SAT-612 Features of the Severity of Cardiovascular Remodeling and Metabolic Disorders in Hypertensive Patients with Obesity in the Presence of Two Unfavorable Genotypes of the ADIPOQ and IRS-1 Genes

Abstract The results of a number of studies have shown that in arterial hypertension (AH), G/T and T/T genotypes of the adiponectin gene (ADIPOQ) and Gly/Arg and Arg/Arg genotypes of the insulin receptor substrate 1 gene (IRS-1) are associated with a greater severity of metabolic disorders and hemodynamic parameters compared with G/G and Gly/Gly genotypes of these genes. The aim of the study: to evaluate the severity of cardiovascular remodeling and metabolic disorders in hypertensive obese patients in the simultaneous presence of two unfavorable genotypes of the ADIPOQ and IRS-1 genes. Methods: We examined 300 AH patients: 200 patients with AH and obesity, 50 patients with AH and normal body weight, 50 patients with AH and overweight, 40 patients with AH, obesity and type 2 diabetes mellitus (DM2), 30 healthy individuals. The polymorphisms of the ADIPOQ and IRS-1 was assessed by molecular genetic method. Results: It was found that in all groups of hypertensive patients, regardless of body weight and the presence of DM2, the simultaneous presence of two unfavorable genotypes of the ADIPOQ and IRS-1 genes occurred significantly more often than in healthy individuals: in 41% of AH patients with obesity, 30% of AH patients with normal weight, 40% of AH with overweight, 57.5% of AH with obesity and DM2 vs. 13.3% of healthy individuals. In hypertensive patients, in the presence of overweight and obesity, the frequency of combination of the two unfavorable genotypes of these genes was significantly higher than in AH patients with normal body weight. Conducting comparative evaluation of AH patients with obesity depending on the presence of two unfavorable genotypes or two protective genotypes of the ADIPOQ and IRS-1 genes showed that carriers of the combination of the G/T + T/T genotype of the ADIPOQ and the Gly/Arg + Arg/Arg genotype of the IRS-1 had a higher body mass index, more pronounced insulin resistance, cardiovascular remodeling, adipokine imbalance, impaired carbohydrate and lipid metabolism. Conclusions: In AH patients, the frequency of the simultaneous presence of two unfavorable polymorphisms of ADIPOQ and IRS-1 genes was higher than in healthy individuals. In AH patients with overweight and obesity, the frequency of combination of the two unfavorable genotypes of the ADIPOQ and IRS-1 genes was significantly higher than in normal body weight. The presence of a combination of two unfavorable genotypes of the ADIPOQ and IRS-1 genes in patients with AH and obesity was associated with a greater severity of cardiovascular remodeling and metabolic disorders compared with the combination of two protective genotypes of these genes.


MON-221
Abstract: Objective: Saline suppression testing (SST) and captopril challenge test (CCT) are commonly used confirmatory tests for primary aldosteronism (PA). Seated SST (SSST) is reported to be superior to recumbent SST (RSST). Whether SSST is better than CCT remains unclear. Therefore we conducted a prospective study to compare the diagnostic accuracy of SSST and CCT. Methods: Hypertensive patients with high risk of PA were consecutively included. Patients with aldosterone-renin ratio≥1.0 ng•dl-1/μIU•ml-1 were asked to complete SSST, CCT and fludrocortisone suppression test (FST). Using FST as the reference standard (plasma aldosterone concentration [PAC] post-FST ≥6.0 ng•dl-1), area under the receiver-operator characteristic curves (AUC), sensitivity and specificity of SSST and CCT were calculated, and multiple regression analyses were conducted to identify potential factors for false diagnosis. Results: A total of 183 patients diagnosed as PA and 48 as essential hypertension completed the study. Using PAC post-SSST and PAC post-CCT to confirm PA, SSST and CCT had comparable AUCs (AUCSSST 0.83 [0.78,0.88] vs. AUCCCT 0.86 [0.81,0.90], P=0.308). Setting PAC post-SSST and post-CCT at 8.5 ng•dl-1 and 11 ng•dl-1, respectively, the sensitivity and specificity of SSST [0.71 (95%CI 0.64 to 0.77) and 0.82(0.68,0.90)] and CCT [0.73(0.66,0.79) and 0.80(0.66,0.89)] were not significantly different. In the multiple regression analyses, 1SD increment of sodium intake resulted in 40% lower risk of false diagnosis in SSST. Conclusions: SSST and CCT have comparable diagnostic accuracy. Insufficient sodium intake decreases the diagnostic efficiency of SSST but not CCT. Since the CCT is simpler and cheaper, it is preferable to the SSST.

Features of the Severity of Cardiovascular Remodeling and Metabolic Disorders in Hypertensive Patients with Obesity in the Presence of Two Unfavorable Genotypes of the ADIPOQ and IRS-1 Genes
Anna Shalimova, MD, PhD 1 , Valentyna Psarova, MD, PhD 2 , Nataliia Kyrychenko, MD, PhD 2 , Maryna Kochuieva, MD, PhD 3 . 1 L.T. Malaya Therapy National Institute of the NAMS of Ukraine', Kharkiv, Ukraine, 2 Sumy State University, Sumy, Ukraine, 3 Kharkiv Medical Academy of Postgraduate Education, Kharkiv, Ukraine.

SAT-612
The results of a number of studies have shown that in arterial hypertension (AH), G/T and T/T genotypes of the adiponectin gene (ADIPOQ) and Gly/Arg and Arg/Arg genotypes of the insulin receptor substrate 1 gene (IRS-1) are associated with a greater severity of metabolic disorders and hemodynamic parameters compared with G/G and Gly/ Gly genotypes of these genes. The aim of the study: to evaluate the severity of cardiovascular remodeling and metabolic disorders in hypertensive obese patients in the simultaneous presence of two unfavorable genotypes of the ADIPOQ and IRS-1 genes. Methods: We examined 300 AH patients: 200 patients with AH and obesity, 50 patients with AH and normal body weight, 50 patients with AH and overweight, 40 patients with AH, obesity and type 2 diabetes mellitus (DM2), 30 healthy individuals. The polymorphisms of the ADIPOQ and IRS-1 was assessed by molecular genetic method. Results: It was found that in all groups of hypertensive patients, regardless of body weight and the presence of DM2, the simultaneous presence of two unfavorable genotypes of the ADIPOQ and IRS-1 genes occurred significantly more often than in healthy individuals: in 41% of AH patients with obesity, 30% of AH patients with normal weight, 40% of AH with overweight, 57.5% of AH with obesity and DM2 vs. 13.3% of healthy individuals. In hypertensive patients, in the presence of overweight and obesity, the frequency of combination of the two unfavorable genotypes of these genes was significantly higher than in AH patients with normal body weight. Conducting comparative evaluation of AH patients with obesity depending on the presence of two unfavorable genotypes or two protective genotypes of the ADIPOQ and IRS-1 genes showed that carriers of the combination of the G/T + T/T genotype of the ADIPOQ and the Gly/Arg + Arg/Arg genotype of the IRS-1 had a higher body mass index, more pronounced insulin resistance, cardiovascular remodeling, adipokine imbalance, impaired carbohydrate and lipid metabolism. Conclusions: In AH patients, the frequency of the simultaneous presence of two unfavorable polymorphisms of ADIPOQ and IRS-1 genes was higher than in healthy individuals. In AH patients with overweight and obesity, the frequency of combination of the two unfavorable genotypes of the ADIPOQ and IRS-1 genes was significantly higher than in normal body weight. The presence of a combination of two unfavorable genotypes of the ADIPOQ and IRS-1 genes in patients with AH and obesity was associated with a greater severity of cardiovascular remodeling and metabolic disorders compared with the combination of two protective genotypes of these genes.

OR30-06
Background: Dulaglutide (DU) was superior to placebo (PL) in reducing the incidence of Major Adverse Cardiovascular Events in the Researching Cardiovascular Events with a Weekly INcretin in Diabetes (REWIND Study) broad patient population. The safety of DU treatment is also of interest to health care providers who treat an older patient population (≥65 years of age). Aims: The primary objective of this post-hoc analysis was to evaluate DU safety in the REWIND patient subgroup populations categorized by age (≥ 65 and < 65 years) with regards to the occurrence of the composite safety outcome of overall mortality and severe hypoglycemia. One of the key secondary objectives was first occurrence of severe hypoglycemia. Methods: Patients were grouped into two age groups: ≥65 and <65 years. Time-to-event for the composite safety endpoint as well as individual variables were analyzed using Cox proportional hazards regression. Hazard ratios (HRs) and 95% confidence intervals (CIs) for between group treatment differences were also calculated. Results: Of the 9,901 patients randomized in REWIND, a total of 5,256 (DU, 2,619; PL, 2,637) were aged ≥65 years. The incidence of the composite safety outcome for patients aged ≥65 years was 399 of 2619 (15.2%) for DU-treated patients and 425 of 2,637 (16.1%) for PL-treated patients. The incidence of the composite safety outcome for those aged <65 years was 188 of 2,330 (8.1%) for DU-treated patients and 224 of 2,315 (9.7%) for PL-treated patients. Between group treatment differences (HR [95% CI]) were 0.94 (0.82, 1.08) for patients ≥65 years of age and 0.82 (0.68, 1.00) for patients <65 years of age; interaction p-value = 0.277. The incidence of the secondary outcome of first occurrence of severe hypoglycemia for patients aged ≥65 years was 46 of 2619 (1.8%) for DU-treated patients and 49 of 2,637 (1.9%) for PL-treated patients. The incidence of this outcome for patients <65 years was 18 of 2,330 (0.8%) for DU-treated patients and 25 of 2,315 (1.1%) for PL-treated patients. Between group treatment differences (HR [95% CI]) were 0.95 (0.63, 1.42) for patients ≥65 years of age and 0.71 (0.39, 1.31) for patients <65 years of age; interaction p-value = 0.443. The safety profile of DU was reviewed based upon the results of subgroup analysis of treatment emergent adverse events and serious adverse events by preferred terms for comparing PL and DU for age subgroups (≥65 years of age versus <65 years). None of the results indicated that DU has a different safety profile across the age subgroups evaluated in this post-hoc analysis.
Conclusions: Treatment with DU demonstrated similar safety in REWIND patients aged ≥65 years and those aged <65 years. Dulaglutide can be considered a safe and effective treatment option for use in older adults.