The national prevalence remains unclear in most of the developing countries. OBJECTIVE This study sought to estimate national prevalence of self-reported CHD and chronic stable angina pectoris in the general adult population of Iran using data from the fourth round of the Surveillance of Risk Factors of Non-Communicable Diseases (SuRFNCD-2011) survey. METHODS The analysis comprised data of 11,867 civilian, nonhospitalized and noninstitutionalized residents ages 6 to 70 years of age. The calculated prevalence of self-reported CHD and chronic stable angina pectoris were extrapolated to the Iranian adult population who were >20 years old using the complex sample analysis. The factor analysis was performed for clustering of the associated cardiometabolic risk factors among people ages >40 years of age. RESULTS The estimated national prevalence of self-reported CHD and chronic stable angina pectoris were 5.3% (95% confidence interval: 4.6 to 5.9) and 7.7% (95% confidence interval: 4.6 to 8.7), respectively. Higher prevalence of these conditions were observed among the older people, urban residents, and women. Factor analysis generated 4 distinct factors that were mainly indicators of dyslipidemia, hypertension, central obesity, hyperglycemia, and tobacco smoking. The factor incorporating hypertension was a significant correlate of self-reported CHD. CONCLUSIONS We report concerning prevalence of self-reported CHD and chronic stable angina pectoris in the adult population of Iran. The constellation of raised systolic and diastolic blood pressures was significantly predictive of the presence of self-reported CHD.