Comprehensive Assessment of Cardiohemodynamics and Catestatin Parameters as a Possible Predictor of Cardiovascular Dysfunction in Patients with Arterial Hypertension without and with Comorbid Type 2 Diabetes Mellitus and Obesity

Catestatin (CST) is a pleiotropic peptide with cardioprotective and metabolic effects. CST is involved in the pathogenesis of both arterial hypertension (AH) and type 2 diabetes mellitus (T2DM), which are the risk factors of cardiovascular diseases. In this study, we aimed to investigate the plasma CST levels in hypertensive patients, especially with T2DM, as well as compare those with healthy volunteers, and explore the relationship between CST levels and clinical, anthropometric and laboratory parameters. 106 Hypertensive patients, 55 of which had comorbidity T2DM, and 30 healthy volunteers were enrolled in the study. All subjects underwent clinical examination, including vital signs and anthropometric data assessment, medical history interview, and blood sample collection. Plasma CST levels were measured by an enzyme-linked immunosorbent assay (ELISA), using a commercial diagnostic kit. The plasma CST levels were significantly lower in hypertensive patients (N = 106) compared with healthy subjects (N = 30) (5.02 ± 1.09 vs. 6.64 ± 0.72; p < 0.001). Furthermore, hypertensive patients with T2DM (N = 55) have significantly reduced CST levels in comparison with those without T2DM (N = 51) (4.47 ± 1.16 vs. 5.61 ± 0.61; p < 0.001). CST significantly correlated with anthropometric characteristics, in particular, weight (r = -0.344; p < 0.001), BMI (r = -0.42; p < 0.001), neck (r = -0.358; p < 0.001), waist (r = -0.487; p < 0.001), hip (r = -0.312; p < 0.001), wrist circumferences (r = -0.264; p = 0.002), and waist-to-hip ratio (r = -0.395; p < 0.001). Due to its antihypertensive effect, CST has significant associations with systolic BP (r = -0.475; p < 0.001) and duration of AH (r = -0.26; p = 0.007). CST also has an inverse relationship with insulin (r = -0.382; p < 0.001), glucose (r = -0.45; p < 0.001), index HOMA-IR (r = -0.481; p < 0.001) and HbA1c (r = -0.525; p < 0.001), that indicate its involvement in T2DM development. Besides, CST has significant correlations with uric acid levels (r = -0.412; p < 0.001) as well as lipid parameters, especially HDL-C (r = 0.480; p < 0.001), VLDL-C (r = -0.238; p = 0.005), TG (r = -0.4; p < 0.001), non-HDL-C/HDL-C (r = -0.499; p < 0.001). Multiple linear regression analysis indicated BMI (β = -0.22; p = 0.007), AH duration (β = -0.25; p = 0.008), HbA1c (β = -0.43; p = 0.019) and HDL-C levels (β = 0.27; p = 0.001) as independent predictors of CST levels. The hypertensive patients have significantly decreased CST levels that are even more reduced in the presence of comorbid T2DM. The established correlations with anthropometric and laboratory parameters indicate not only antihypertensive but also metabolic effects of CST. Our results suggest the probable role of CST in the pathophysiology of cardiometabolic diseases and the development of cardiovascular complications.

Diabetes mellitus and heart failure: insights from a toxic relationship

Background. Hypertension is the major pandemic in human history, which determines the structure of cardiovascular morbidity and mortality. There is an obvious relationship between hypertension and various diseases that largely determine its development and increase the risk of cardiovascular complications. Neuropeptides appear to have a major impact on the progression of these complications. Catestatin (CST) is one of them, which deserves special scientific and practical concern, as it has a wide range of biological effects in the body. The aim of the study: to determine the place of CST in the early diagnosis of cardiovascular and metabolic complications in patients with comorbid hypertension among the Ukrainian population. Materials and methods. One hundred and eleven patients with hypertension, type 2 diabetes mellitus, obesity (men/women — 50/61) and 20 controls were examined. All patients with hypertension, type 2 diabetes mellitus, and obesity were aged 54.37 ± 1.18 years. Following a thorough examination and supervision, they were divi­ded into 2 groups depending on the median CST level of 2.45 ng/ml. The first group included 55 (49.5 %) patients who had a CST level below 2.45 ng/ml, the second one consisted of 56 patients (50.5 %) who had a CST level above 2.45 ng/ml. In all patients, we measured body weight, height, calculated body mass index, evaluated glycated hemoglobin levels, lipid metabolism (serum concentrations of total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and very low-density lipoprotein cholesterol); systolic and diastolic blood pressure. The content of CST, cardiotrophin 1, leptin, cystatin C, neutrophil gelatinase-associated lipocalin, N-terminal prohormone of brain natriuretic peptide, 25(OH)D, β2-microglobulin, and insulin levels in the blood serum were determined by enzyme-linked immunosorbent assay. Results. A reliable difference between the groups was found by β2-microglobulin (p = 0.008). Univariate and multivariate linear regression analysis revealed a negative correlation between CST and cardiotrophin 1, N-terminal prohormone of brain natriuretic peptide, neutrophil gelatinase-associated lipocalin, and 25(OH)D. A positive correlation was found between CST and the level of glycated hemoglobin, body mass index, and triglycerides. A statistically significant correlation was found between CST and creatinine (R = –0.21, p = 0.029), high-density lipoprotein cholesterol (R = 0.207, p = 0.029), and β2-microglobulin (R = 0.279, p = 0.0029) in the patients with hypertension. Conclusions. It has been proven that a decrease in serum catestatin concentration can be a risk factor for the development of more severe comorbidities in patients with hypertension. The detected relationships of catestatin with creatinine, urea, and β2-microglobulin suggest that CST is a predictor of chronic kidney disease in patients with comorbidities. The revealed correlation of CST with high-density lipoprotein, obesity, and body mass index suggests its importance in the prevention of atherosclerotic and metabolic complications in patients with hypertension, type 2 diabetes mellitus, and obesity.

Cardiometabolic phenotypes in patients with arterial hypertension (AH), type 2 diabetes mellitus (T2DM) and obesity (OB) are an important medical problem. Studying the impact of complex treatment on these phenotypes will contribute to improving therapeutic strategies. Objective — to establish features of changes in cardiometabolic phenotypes in patients with arterial hypertension, type 2 diabetes mellitus, and obesity in the dynamics of treatment. Materials and methods. The study included 211 patients with AH, who were divided into four groups depending on the presence of OB and T2DM. The levels of catestatin (CST), cardiotrophin‑1 (CTF‑1), β2‑microglobulin (β2‑M), N‑terminal polypeptide of natriuretic hormone (NT‑proBNP), lipocalin, associated with neutrophil gelatinase (NGAL), cystatin C, 25‑OH vitamin D, leptin, insulin, glycated hemoglobin and blood lipid spectrum were determined. An ultrasound examination of the heart was performed. Logistic regression and analysis of variance (ANOVA) methods were used. Results. It was found that complex treatment contributes to the reduction of cardiometabolic risk through the normalization of CST, CTF‑1 and β2‑M levels. In patients with hypertension, a decrease in CST is associated with the formation of a favorable phenotype, while in the group with АН and ОВ, its increase indicates the activation of compensatory mechanisms. In patients with АН and Т2DM, a positive effect was noted when insulin and leptin levels were reduced. Conclusions. Due to the comprehensive treatment of patients with arterial hypertension, type 2 diabetes mellitus and obesity, it is possible to achieve the formation of favorable cardiometabolic phenotypes to improve the prognosis.

Subclinical left ventricular (LV) dysfunction is prevalent in type 2 diabetes (T2DM). As obesity has been proposed as one causal factor in the disease process, this could bias the reported prevalences. We wanted to characterize echocardiographic LV dysfunction in obese T2DM subjects as compared to non-diabetic obese controls. One hundred patients with T2DM without clinical signs of heart failure (29% females, mean ± SD age 58.4 ± 10.5 years, body mass index (BMI) 30.1 ± 5.5 kg/m(2), blood pressure (BP) 141 ± 18/83 ± 9 mmHg) and 100 non-diabetic controls (29% females) matched for age (58.6 ± 10.5 years), BMI (29.8 ± 4.0 kg/m(2) and systolic BP (140 ± 14 mmHg) underwent echocardiography and color tissue Doppler imaging (TDI). Diastolic function was evaluated with conventional Doppler recordings and early (e') and late (a') myocardial velocities. The ratio between early transmitral filling (E) and the corresponding myocardial tissue velocity (e') served as an index of LV filling pressure. T2DM patients had more concentric hypertrophy with a relative wall thickness of 0.42 ± 0.07 vs controls 0.38 ± 0.07, P < 0.001. The T2DM group had signs of diastolic dysfunction with lower E/A ratio (0.91 ± 0.27 vs. 1.12 ± 0.38, P < 0.001), deceleration time (195 ± 49 vs 242 ± 72 ms, P < 0.001), e' (5.7 ± 2.0 vs. 6.6 ± 1.8 cm/s, P = 0.001), and a' (6.5 ± 2.0 vs. 7.6 ± 1.5 cm/s, P < 0.001) compared to the controls, and higher E/e' (13.3 ± 4.7 vs. 11.1 ± 3.5, P < 0.001). Thus, there were indications of pseudo normalization and increased filling pressure in the T2DM group, whereas the controls had evidence for relaxation abnormalities without elevated filling pressure. Compared to a non-diabetic obese group, more advanced subclinical impairment of diastolic function was seen in T2DM.

The aim of this study was to determine predictors of cardiovascular complications of arterial hypertension (AH) and type 2 diabetes mellitus (T2DM) and investigate the prognostic potential of catestatin (CST) and relaxin-2 (RLN-2) in this patient population. Materials and methods. The research was performed in accordance with all ethical principles of the Declaration of Helsinki. All study participants signed a written informed consent. This study involved 106 patients with primary hypertension and 30 healthy volunteers. 55 hypertensive patients had comorbid T2DM. Plasma CST and RLN-2 levels were measured by an enzyme-linked immunosorbent assay. Major adverse cardiovascular events (MACE) were collected during 12-month follow-up via telephone interviews at visits in months 3, 6, 9, and 12. The end points of this study were acute myocardial infarction, ischemic stroke, acute heart failure and cardiac death. Statistical data analysis was performed using the SPSS 25.0 statistical software. Results. 13 end-points were registered in patients with AH during the 12-month follow-up period, but the difference in frequency of MACE occurrence between patients with AH and T2DM and hypertensive patients without T2DM was insignificant (p=0.181). The Cox proportional hazard model indicated CST (p=0.01), but not RLN-2 (p=0.20), as an independent predictor of MACE in hypertensive patients. Age (p=0.01), AH duration (p=0.03), presence of T2DM (p=0.03), HOMA-IR index (p=0.02), insulin (p=0.02) and uric acid levels (p=0.02) were also established as independent factors of end-points occurrence. Conclusions. CST is an independent factor for predicting cardiovascular complications of AH, which allows us to consider it as a prognostic biomarker in patients with AH, especially hypertensive patients with comorbidity T2DM

Background In contrast to type 2 diabetes mellitus (DM), cardiac and vascular abnormalities in type 1 DM (T1DM) are not well investigated. We aimed to evaluate occurrence of cardiac remodeling, arterial stiffness and blood pressure (BP) phenotypes in T1DM patients. Methods The cross-sectional study consecutively included T1DM patients 18–44 y.o. without known CVD, in whom 24-hour monitoring of peripheral and central BP (ABPM) with BPLab Vasotens, applanation tonometry and conventional and speckle tracking echo were performed. BP phenotypes were determined according to current guidelines, PWV and CBP - according to individual reference values. Presence of systolic dysfunction was defined as global longitudinal strain (GLS) &lt;20%, left ventricular hypertrophy (LVH) as LV myocardial mass index (LVMI) &gt;95/&gt;115 g/m2 for women/men, LV remodeling (LVR) as RWT ≥0.43. P&lt;0.05 was considered significant. Results A total of 125 patients with T1DM (mean age 29,2±7,6 years, 60% male, median duration of DM 6,9 [2; 11] years, HbA1c 9.9 [6; 12] %, mean BMI 23±3 kg/m2, smoking 39%, median GFR 100 [86; 117] ml/min/1.73 m2, GFR &lt;60 ml/min/1.73 m2 – in 8.8%, median albuminuria 19 [8; 24] mg/g (moderate and high albuminuria in 14.6% and 2.2%) were investigated. According to office BP and ABPM hypertension (HTN) was diagnosed in 28% patients (true and masked in 4.8 and 23.2%, respectively) and true normotension in 72%. Isolated nocturnal HTN was observed in 14.4%. Majority of the patients were dippers (51.2%), non-dippers and night-peakers profiles were registered in and 43.2% and 5.6%, respectively. Central SBP and PWV elevation were observed in 17.6% and 57.6% (PWV &gt;10 m/s - only in 2.4%). Cardiac abnormalities were revealed in 72.4% of patients: GLS&lt;20%, LVH, LVR and diastolic dysfunction (DD) in 71.2, 12, 39.2 and 16.8% patients, respectively. Isolated GLS &lt;20% was detected in 30%, combination of GLS&lt;20% with LVH (or LVR) and DD in 47.2%. Patients with vs without HTN were characterized by higher PWV (7.8±1.5 vs 6.9±1.2, p&lt;0.001), LVMI (89.9 [75; 96] vs 71.5 [64; 77] p&lt;0.001), incidence of DD (29.6 vs 12.2%, p=0.03), LVH (28 vs 6%, p=0.002), trend towards higher rate of central SBP increase (32.7% vs 17.4%, p=0.08), lower incidence of LVR (26 vs 44%, p=0.002) and similar GLS (p=0.16). Groups with vs without nocturnal HTN did not differ by PWV, central SBP, GLS and LVMI. PWV increase was associated only with higher LVMI (88.2 [69; 95] vs 77.6 [68; 83], p=0.042). Correlations (p&lt;0.05) with albuminuria were observed for GLS (r=−0.26), DD (r=0.22) and non-dipping state (r=−0.34). GFR correlated (p&lt;0.05) with GLS (r=−0.32) and PWV (r=−0.32). Conclusion Incidence of prognostically unfavourable phenotypes of HTN, cardiac remodeling and arterial stiffness (even in patients without HTN) were relatively high in T1DM population. GLS and non-dipping state correlated with albuminuria, GLS and PWV with GFR

Objective — to evaluate the peculiarities of electrocardiographic (ECG) and echocardiographic (EchoCG) parameters in patients with essential hypertension (EH) in combination with type 2 diabetes mellitus (T2DM) and their relationships with plasma catestatin (CTS) and relaxin­‑2 (RLN­­2) levels. Materials and methods. Examinations involved 106 patients with EH, from whom 55 subjects had concomitant T2DM, and 30 practically healthy volunteers. The mean age of the participants was (64.06±8.44) years, and women prevailed in the patients’ group (55.9%). All study participants underwent anthropometric data measurement, laboratory and instrumental investigations. The levels of biomarkers CTS and RLN­­2 were determined with the enzyme‑linked immunosorbent assay. Instrumental investigations included electrocardiography and transthoracic echocardiography. Results. CTS levels were reduced in patients with concentric (5.04±1.14 ng/mL) and eccentric left ventricular hypertrophy (LVH) (5.08±0.89 ng/mL) compared with the normal geometry (6.63±0.73 ng/mL, p &lt;0.001). The significant correlation has been established between CTS levels and ECG parameters of LVH (Cornell voltage criterion (r=–0.222; p=0.009) and Sokolow‑Lyon index (r=–0.226; p=0.008)), and EchoCG parameters, including LV end‑diastolic dimension (EDD (r=–0.388; p &lt;0.001), LV end‑systolic dimension (ESD (r=–0.453; p &lt;0.001), LV end‑diastolic volume index (EDVi (r=–0.329; p &lt;0.001), LV end‑systolic volume index ESVi (r=–0.415; p &lt;0.001), LV ejection fraction (EF (r=0.469; p &lt;0.001), septal sickness (SS) (r=–0.593; p &lt;0.001), posterior wall thickness (PWS) (r=–0.647; p &lt;0.001), relative wall thickness (RWS) (r=–0.568; p &lt;0.001), and LV myocardial mass index (LVMi) (r=–0.576; p &lt;0.001). Patients with RLN­­2 ≥ 4.69 pg/mL had higher EchoCG parameters, including LV EDD, LV ESD, LV EDVi, LV ESVi, SV, SS, PWS, RWS, LVMi (p &lt;0.05). In addition, a significant positive relationship between CTS and RLN­­2 levels has been revealed (r=0.191; p=0.026), which was also confirmed in the subgroup of patients with RLN­­2 levels above 4.69 pg/mL (r=0.585; p &lt;0.001). Conclusions. The decrease in CTS levels at LVH and established correlations with the ECG signs of LVH and EchoCG parameters allow us to consider CTS as a predictor of the development of LVH, especially in patients with EH combined with T2DM.

Introduction Prediabetes and type 2 diabetes mellitus (T2DM) are risk factors for heart failure (HF). The association of prediabetes and T2DM to different forms of functional left ventricular impairment and their impact on clinical outcome in the general population needs to be further investigated. In this context, little is known about the prevalences of prediabetes and different HF subtypes in the general population, especially in Europe. Purpose To investigate the prevalence and clinical impact of prediabetes and type 2 diabetes mellitus (T2DM) on functional cardiac disorder (FCD). Methods The participants of the Gutenberg Health Study sample (15,010 subjects, 35–74 years) were stratified in individuals with euglycaemia, prediabetes and T2DM based on clinical information and HbA1c level. FCD included asymptomatic systolic and diastolic dysfunction, symptomatic systolic and diastolic heart failure, asymptomatic diastolic dysfunction and preserved left ventricular ejection fraction (EF), asymptomatic diastolic dysfunction and reduced EF, asymptomatic preserved diastole and reduced EF, symptomatic heart failure with preserved EF (HFpEF) and symptomatic heart failure with reduced EF HFrEF). Using structured follow-up clinical outcome was assessed. Results Overall, 14,870 individuals were included in the present analysis. Among them, 9,426 individuals were categorized in the euglycaemia group, 4,128 participants had prediabetes and in 1,316 individuals T2DM was present. Prevalence of FCD increased from euglycaemia (19.6%) over prediabetes (33.3%) to T2DM (46.8%, p&amp;lt;0.0001). Prevalence of symptomatic HF was increased in patients with T2DM (euglycaemia 2.8%, prediabetes 5.9%, T2DM 11.9%). T2DM was associated with reduced EF (β −0.63, 95% CI −0.99 to −0.26, P=0.00088) and elevated E/E' (β 0.08, 95% CI 0.06 to 0.10, P&amp;lt;0.0001), whereas prediabetes was associated to elevated E/E' (β 0.02, 95% CI 0.01 to 0.03, P=0.0029). Prediabetes and T2DM revealed increased prevalences of FCD (13%, 18%), asymptomatic diastolic dysfunction with preserved EF (prediabetes: 14%, T2DM: 11%), symptomatic heart failure (prediabetes: 46%, T2DM: 70%) and HFpEF (prediabetes: 49%, T2DM: 82%). With prediabetes and T2DM all-cause mortality was elevated in presence and absence of FCD, only T2DM was also a risk factor for cardiovascular mortality with and without FCD. Within a 5-years follow-up, T2DM was an independent risk factor for the development of FCD, asymptomatic diastolic dysfunction with reduced ejection fraction, symptomatic heart failure and HFrEF. Prediabetes was not an independent risk factor for FCD. Conclusions In the general population, a high prevalence of asymptomatic FCD is present. Coexisting FCD and prediabetes as well as T2DM result in increased mortality elucidating the need for early detection and prevention of DM development, especially with regard to numerous asymptomatic people concerned. T2DM, but not prediabetes, is a risk factor for incident FCD. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The Gutenberg Health Study is supported by the government of Rheinland-Pfalz (`Stiftung Rheinland-Pfalz für Innovation'), the research programmes `Wissen schafft Zukunft' and the Centre forTranslational Vascular Biology (CTVB) of the Johannes Gutenberg-University of Mainz, Germany, and its contract with Boehringer Ingelheim and Philips Medical Systems including an unrestricted grant forthe Gutenberg Health Study. P.S.W. and J.H.P. are funded by the Federal Ministry of Education and Research (BMBF 01EO1503). P.S.W. and T.M. are principal investigators of the German Center for Cardiovascular Research (DZHK). P.S.W. is principal investigator of the DIASyM research core (BMBF 161L0217A).

The global epidemic of type 2 diabetes mellitus (T2DM) has substantial implications for cardiovascular disease–related morbidity and mortality.1 The prevalence of T2DM in patients with heart failure (HF) is high, with strong and independent association between T2DM and incident HF observed in multiple prospective studies and in randomized-controlled clinical trials. In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), which enrolled subject’s ≥55 years of age with hypertension and ≥1 risk factor, patients with T2DM had a 2-fold risk for HF hospitalization or death after adjustment for other risk factors (RR, 1.95). The association with T2DM was independent of coronary artery disease and at least equivalent in magnitude and greater than that for electrocardiographic left ventricular (LV) hypertrophy.2 All measures of glycemia including fasting, postprandial, measures of insulin resistance, and hemoglobin A1c (HbA1c) have been associated with risk of developing HF, with the association extending to both HF with preserved ejection fraction and to HF with reduced ejection fraction.3,4 A substantial body of evidence from preclinical studies, endomyocardial biopsies in humans and more recently with cardiac MRI, support increased myocardial stiffness in T2DM related to alteration in extracellular matrix. There are multiple proximate mediators that have been hypothesized to play a role including advanced glycation end product deposition and reactive oxygen species that may increase myocardial stiffness during diastole, by cross-linking collagen or by enhancing collagen formation.5,6 Another pernicious proximal mediator is the elevation in postprandial lipids, such as remnant lipoproteins, characteristic of atherogenic dyslipidemia, a highly prevalent abnormality in T2DM, that may result in direct myocellular deposition of lipid, leading to microcirculatory dysfunction, alteration in substrate use and mitochondrial dysfunction.7,8 Indeed, positron emission tomography studies show reduced myocardial glucose uptake in favor of fatty acid …

Sodium-glucose co-transporter 2 inhibitors in heart failure with preserved ejection fraction: reasons for optimism.

<i>Circulation</i> Editors’ Picks

Hypertension (HTN), defined as a blood pressure of greater than or equal to 140/90 mmHg, is the leading risk factor for cardiovascular disease worldwide, and its prevalence has doubled since 1990.1 Despite unmistakable evidence that blood pressure control decreases the morbidity and mortality of HTN and the availability of safe, effective, and affordable pharmacologic medications, the global control rate is only approximately 20%. More ominous is the recent observation that in high-income countries such as the United States (US), the control rate of HTN has declined from approximately 55% to 47% over the last decade. Within individuals with HTN are those with "resistant HTN", defined as a blood pressure that remains above treatment goal despite the use of three anti-hypertensive medications from recommended classes at maximal doses, including one of which is a thiazide or thiazide-like diuretic. Approximately 10% of US adults with HTN have resistant HTN. Those with resistant HTN are more predisposed to adverse cardiovascular outcomes.2-5 The morbidity and mortality from HTN are primarily related to target organ damage, such as the heart, brain, kidney, and vasculature. Cardiac damage includes coronary artery disease resulting in myocardial infarction, congestive heart failure, and left ventricular hypertrophy (LVH). LVH is often overlooked and is related to cardiac remodeling from pressure-overload. While initially compensatory, LVH is ultimately deleterious by leading to congestive heart failure, arrhythmias, and sudden cardiac death. Initially, the ejection fraction is preserved through processes resulting in diastolic dysfunction and increasing left ventricular filling pressures leading to heart failure with preserved ejection. If the elevated blood pressure remains untreated or poorly controlled, this eventually progresses to a reduction in ejection fraction. The prolonged exposure to an elevated blood pressure increases left ventricular afterload and peripheral vascular resistance leading to structural remodeling.6, 7 Increased left ventricular mass (LVM) causes increased myocardial stiffness, increased left ventricular end-diastolic pressure, impaired relaxation, and left atrial dilation.8 These structural changes result in diastolic dysfunction, which can be quantified using echocardiography9 and, more accurately, with cardiac MRI.10 In this issue of the journal, Matanes and colleagues contribute to our body of knowledge regarding cardiac structure and function in resistant HTN and the potential beneficial role of blood pressure reduction. The authors hypothesized that resistant HTN is associated with higher LVM resulting in an increased prevalence of LVH, larger intracardiac volumes, and thus, chamber dilation, and greater diastolic dysfunction when compared to those with controlled non-resistant HTN. Controlled resistant HTN was defined as an office blood pressure less than or equal to 135/85 mmHg on at least three consecutive follow up visits while taking four or more antihypertensive medications, including a thiazide or thiazide-like diuretic. Importantly, this group of controlled resistant HTN was compared to a group of patients with controlled HTN without resistant HTN. A total of 182 patients met inclusion criteria after appropriate screening for secondary causes of HTN. The final cohort comprised of 132 patients after excluding those with masked HTN. Those with masked HTN, defined as having a high out of office blood pressure but normal office blood pressure, was studied separately. Blood pressure readings were taken unattended with appropriate technique. A total of six readings were performed, each 1 minute apart, and the average of the last five readings was used as the final reading. In addition to determining LVH and left ventricular mass index (LVMI), cardiac MRI was used to assess left ventricular peak filling rate (PFR), diastolic volume recovery (DVR), left atrial volume index (LAVI), and E (early) and A (atrial) wave filling velocities, all of which are measures of diastolic function.10 The results demonstrated that a higher prevalence of type 2 diabetes mellitus (42% vs. 15.9%, p = .001), a higher 24-hour ambulatory pulse pressure (61.5 ± 12.1 vs. 56.8 ± 10.8, p = .020), and a lower estimated glomerular filtration rate (56.8 ± 25.3 vs. 72.6 ± 26.5, p = .004) were observed in the controlled resistant HTN group as compared to the controlled non-resistant HTN group. Of interest, left ventricular systolic function and diastolic function were similar between the two groups. There also was no significant difference in left ventricular end-diastolic and end-systolic volume index, left atrial volumes, left ventricular stroke volume/pulse pressure ratio, and brain natriuretic peptide levels between the two groups after controlling for those with masked HTN. The authors hypothesized that the administration of more intensive thiazide, or thiazide-like diuretic, and mineralocorticoid antagonist administration in the controlled resistant HTN group improved volume status and/or contributed to a further reduction in blood pressure resulting in improved diastolic dysfunction in the controlled resistant HTN group. The findings also demonstrated similar intracardiac volumes between the controlled resistant HTN and controlled non-resistant HTN groups. Those with controlled resistant HTN did have a significantly higher LVM versus the controlled non-resistant HTN group (135.5 g ± 55.7 vs. 118.2 g ± 32.8, p = .031, respectively) and posterior wall thickness (8.5 mm ± 2.2 vs. 7.6 mm ± 1.5, p = .005, respectively), as measured by cardiac MRI. Further analysis was performed on the subgroup determined to have masked HTN. Individuals were categorized as having either masked uncontrolled non-resistant hypertension (MUCH) or masked uncontrolled resistant hypertension (MRHTN). Individuals with MUCH or MRHTN were found to have higher LVM (in grams) when compared to those with controlled HTN. Additionally, MRHTN was associated with higher LVMI when compared to those with controlled resistant HTN. The only cases of LVH found in the study were found in the MRHTN group. MRHTN patients also had higher BMIs (34.4 ± 4.7 vs. 31.4 ± 5.4, p = .019) and a higher prevalence of type 2 diabetes mellitus (54.1% vs. 28.1%, p = .030). This paper demonstrates that when blood pressure in individuals diagnosed with resistant HTN is controlled and those with masked HTN are excluded, there is no difference in mean LVM, LVH, and systolic or diastolic dysfunction when compared to patients with controlled non-resistant HTN. This implies that controlling blood pressure in resistant HTN may reverse an existing increase in LVM and improve diastolic function. It is important to note that the blood pressures achieved in this paper were remarkable in that the systolic blood pressure of those with controlled resistant HTN and controlled HTN were approximately equal at 118 and 117 mmHg, respectively. The results seen in this study are like those seen in SPRINT, which demonstrated that intensive blood pressure reduction significantly reduced morbidity and mortality greater than in those with standard blood pressure reduction.11 Of note, SPRINT enrolled individuals had higher cardiac risk, were older (approximately 68 years old), and had a higher prevalence of chronic kidney disease. Furthermore, they were on an average of two anti-hypertensive medications at baseline and typically required on average an additional third medication to achieve a further reduction of systolic blood pressure in the intensive group. Additionally, most of the benefit from intensive blood pressure reduction was in a reduction of congestive heart failure, likely due to a reduction of diastolic dysfunction and heart failure with preserved ejection fraction. Thus, the degree of blood pressure control, especially in those with resistant HTN and other high-risk individuals with HTN including older individuals who are also at risk for diastolic dysfunction, may be the most crucial finding in the beneficial results seen in this present study. The intensively controlled blood pressures seen may also limit the application of these findings to centers with more experience and expertise in the management of resistant HTN. Limitations of the study include a small sample size and patients' self-reported non-adherence to anti-hypertensive medications. Internal validity, however, was maintained with subgroup analysis and controlling for other clinical factors that promote LVH. Increased LVM is a significant predictor of cardiovascular adverse events and mortality,12-14 and this study highlights the utility of using cardiac MRI to evaluate hypertensive cardiac disease. Cardiac MRI, however, is not available in every clinical setting, is time-consuming, and costly which limits external validity. Cardiac doppler echocardiography may also be more readily available in these settings. This study emphasizes further the importance and benefit of achieving blood pressure control in all individuals with the diagnoses of HTN and potentially establishing a lower blood pressure treatment threshold and target as control for those at elevated risk. The recent World Health Organization 2021 Guidelines for the Pharmacological Treatment of the Adult with HTN emphasize a lower blood pressure treatment threshold (> or = to 130 mmHg) and target (<130 mmHg) in those with known cardiovascular disease as well as those with high cardiovascular risk by calculation, diabetes mellitus, and chronic kidney disease.15 Furthermore, controlled resistant hypertensive patients can improve cardiac structure and function to those with controlled non-resistant hypertensive levels. Finally, the results of this paper demonstrate that patients with dyslipidemia had diastolic filling patterns suggestive of diastolic dysfunction regardless of the degree of blood pressure control. This emphasizes the importance of controlling all present cardiovascular risk factors in an integrated approach together with the control of HTN. Neil D. Mehta, Sean J. Battle and Donald J. DiPette: authors, editors. Donald J. DiPette MD, FAHA, FACP is a Distinguished Health Sciences Professor at the University of South Carolina, School of Medicine, Columbia South Carolina. None to disclose.

BackgroundPatients with diabetes have an increased risk of developing heart failure with preserved ejection fraction (HFpEF). This study aimed to compare indices of myocardial deformation and perfusion between patients with type 2 diabetes mellitus (T2DM) with and without HFpEF and to investigate the relationship between myocardial strain and perfusion reserve.MethodsThis study included 156 patients with T2DM without obstructive coronary artery disease (CAD) and 50 healthy volunteers who underwent cardiac magnetic resonance (CMR) examination at our center. Patients with T2DM were subdivided into the T2DM–HFpEF (n = 74) and the T2DM–non-HFpEF (n = 82) groups. The parameters of left ventricular (LV) and left atrial (LA) strain as well as stress myocardial perfusion were compared. The correlation between myocardial deformation and perfusion parameters was also assessed. Mediation analyses were used to evaluate the direct and indirect effects of T2DM on LA strain.ResultsPatients with T2DM and HFpEF had reduced LV radial peak systolic strain rate (PSSR), LV circumferential peak diastolic strain rate (PDSR), LA reservoir strain, global myocardial perfusion reserve index (MPRI), and increased LA booster strain compared to patients with T2DM without HFpEF (all P < 0.05). Furthermore, LV longitudinal PSSR, LA reservoir, and LA conduit strain were notably impaired in patients with T2DM without HFpEF compared to controls (all P < 0.05), but LV torsion, LV radial PSSR, and LA booster strain compensated for these alterations (all P < 0.05). Multivariate linear regression analysis demonstrated that LA reservoir and LA booster strain were independently associated with global MPRI (β = 0.259, P < 0.001; β = − 0.326, P < 0.001, respectively). Further, the difference in LA reservoir and LA booster strain between patients with T2DM with and without HFpEF was totally mediated by global MPRI. Global stress PI, LA booster, global rest PI, and global MPRI showed high accuracy in diagnosing HFpEF among patients with T2DM (areas under the curve [AUC]: 0.803, 0.790, 0.740, 0.740, respectively).ConclusionsPatients with T2DM and HFpEF exhibited significant LV systolic and diastolic deformation, decreased LA reservoir strain, severe impairment of myocardial perfusion, and elevated LA booster strain that is a compensatory response in HFpEF. Global MPRI was identified as an independent influencing factor on LA reservoir and LA booster strain. The difference in LA reservoir and LA booster strain between patients with T2DM with and without HFpEF was totally mediated by global MPRI, suggesting a possible mechanistic link between microcirculation impairment and cardiac dysfunction in diabetes. Myocardial perfusion and LA strain may prove valuable for diagnosing and managing HFpEF in the future.

The objective: to investigate the impact of hypertensive disease (HD) and concomitant type 2 diabetes mellitus (T2DM) on the quality of life (QOL) of patients using the SF-36 questionnaire and to evaluate the peculiarities of the QOL parameters depending on plasma relaxin-2 (RLN-2) and catestatin (CTS) levels. Materials and methods. The study was conducted in accordance with the principles of the Declaration of Helsinki. 136 patients took part in the study: 106 patients with HD and 30 healthy volunteers. The patients with HD were divided into two groups. The first group included 55 patients with HD and T2DM, the second group – 51 persons with HD without T2DM. Each study participant underwent a comprehensive clinical, laboratory and instrumental examinations. All participants filled out quality of life SF-36 questionnaire and the questionary of HD patient. Concentrations of CTS and RLN-2 in blood plasma were determined by enzyme immunoassay method (E4996Hu, BT Lab, Shanghai, China and E-EL-H1582, Elabscience, USA, respectively). All patients filled the home blood pressure monitoring diaries for 31 days. Statistical data analysis was performed using the SPSS 25.0 statistical program. Results. The patients with HD had lower parameters of physical and mental components of health compared to healthy volunteers (p&lt;0.005). It was found that the presence of concomitant T2DM leads to even a greater decrease in quality of life indicators than in patients with HD without carbohydrate metabolism disorders (p&lt;0.05). In patients with RLN-2 levels ≥4.69 pg/ml the lower parameters of the physical component of health (p&lt;0.05) and social functioning (p=0.012) were determined. Lower CTS scores are associated with lower QOL scores (p≤0.005). Significant negative correlations were found between average SBP (aSBP) and indicators of physical and mental components of health (p&lt;0.001), while mean DBP had correlations only with general health and total physical component of health (p&lt;0.05). Conclusions. HD leads to a decreased QOL of patients, which is confirmed by lower scores of the SF-36 questionnaire and established negative correlations between aSBP and QOL parameters. The presence of concomitant T2DM is associated with even a greater decline in physical and mental health components.