ОЦІНКА СЕРЦЕВО-СУДИННОГО РИЗИКУ У ЧОЛОВІКІВ ІЗ ГІПЕРТОНІЧНОЮ ХВОРОБОЮ НА ТЛІ АНДРОГЕННОГО ДЕФІЦИТУ

Data from numerous studies show the correlation of low testosterone in men with certain CVD risk factors such as obesity, type 2 diabetes, metabolic syndrome. Statistical approaches include the calculation of cardiovascular risk for general population, and their use for risk assessment in men with testosterone deficiency is still not well-described in the literature.The aim of the study – to determine the most valid approach for assessment of cardiovascular risk in hypertensive men with androgen deficiency using the comparative analysis of Framingham, SCORE and PROCAM scales.Material and Methods. The study included 50 male patients with a diagnosis of stage II hypertension and 11 healthy subjects who were included into the control group. All participants were subjected to the general clinical examination, evaluation of lipid profile and total serum testosterone (TT), cardiovascular risk assessment using Framingham scale (FS), SCORE and PROCAM scales. Depending on the level of TT, the patients were divided into 2 groups: 1 group (n = 27) – with testosterone deficiency, 2 group (n = 23) with normal TT level.Results. Analysis of cardiovascular risk of the study participants showed that 55.6 % of men in group 1 and 43.5 % of group 2 had high cardiovascular risk according to FS, while PROCAM risk of over 20 % had 66.7 % and 39.1 % of patients respectively. 51.8 % of men in group 1 and 39.1 % of group 2 were in high risk cohort due to SCORE scale. There was no significant difference between the risk by FS and by SCORE between groups 1 and 2, while the difference between these groups was statistically significant when PROCAM scale was used. Negative correlation was found between cardiovascular risk and TT level, with a statistically significant correlation between TT and PROCAM (p <0.05).Conclusions. The use of the PROCAM scale is the most reasonable for categorizing of cardiovascular risk in cohort of hypertensive men associated with androgen deficiency. Введение. Данные многочисленных исследований указывают на связь низкого уровня тестосте- рона у мужчин с отдельными факторами риска ССЗ (ожирение, сахарный диабет 2 типа, метаболический синдром и т.п.). Статистические подходы предусматривают расчет кардиоваскулярного риска для общей популяции, а ис- пользование их для оценки риска у мужчин с дефицитом тестостерона в литературе не описано.Цель исследования – на основании сравнительного анализа ряда шкал (Фремингемской, SCORE и PROCAM) определить наиболее валидную для оценки сердечно-сосудистого риска у мужчин с гипертонической болезнью на фоне андрогенного дефицита.Материал и методы. Исследование включало 50 пациентов мужского пола с установленным диагнозом гипертонической болезни II стадии и 11 практически здоровых лиц, вошедших в контрольную группу. У всех участников исследования, наряду с общеклиническим обследованием, определяли параметры липидного профиля и общий тестостерон (ОТ) сыворотки крови, оценивали сердечно-сосудистый риск по Фремингемской шкале (ФШ), шкалам SCORE и PROCAM. В зависимости от уровня ОТ обследованные были поделены на 2 группы: 1 группа (n=27) – с дефицитом ОТ, 2 группа (n=23) с нормальным уровнем ОТ.Результаты. При анализе сердечно-сосудистого риска участников исследования установлено, что по ФШ к группе высокого риска принадлежали 55,6 % мужчин 1 группы и 43,5 % лиц 2 группы, по шкале PROCAM риск выше 20 % имели 66,7 % и 39,1 % пациентов соответственно. Доля обследованных, имевших высокий риск по шкале SCORE, составила 51,8 % среди мужчин 1 группы и 39,1 % – 2 группы. Значимых различий между риском по ФШ и SCORE между группами 1 и 2 обнаружено не было, в то время как разница между указанными группами быластатистическидостовернойпошкале PROCAM. Корреляционныйанализпоказалтенденциюкотрицательной обратной связи между сердечно-сосудистым риском и уровнем ОТ, при этом статистически значимой корреляция была только между ОТ и риском по шкале PROCAM (р<0,05).Выводы. Использование шкалы PROCAM является наиболее обоснованным для категоризации риска в когорте мужчин с гипертонической болезнью, ассоциированной с андрогенным дефицитом.Вступ. Дані численних досліджень вказують на зв’язок низького рівня тестостерону у чоловіків із окремими факторами ризику ССЗ (ожиріння, цукровий діабет 2 типу, метаболічний синдром тощо). Статистичні підходи передбачають розрахунок кардіоваскулярного ризику для загальної популяції, а використання їх для оцінки ризику у чоловіків із дефіцитом тестостерону в літературі не описане.Мета дослідження. На підставі порівняльного аналізу ряду шкал (Фремінгемська, SCORE та PROCAM ) визначити найбільш валідну для оцінки серцево-судинного ризику у чоловіків із гіпертонічною хворобою на тлі андрогенного дефіциту.Матеріал і методи дослідження. Дослідження включало 50 пацієнтів чоловічої статі із встановленим діагнозом гіпертонічної хвороби ІІ стадії та 11 практично здорових осіб, що увійшли до контрольної групи. Всім учасникам дослідження поряд із загальноклінічним обстеженням визначалися параметри ліпідного профілю та загальний тестостерон (ЗТ) сироватки крові, оцінювався серцево-судинний ризик за Фремінгемською шкалою (ФШ), шкалами SCORE та PROCAM. В залежності від рівня ЗТ обстежені були розподілені на 2 групи: 1 група (n=27) – з дефіцитом ЗТ, 2 група (n=23) з нормальним рівнем ЗТ.Результати досліджень. При аналізі серцево-судинного ризику учасників дослідження встановлено, що за ФШ до групи високого ризику  належали 55,6% чоловіків 1 групи та 43,5% осіб 2 групи, за шкалою PROCAM  ризик вище 20% мали 66,7% та 39,1% пацієнтів відповідно. Частка обстежених, що мали високий ризик за шкалою SCORE, склала 51,8% серед чоловіків 1 групи та 39,1% - 2 групи. Значущих відмінностей між  ризиком за ФШ та SCORE між групою 1 та 2 виявлено не було, в той час як різниця між вказаними групами була статистично вірогідною за шкалою PROCAM. Кореляційний аналіз продемонстрував тенденцію до негативного зворотного зв’язку між серцево-судинним ризиком та рівнем ЗТ, при цьому статистично значущою кореляція була лише між ЗТ та ризиком за шкалою PROCAM (р<0.05).Висновки. Використання шкали PROCAM є найбільш обґрунтованим для категоризації ризику у когорті чоловіків із гіпертонічною хворобою, асоційованою з андрогенним дефіцитом

Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: Subgroup analysis of the DISTINCT randomised trial

The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS - Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min-1, n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of bodysurface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2 ), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of endstage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years. (Funded by Janssen Research and Development; CREDENCE ClinicalTrials.gov number, NCT02065791.

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)