MRI of the arterial wall in resistant hypertension associated with type 2 diabetes mellitus

BACKGROUND: Damage of arterial walls in diabetes mellitus associated with arterial hypertension is major factor delivering lesion of target organs. Currently, enough data is not available about imaging and quantitative evaluations of arterial wall. There is no enough data available about the relations between MRI and inflammatory and metabolic markers in patients with resistant arterial hypertension concomitant with diabetes mellitus. AIMS: Quantitative assessment of the intensity of paramagnetic contrast enhancement of the arterial wall, in particular renal arteries walls, in relation with inflammatory and metabolic markers in patients with resistant arterial hypertension concomitant with diabetes mellitus. MATERIALS AND METHODS: The study groups were comprised of 28 patients (ageing 60,7±6,5 years) with resistant hypertension accompanied with diabetes mellitus and 17 patients (aging 57,7±5,0 years) with resistant hypertension without diabetes mellitus. The average systolic/diastolic pressure obtained from a 24-h monitor study was as high as 156,8±16,9/81,9,0±13,5 mm Hg in the group with diabetes and 154,8±11,9/88,5±10,4 mm Hg in the group without diabetes. The values of glycaemia, the level of glycated haemoglobin, and C-reactive protein were determined. The MRI studies were carried out using 1,5 Т MRI Toshiba Vantage Titan scanner. After that, the intravenous contrast enhancement has been carried out (with 0,5 М paramagnetic, as 0,2 ml/Kg). The index of enhancement (IE) was then calculated from these data, as a ratio of intensities of contrast-enhanced image to the initial nonenhanced MRI scan. RESULTS: The correlation was obtained for IE of arterial wall and data of blood pressure. Increased IE was correlated with ageing and hemodynamic factors. Also the correlation was observed for IE proximal, medium and distal parts of renal arteries and values of glycaemia and NOMA-index were obtained. Negatively correlated values for IE and adiponectin in the group with diabetes mellitus were obtained. The association between IE and C-reactive protein remained significant in the group without diabetes mellitus. CONCLUSIONS: MRI with contrast enhancement of arterial walls allows evaluating the anatomy of renal arteries and allows quantifying the pathophysiologic factors of their walls in patients with resistant hypertension accompanied with diabetes mellitus. MRI characteristics of the arterial wall were associated not only with hemodynamic and metabolic data, but also with markers of inflammation

Favorable effect of renal denervation on elevated renal vascular resistance in patients with resistant hypertension and type 2 diabetes mellitus

ObjectiveTo assess the effect of renal denervation (RDN) on renal vascular resistance and renal function in patients with drug-resistant hypertension (HTN) and type 2 diabetes mellitus (T2DM).Materials and methodsFifty-nine patients (mean age 60.3 ± 7.9 years, 25 men) with resistant HTN [mean 24-h ambulatory blood pressure (BP) 158.0 ± 16.3/82.5 ± 12.7 mmHg, systolic/diastolic] and T2DM (mean HbA1c 7.5 ± 1.5%) were included in the single-arm prospective study and underwent RDN. Renal resistive index (RRI) derived from ultrasound Doppler; estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration formula), office and 24-h ambulatory BP were measured at baseline, 6, and 12 months after RDN to evaluate the respective changes in renal vascular resistance, renal function, and BP during treatment.ResultsForty-three patients completed 12 months follow-up. The RRI changed depending on the baseline value. Specifically, the RRI decreased significantly in patients with elevated baseline RRI values ≥ 0.7 {n = 23; −0.024 [95% confidence interval (CI): −0.046, −0.002], p = 0.035} and did not change in those with baseline RRI < 0.7 [n = 36; 0.024 (95% CI: −0.002, 0.050), p = 0.069]. No significant change was observed in eGFR whereas BP was significantly reduced at 12 months after RDN by −10.9 (95% CI: −16.7, −5.0)/−5.5 (95% CI: −8.7, −2.4) mmHg, systolic/diastolic. No relationship was found between the changes in RRI and BP.ConclusionOur study shows that RDN can decrease elevated renal vascular resistance (RRI > 0.7) and stabilize kidney function in patients with RHTN and T2DM independently of its BP-lowering effect

Features of heart failure with preserved ejection fraction (HFpEF) in diabetic patients with resistant hypertension

BACKGROUND: It is expected that a steady increase in the incidence of diabetes and resistant hypertension (RHTN), along with an increase in life expectancy, will lead to a noticeable increase in the proportion of patients with heart failure with preserved ejection fraction (HFpEF). At the same time, data on the frequency of HFpEF in a selective group of patients with RHTN in combination with diabetes are still lacking, and the pathophysiological and molecular mechanisms of its formation have not been yet studied sufficiently.AIM: To assess the features of the development HFpEF in diabetic and non-diabetic patients with RHTN, as well as to determine the factors associated with HFpEF.MATERIALS AND METHODS: In the study were included 36 patients with RHTN and type 2 diabetes mellitus (DM) (mean age 61.4 ± 6.4 years, 14 men) and 33 patients with RHTN without diabetes, matched by sex, age and level of systolic blood pressure (BP). All patients underwent baseline office and 24-hour BP measurement, echocardiography with assess diastolic function, lab tests (basal glycemia, HbA1c, creatinine, aldosterone, TNF-alpha, hsCRP, brain naturetic peptide, metalloproteinases of types 2, 9 (MMP-2, MMP-9) and tissue inhibitor of MMP type 1 (TIMP-1)). HFpEF was diagnosed according to the 2019 AHA/ESC guidelines.RESULTS: The frequency of HFpEF was significantly higher in patients with RHTN with DM than those without DM (89% and 70%, respectively, p=0.045). This difference was due to a higher frequency of such major functional criterion of HFpEF as E/e’≥15 (p=0.042), as well as a tendency towards a higher frequency of an increase in left atrial volumes (p=0.081) and an increase in BNP (p=0.110). Despite the comparable frequency of diastolic dysfunction in patients with and without diabetes (100% and 97%, respectively), disturbance of the transmitral blood flow in patients with DM were more pronounced than in those without diabetes. Deterioration of transmitral blood flow and pseudo-normalization of diastolic function in diabetic patients with RHTN have relationship not only with signs of carbohydrate metabolism disturbance, but also with level of pulse blood pressure, TNF-alfa, TIMP-1 and TIMP-1 / MMP-2 ratio, which, along with the incidence of atherosclerosis, were higher in patients with DM than in those without diabetes.CONCLUSIONS: Thus, HFpEF occurs in the majority of diabetic patients with RHTN. The frequency of HFpEF in patients with DN is significantly higher than in patients without it, which is associated with more pronounced impairments of diastolic function. The progressive development of diastolic dysfunction in patients with diabetes mellitus is associated not only with metabolic disorders, but also with increased activity of chronic subclinical inflammation, profibrotic state and high severity of vascular changes

Cerebrovascular disorders in patients with type 2 diabetes mellitus and resistant hypertension

BACKGROUND: Diabetes mellitus (DM) and hypertension are risk factors for cerebral stroke, which are exacerbated by the combination of these diseases. Identifying the factors involved in the development of subclinical brain damage could change the therapeutic strategy for protecting the brain.AIM: to study severity of MRI- sings of brain damage and to identify factors associated with their development in patients with type 2 diabetes and RHTN.MATERIALS AND METHODS: 46 patients with type 2 DM and RHTN were included in a single-center observational uncontrolled study. Patients underwent brain MRI (1.5 Tesla) with calculation of Evans’s index (EI), clinical and lab examinations (HbA1c, glucose, insulin, C-peptide, leptin, resistin, TNF- α, hsCRP, blood aldosterone, insulin-like growth factor-1 (IGF-1)), measurement of the office and ambulatory blood pressure (BP), assessment of peripheral and cerebral vasoreactivity (test with hyperventilation and breath holding).RESULTS: The most frequent MR brain changes were white matter lesions (WML) in periventricular region (PVR) (89%), focal WML (52%) and expansion both of the ventricles (45%) and subarachnoid spaces (65%). Multiple direct correlations were revealed between parameters of carbohydrate metabolism with the degree of WML in PVR and the density of the MR-signal in the basal nucleus (BN), as well as with EI. Adipokines had a direct relationship with the size of the chiasmatic cistern and IE (for resistin), as well as with the density of the MR signal from the BN and IE (for leptin), that was also directly related to the IGF-1 level. The aldosterone level positively correlated with the size of III ventricle. An increase in TNF-α and hsCRP was accompanied by an increase in the density of the MR-signal in the PVR. Impairment of cerebrovascular reactivity is associated with an increase in the density of the MR-signal in PVR and with indirect signs of cerebral atrophy (increase in EI, the size of cisterns and lateral ventricles). Impairment of peripheral vasoreactivity had direct relationship with EI and the expansion of the III ventricle. There were no direct correlations between the severity of MR-sings of brain damage and BP levels.CONCLUSION: The combination of type 2 DM with RHTN is characterized by a high frequency of WML and liquorodynamics disturbances, which related with metabolic, neurohormonal and hemodynamic factors in the absence of a direct relationship with the degree of BP increas

МРТ сосудистой стенки с парамагнитным контрастным усилением в оценке терапевтического воздействия радиочастотной абляции симпатических сплетений почечных артерий при лечении резистентной артериальной гипертонии

Aim. Quantitative follow-up of the intensity of paramagnetic contrast enhancement of the aortal wall and renal arteries walls, as indicator of the pathological subinitimal and media neoangiogenesis was carried out in patients with arterial hypertension, focusing on changes after renal denervation.Material and methods. 31 patients (as old as 57.3 ± 9.8 years) with resistant hypertension comprised the study group. The average systolic/diastolic pressure obtained from 24-h monitor study was as high as 154 ± 12 / 89 ± 9 mm Hg. The MRI studies were carried out using 1.5 Т MRI Toshiba Vantage Titan scanner. After this the intravenous contrast enhancement has been carried out (with 0.5 М paramagnetic, as 0.2 ml/Kg). The radiofrequency ablation (RFA) desympathising the kidneys was performed on X-ray operating room using the Symplicity system: Symplicity Flex renal ablation electrode with a 4F end electrode as thin as 1.33 mm and with length of 1.5 mm, and also automated RF voltage generator with built-in power management algorithms temperature (Medtronic, USA) were employed. The comparison group included 28 people who were referred for MRI study of lumbar spine (average age - 53.2 ± 17.8), without any evidence that could be attributed to the pathology of the cardiovascular system.Results. Enhancement index (EI) of the aortic wall of patients with hypertension (1.57) was significantly over the aortic EI of healthy people (1.23), p < 0.0001, reflecting inflammatory neoangiogenetic changes in the vascular wall in hypertension. The correlation between EI in the wall of both renal arteries is highly reliable and linear, which confirms the idea of the systemic nature of neoangiogenesis in hypertension. Analysis of data from an MRI study of the renal arteries showed that the intensity of the accumulation of the contrast agent in their wall after RD, as a rule, decreases (the right RA distal segment 1.78, 1.61, 1.59 - at baseline, at 6 and 12 months after RD, respectively (p < 0.05). Thus, a visual MRI proves electro-induced damage to the wall of the renal artery and the development of fibrosis at the site of radiofrequency exposure. At the same time, there are no significant differences in EI between studies at the sixth (p = 0.56) and twelfth (p = 0.48) months of observation after RFA, which argues in favor of maintaining fibrosis and, respectively, the absence of reinnervation and inflammatory neoangiogenesis of the arterial wall.Conclusion. MR-tomographic examination of the aorta and renal arteries with contrast enhancement should be carried out to assess the state of the walls of these vessels and to dynamically monitor their condition after renal denervation.Цель исследования: количественная оценка интенсивности контрастного усиления стенки аорты и почечных артерий как показателя протекающего патологического неоангиогенеза у пациентов с артериальной гипертонией (АГ) с оценкой его изменений после ренальной денервации.Материал и методы. Обследован 31 пациент с резистентной АГ, средний возраст 57,3 ± 9,8 года. СМАД 154 ± 12 / 89 ± 9 мм рт.ст. МРТ-исследование проводилось на МР-томографе 1,5 Тл. Протокол включал стандартные режимы для исследования сердца и грудной аорты. Контрастное усиление: внутривенно медленно 0,5 М парамагнитного контрастного препарата (0,2 мл/кг массы тела). Ренальная симпатическая денервация выполнялась в рентгеноперационных с использованием лицензированного оборудования системы Symplicity (Medtronic, США). Группа сравнения - 28 человек, проходивших амбулаторно МРТ поясничного отдела позвоночника (средний возраст 53,2 ± 17,8 года), без жалоб, которые можно было бы отнести к патологии сердечно-сосудистой системы.Результаты. Индекс усиления (ИУ) стенки аорты больных с АГ (1,57) достоверно отличается от ИУ аорты здоровых людей (1,23), p < 0,0001, что отражает воспалительно-неоангиогенетические изменения в сосудистой стенке при АГ. Корреляция между показателями ИУ стенки почечных артерий высокодостоверна и линейна, что подтверждает представление о системном характере неоангиогенеза при АГ. В результате анализа данных, полученных при МРТ почечных артерий, оказалось, что при контрастировании интенсивность МРТ-сигнала от их стенок, как правило, уменьшается (правая почечная артерия дистальный сегмент 1,78, 1,61, 1,59 - исходно, в 6 и 12 мес после ренальной денервации соответственно, p < 0,05). Таким образом, визуально МРТ доказывает электроиндуцированное повреждение стенки почечной артерии и развитие фиброза в месте радиочастотного воздействия. При этом нет достоверных различий в ИУ между исследованиями на 6-м (р = 0,56) и 12-м (р = 0,48) месяце наблюдения после РЧА, что свидетельствует в пользу сохранения фиброза и соответственно отсутствия реиннервации и воспалительного неоангиогенеза артериальной стенки.Заключение. МРТ-исследование аорты и почечных артерий с контрастным усилением рекомендуется проводить как диагностическую процедуру, позволяющую оценить состояние стенки данных сосудов, а также для динамического наблюдения за их состоянием после ренальной симпатической денервации

ДИНАМИКА СОСТОЯНИЯ УГЛЕВОДНОГО ОБМЕНА ПОСЛЕ РЕНАЛЬНОЙ ДЕНЕРВАЦИИ У БОЛЬНЫХ РЕЗИСТЕНТНОЙ АРТЕРИАЛЬНОЙ ГИПЕРТОНИЕЙ В СОЧЕТАНИИ С САХАРНЫМ ДИАБЕТОМ 2-ГО ТИПА

The aim of the study was to evaluatetheglycemic control dynamics depending on degree of blood pressure (BP) reduction and dynamic of TNF-α after 6 and 12 months of Tran catheter renal denervation (TRD) of patients with true resistant hypertension (RH) and type 2 diabetes mellitus (T2DM). Material and methods. Thirty two essentially hypertensive patients with type 2 diabetes mellitus (T2DM) and resistant hypertension were included in single-arm prospective interventional study. Office BP measurement, ambulatory 24-h BP, renal Doppler ultrasound and assessment of renal function (proteinuria, creatinine, eGFR), HbА1c and fasting plasma glucose (FPG) levels, activity of TNF-α were performed at baseline and 6 and 12 months after TRD. On average, patients were taking 4 (3–6) antihypertensive drugs. None of the patients changed the antihypertensive treatments during follow-up. A 6 months follow-up was completed by 27 patients (43–75 years old, 14 male), 12 months follow-up was completed by 26 patients. Results. Renal denervation significantly reduced the systolic office BP (SBP) as well as 24-h SBP (– 27.2/–10.7 mm Hg and–13.4/–10 mm Hg, respectively, p < 0.01 after 6-month follow-up, and –31,7/–12,8 mmHg and –13.4/–10 mm Hg, respectively, p < 0.01 after 12-month follow-up) without any negative effect on renal function. The number of responders with reduction of SBP >10 mmHg according to ABPM were 56% (15/27) after 6-month and 61.5% (16/26) after 12-month follow-up. There were significant reduction of the average HbA1c levels (from (6.9 ± 1.8)% to (5.8 ± 1.5)%, p = 0.04) and nonsignificant decreasing of FPG levels (from 8.7 ± 2.8 to 7.7 ± 2.1 mmol/L, p = 0.07) after 6-month followup. Conspicuously, the responders according to ABPM had significantly higher mean dynamics of HbA1c than the non-responders after 6-month follow-up (–2.4 ± 1.9 and –0.1 ± 0.8%, p = 0.02, respectively) as well as after 12-month follow-up (–0.12 ± 0.98 and 1,26 ± 1.11%, p = 0.04 for HbA1c, and – 0.89 ± 1.9 и 0.85 mmol/L ± 1.19, p = 0.02 for FPG levels). There were significant decreasing of TNF-α after 12-monthfollow-up (from 2.21 (1.54–3.65) to 1.4 (1.11–1.47pg/ml), p = 0.007), without relation to BP and HbA1c dynamics, and response to TRD. There were not the correlations between dynamics of HbA1c and FPG levels with BP reduction and change of TNF-α after 12-month follow-up. Conclusions. Renal denervation of patients with true resistant hypertension and diabetes mellitus type 2 after 6 and 12 months was followed by improved glycemic control, BP reduction and decreasing of mean levels of TNF-α. Glycemic control improvement after the renal denervation was more expressive in the responders. Цель исследования – оценить изменение состояния углеводного обмена через 6 мес и 1 год после ренальной денервации (РД) в зависимости от степени антигипертензивного эффекта и динамики фактора некроза опухолей α (ФНО-α) у больных резистентной артериальной гипертонией (РАГ) в сочетании с сахарным диабетом (СД) 2-го типа (СД-2).Материал и методы. Ренальная денервация почечных артерий проведена у 32 больных истинно резистентной АГ в сочетании с СД-2. Полугодовой период наблюдения закончили 27 пациентов (14 мужчин и 13 женщин (возраст 43–75 лет)), годовое наблюдение – 26 человек. Всем больным проводили общеклиническое обследование, измерение офисного артериального давления (АД), 24-часовое амбулаторное мониторирование АД (АМАД), допплерографию почечных артерий, оценивали состояние углеводного обмена (базальная гликемия, гликированный гемоглобин (HbA1c), концентрацию в плазме крови ФНО-α и почечную функцию (протеинурия, креатинин сыворотки крови, расчетная скорость клубочковой фильтрации (по формуле MDRD). Пациенты получали в среднем 4 (3–6) антигипертензивных препарата. Антигипертензивная и сахароснижающая терапия оставались стабильными в течение всего периода наблюдения. Результаты. Через 6 мес после РД отмечался значимый антигипертензивный эффект (–27,2/–10,7 мм рт. ст. для офисного АД и –13,4/–10,0 мм рт. ст. для АД–24-ч, p < 0,01), остававшийся стабильным в течение всего года (–31,7/–12,8 мм рт. ст. и –13,4/–10,0 мм рт. ст., соответственно,p < 0,01). Снижение систолического АД (САД) более 10 мм рт. ст от исходных значений (группа респондеров) по результатам АМАД через 6 мес зарегистрировано у 56% больных (15 из 27 пациентов), через год – 61,5% (16 из 26 человек). Через 6 мес после вмешательства установлено статистически значимое уменьшение среднего уровня HbA1c (от (6,9 ± 1,8) до (5,8 ± 1,5)%, p = 0,04) и тенденция к снижению базальной гликемии (от 8,7 ± 2,8 до (7,7 ± 2,1) ммоль/л, p = 0,07). При этом снижение HbA1c было более выраженным у респондеров (по САД–24 ч), чем у нереспондеров  (–2,4 ± 1,9 и –0,1 ± 0,8 соответственно, p = 0,02). Различие динамики HbA1c между респондерами и нереспондерами cохранялось и через год наблюдения (–0,1 ± 1,0 и 1,3 ± 1,1, p = 0,04), также как и динамики базальной гликемии (–0,9 ± 1,9 и 0,8 ± 1,2, p = 0,02). Через год после РД было обнаружено статистически значимое снижение уровня ФНО-α (от 2,21 (1,54–3,65) до 1,40 (1,11–1,47) пг/мл),p = 0,007), не зависящее от выраженности снижения АД и ответа на вмешательства. Прямой связи между снижением показателей углеводного обмена и динамикой концентрации ФНО-α, а также степенью антигипертензивного эффекта через год также не отмечено. Выводы. Ренальная денервация у больных резистентной АГ, ассоциированной с СД-2, оказывала благоприятное влияние на состояние углеводного обмена на фоне выраженного и стабильного в течение года антигипертензивного эффекта, а также снижения активности ФНО-α. При этом статистически значимое улучшение гликемического контроля отмечалось при снижении среднесуточного систолического АД более 10 мм рт. ст. от исходных значений