Aim – to identify the specifics of age-related changes and combinations of metabolic disorders in the risk of developing cardiovascular events among rural residents of the Orenburg region. Material and methods. 499 people aged 35 to 74 years participated in the study. The follow-up period was 36 months. All patients underwent an analysis of age, anthropometric and metabolic parameters (body mass index, body obesity index, visceral obesity index, atherogenicity index, insulin resistance). Results. During the analysis of variance, patients of advanced age manifested a statistically significant difference from young and elderly patients in terms of the level of fatal complications (p=0.002). Elderly patients showed a statistically significant difference from young and advanced age patients in terms of the level of nonfatal events. Conclusion. The role of age-related changes as the only predictor of the development of cardiovascular events remains controversial. The identification of single factors of metabolic imbalance also has a low informational value. An increase in the number of metabolic deviations will determine the course and prognosis of an active person’s life. Patients aged 45 to 59 years are exposed to a more aggressive influence of metabolic predictors of the development of cardiovascular events due to insufficient formation of adaptive mechanisms in the aging process.

Arterial hypertension (AH) is a global health problem due to its increasing prevalence and due to life-threatening complications. Currently, the World Health Organization claims that one in four men and one in five women suffer from hypertension, that is, more than 1 billion people. Almost every second patient knows about their disease status, while less than 40% of patients in Europe demonstrate adequate blood pressure control with a target level of <140/90 mm Hg, despite antihypertensive treatment. With age, the prevalence of the disease increases and reaches 50–65% in people over 65 years of age. The aim of the study was to identify the frequency of new cases of arterial hypertension, depending on the presence of risk factors for cardiovascular diseases in the rural population of the Orenburg region. Materials and methods. 504 people aged 35 to 75 years participated in the study. The follow-up period was 24 months. The patients' health status was monitored using a standard questionnaire, clinical blood analysis, glycemia and total cholesterol, and an ECG in 12 standard leads. The assessment of the occurrence of new cardiovascular events took place after 2 years. All participants underwent a repeat survey, blood glycemia and cholesterol control. Results. The analysis revealed a positive relationship between the occurrence of hypertension and OT/O (p=0.006), as well as the dependence of hypertension and smoking.

Russian Society of Cardiology (RSC)With the participation: National Society of Myocardial Diseases and Heart Failure, Society of Heart Failure Specialists, Russian Scientific Medical Society of Internal MedicineEndorsed by the Research and Practical Council of the Ministry of Health of the Russian Federation (12.09.2024)

Dietary habits affect the risk of all-cause mortality (ACM) in the adult population according to prospective studies.Aim. To assess the effect of dietary habits on the ACM risk in the Rus­sian population.Material and methods. The prospective cohort included represen­ta­tive samples of 10 Russian regions (n=17175, 6767 men and 10408 wo­men aged 25-64 years), examined in 2012-2014 as part of the ESSE-RF study. Dietary habits were studied based on the consumption rate of the main food groups. The vital status of the cohort was updated every 2 years. The follow-up period was 6 years. Kaplan-Meier curves were used to analyze overall survival (OS). Cox proportional hazards model was used to assess the ACM risk.Results. In the Russian population, an increase in OS is associated with daily consumption of vegetables/fruits, dairy products (milk, kefir, yogurt, cottage cheese, and cheese), and the presence of the Heal­thy Eating Model (HEM) in the diet. A decrease in OS is associated with excess salt intake (ESI) in the diet, the habit of adding salt to pre­pared foods, and daily consumption of pickles (p<0,05). Among men, an increase in OS is observed with daily consumption of fruits/ve­ge­tables, cheese, and HEM, while a decrease is observed with daily consumption of pickles, general ESI, and the habit of adding salt to foods (p<0,05). In women, daily consumption of red meat, liquid dairy products, cheese, and sweets is associated with an increase in OS (p<0,05). The risk of ACM in the general population and among men increases with ESI — relative risk (RR)=1,31 [1,06-1,61] (p=0,012) and 1,41 [1,06-1,87] (p=0,017), respectively, adding salt to food — RR=1,34 [1,09-1,65] (p=0,006) and 1,5 [1,13-1,98] (p=0,005) and daily consumption of pickles — RR=1,48 [1,02-2,14] (p=0,039) and 1,5 [1,01-2,54] (p=0,045). In women, regular consumption of red meat — RR=0,7 [0,49-0,99] (p=0,043), liquid dairy products — RR=0,68 [0,5-0,93] (p=0,015) and cheese — RR=0,64 [0,46-0,9] (p=0,011) were associated with an ACM decrease.Conclusion. An ACM risk increase in the general population and among men is associated with excess salt intake, and a decrease in ACM risk in women is associated with the regular inclusion of red meat and dairy products in the diet.

The population of Russia consists of more than 150 local ethnicities. The ethnic diversity and geographic origins, which extend from eastern Europe to Asia, make the population uniquely positioned to investigate the shared properties of inherited disease risks between European and Asian ancestries. We present the analysis of genetic and phenotypic data from a cohort of 4,145 individuals collected in three metro areas in western Russia. We show the presence of multiple admixed genetic ancestry clusters spanning from primarily European to Asian and high identity-by-descent sharing with the Finnish population. As a result, there was notable enrichment of Finnish-specific variants in Russia. We illustrate the utility of Russian-descent cohorts for discovery of novel population-specific genetic associations, as well as replication of previously identified associations that were thought to be population-specific in other cohorts. Finally, we provide access to a database of allele frequencies and GWAS results for 464 phenotypes.

Research data indicate an increase in the risk of cardiovascular events (CVEs) with unhealthy diet.Aim. To assess the impact of diet on the development of cardiovascular events in the Russian population.Material and methods. The prospective cohort included representative samples of 10 Russian regions (n=17175, 6767 men and 10408 women aged 25-64 years), examined in 2012-2014 as part of the ESSE-RF study. The diet was studied by the frequency of consumption of the main food groups. The vital status of the cohort was clarified every 2 years. The follow-up period was 6 years. Kaplan-Meier survival curves were used to analyze survival, and the Cox proportional hazards model was used to assess the risk of CVEs.Results. Analysis of Kaplan-Meier curves showed better survival before the CVEs in the general population with daily consumption of cottage cheese (p=0,0029), cheese (p=0,00017), red meat (p=0,036) and the presence of the healthy eating model in the diet (p=0,013). A decrease in survival before the CVE onset was noted with excess salt intake (ESI) in the diet (p=0,0038) and the habit of adding salt to food (p=0,0032).Among men, a decrease in survival before the CVE onset was noted with ESI (p=0,018) and the habit of adding salt to food (p=0,047), and an increase — with regular consumption of red meat (p=0,00027). Among women, daily consumption of red meat (p=0,038), cheese (p=0,026), cottage cheese (p=0,019), as well as rare consumption of fatty dairy products (sour cream/cream) (p=0,04) delay the CVE onset. In the general population, in a univariate Cox proportional hazards analysis, daily cheese consumption and healthy eating model significantly reduce the risk of CVEs — 0,74 (0,61-0,89) and 0,78 (0,65-0,94), respectively, and excess salt and adding salt to food increase the CVE risk — 1,33 (1,12-1,59) and 1,33 (1,111,58), respectively. However, after introducing correction for socio-demographic indicators and risk factors, the significance is lost. In men, adding salt to food significantly increases the risk of cardiovascular events as follows: odds ratio 1,34 (1,04-1,73). Other eating habits are significant only in univariate analysis and lose their significance after introducing corrections.Conclusion. Adding salt to food significantly increases the risk of cardiovascular events among men of active working age.

The Russian Society of Cardiology (RKO)With the participation of: Russian Scientific Medical Society of Internal Medicine (RSMSIM)Approved by the Research and Practical Council of the Ministry of Health of the Russian Federation (12.09.2024)

Aim. To evaluate the contribution of arterial hypertension (AH), high lowdensity lipoprotein cholesterol (LDL-C) level and their combination to the development of (myocardial infarction) MI and stroke.Material and methods. The analysis is based on data from 1 and 2 observations of ESSE-RF study (Epidemiology of cardiovascular diseases in various regions of the Russian Federation)". A multi-s tage cluster random sample was used, formed according to the territorial principle on the basis of medical and preventive institutions (health facilities). Socio-demographic data (gender, age, education, wealth), smoking status and medical history were determined. Blood pressure (BP) was measured twice, on the right arm, in a sitting position with an automatic blood pressure monitor. Blood samples and its derivatives (serum and plasma) were stored at a temperature of -70ºC. LDL-C value was also included into analysis (LDl- C ≥3 mmol/l). Prospective monitoring of new cases was carried out in the initial sample without patients with coronary artery disease, MI, and stroke. The median follow-up time is 7.5 years. The sample size was 19 794. 356 non-fatal cases were identified, including 222 cases of MI and 174 cases of stroke.Results. The average age was 44.7 years, in men — 43.2, and in women — 45.3. The prevalence of isolated forms of hypertension, high LDL-C level and its combination were 12.7%, 30.3% and 32%, respectively. It was revealed that the age was the lowest in healthy and those with an increased LDL-C, whereas those with hypertension and combined conditions were older. The risk of nonfatal cases of MI and stroke in the Cox models, was adjusted for gender, age and region. There was a significantly higher risk of new cases of nonfatal CVD in individuals with isolated hypertension compared with those with isolated LDL-C.Conclusion. The frequency of isolated AH and isolated LDL-C were 13% and 30%, respectively. The combined condition was detected in 30%. The presence of AH, isolated LDL-C and their combinations in the sample doubled the risk of new CVD events.

The population of Russia consists of more than 150 local ethnicities. The ethnic diversity and geographic origins, which extend from eastern Europe to Asia, make the population uniquely positioned to investigate the shared properties of inherited disease risks between European and Asian ethnicities. We present the analysis of genetic and phenotypic data from a cohort of 4,145 individuals collected in three metro areas in western Russia. We show the presence of multiple admixed ancestry clusters spanning from primarily European to Asian and high identity-by-descent sharing with the Finnish population. As a result, there was notable enrichment of Finnish-specific variants in Russia. We illustrate the utility of Russian-descent cohorts for discovery of novel population-specific genetic associations, as well as replication of previously identified associations that were thought to be population-specific in other cohorts. Finally, we provide access to a database of GWAS results for 465 unique phenotypes and allele frequencies.

Acute dissection of aortic refers to cardiovascular catastrophes accompanied by a high level of fatal complications and deaths. In the vast majority of cases, middle-aged and elderly men with a burdened history of arterial hypertension and atherosclerosis suffer from this ailment. However, in addition to these diseases, this pathology can occur with rheumatism, inflammatory vascular diseases and connective tissue diseases. The polysymptomicity of the disease provides a high probability of meeting with this pathology of doctors of any specialization. Focusing on the clinical manifestations of the disease, taking into account laboratory (activation of prothrombotic and fibrinolytic mechanisms of the hemostasis system) and instrumental data will direct to timely recognition of pathology and diagnosis, which will determine the tactics of management and prognosis of the patient’s life. The disease in question is an absolute indication for surgical treatment, therefore conservative therapy will be aimed only at stabilizing hemodynamic parameters and preparing for surgical treatment of the patient. A clinical case of dissection of an aortic aneurysm, which occurred under the masks of acute coronary syndrome and acute abdomen, is presented. This case demonstrates the importance of assessing clinical symptoms and the dynamics of their development in the diagnosis of acute aortic dissection for doctors of both therapeutic and surgical profiles.

ОСОБЕННОСТИ КАРДИОЛОГИЧЕСКОГО СТАТУСА ПАЦИЕНТОВ С ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТЬЮ С СОХРАНЕННОЙ ФРАКЦИЕЙ ВЫБРОСА И САХАРНЫМ ДИАБЕТОМ 2 ТИПАДушина А

Idiopathic hypereosinophilic syndrome is a rare phenomenon in medical practice. The main criterion for diagnosis is a persistent increase in the level of eosinophils above 1.5 * 10 9 / l in the blood serum and the absence of clinical and laboratory and instrumental data explaining the possible nature of this condition. A clinical case of idiopathic hypereosinophilic syndrome, which occurs under the guise of acute coronary syndrome, is presented. A detailed analysis of this case was carried out in order to highlight a possible variant of the course of this disease, as well as to increase alertness in the area of “large” eosinophilia.

Background High plasma triglyceride (TG) is an independent risk factor for cardiovascular disease. Fibrates lower TG-levels through PPARα agonism. Currently available fibrates, however, have relatively low selectivity for PPARα. Objectives The aim of this trial was to assess the safety, tolerability and efficacy of K-877 (pemafibrate) —a selective PPARα modulator —in statin-treated European patients with hypertriglyceridemia. Methods A total of 408 statin-treated adults were recruited from 68 European sites for this Phase 2, randomized, double-blind, placebo-controlled trial. They had fasting TG between 175 and 500 mg/dL and HDL-C ≤50 mg/dL for men and ≤55 mg/dL for women. Participants were randomized to receive placebo or one of 6 pemafibrate regimens: 0.05 mg BID, 0.1 mg BID, 0.2 mg BID, 0.1 mg QD, 0.2 mg QD, or 0.4 mg QD. The primary endpoints were TG and non-HDL-C level lowering at Week 12. Results Pemafibrate reduced TG at all doses (adjusted p value <0.001) with the greatest placebo-corrected reduction from baseline to Week 12 observed in the 0.2 mg BID treatment group (54.4%). Reductions in non-HDL-C did not reach statistical significance. Reductions in TG were associated with improvements in other markers for TG-rich lipoprotein metabolism, including reductions in apoB48, apoCIII, and remnant cholesterol, and an increase in HDL-C levels. Pemafibrate increased LDL-C levels, whereas apoB100 was unchanged. Pemafibrate was safe and well-tolerated, with only minor increases in serum creatinine and homocysteine concentrations. Conclusion Pemafibrate is effective, safe, and well-tolerated for the reduction of TG in European populations with hypertriglyceridemia despite statin treatment.

Aim. To perform a population analysis of Non-High Density Lipoprotein Cholesterol level (non-HDL-c) in Russian population and to evaluate its association with cardiovascular events.Material and Methods. The material consisted of results obtained from 11 regions of the ESSE-RF1 Study and from 4 regions of the ESSE-RF2 Study. Study protocols were identical. The studies were performed in 2012-2014 and 2017, respectively. Endpoints were assessed in 19041 people aged 35-64 years. The median follow-up was 6.5 years in ESSE RF (1) and 3.8 years in ESSE RF(2). Analysis was performed for three lipid variables: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and non-HDLC in two samples: the general population sample and the same sample without individuals with coronary heart disease (CHD), myocardial infarction (MI) and/or stroke history and not taking statins (the population sample of "without a history of cardiovascular diseases [CVD]". The analysis of nonlinear associations was performed using the generalized additive Cox model. The combined cardiovascular endpoint was represented by cardiovascular death and nonfatal MI and stroke. Traditional and laboratory FRs, socio-demographic parameters were analyzed. The significance level for all tested hypotheses was set to be 0.05.Results. The prevalence of elevated non-HDL-C level (>3.7 mmol/l) was found to be 74.6%. No gender differences were found: there was 74.6% for men and 74.5% for women. Both mean values and prevalence of elevated non-HDL-C were increased with age in women, and its level was slightly decreased in men after 55 years old. Almost all analyzed RFs were significantly associated with elevated non-HDL-C in these two population samples. In both samples elevated total CH and elevated LDL-C were associated with all-cause mortality after correction for all RFs. On the contrary, the non-HDL-C was associated with CVD combined end pints. It has been shown that the risk of these end points increases uniformly with increase in levels of non HDL cholesterol, no nonlinear associations were found.Conclusion. The results of a population-based analysis of non-HDL-C performed in the Russian population for the first time confirmed that elevated non-HDL-C levels contribute significantly to determining the risk of cardiovascular events in the medium term. It can be assumed that the new risk scales (SCORE2 and SCORE OP) proposed by the European Society of Cardiology and the European Society of Preventive Cardiology, which include non-HDL C instead of TC, will allow adequate assessment of 10-year cardiovascular risk for Russians. However, continued monitoring of endpoints in order to obtain stable associations is required.

Background and hypothesisPhysical activity (PA) is an important behavioral factor associated with the quality of life and healthy longevity. We hypothesize that extremely low and extremely high levels of daily PA (including occupational PA) may have a negative impact on sleep quality and psychological well-being.ObjectiveThe aim of the study is to investigate the association between the level and type of PA and sleep problems in adult population.Materials and methodsThe sample of the study consisted of the participants from the population-based cohort of The Epidemiology of Cardiovascular Risk Factors and Diseases in Regions of the Russian Federation Study (ESSE-RF). The data of three regions (Saint Petersburg, Samara, Orenburg), varying in geographic, climatic, socioeconomic characteristics, was included into analysis. The total sample consisted of 4,800 participants (1,600 from each region; 1,926 males, 2,874 females), aged 25–64. The level of PA was evaluated using three parameters: the type of PA at work, the frequency of an intensive/high PA including sport (times a week), the mean duration of leisure-time walking (minutes a day). The measures of sleep quality were sleep duration and the frequency of difficulty falling asleep, difficulty maintaining sleep, daytime sleepiness, and sleep medication use. PA and sleep characteristics were assessed by interview carried by the trained medical staff.ResultsWhen controlling for gender, age and socioeconomic status (SES) extremely high occupational PA was a significant risk factor for difficulty falling asleep three or more times a week [OR(CI95%) = 1.9(1.2–3.0), p = 0.003] while working in a sitting position or having moderate physical load at work were not associated with sleep characteristics. Having a high physical load six or more times a week was a risk factor for difficulty falling asleep controlling for gender, age and SES [OR(CI95%) = 1.9(1.4–3.4), p = 0.001]. The association between leisure-time walking and sleep characteristics was insignificant. Walking less than an hour a day was associated with increased depression scores (46.5 vs. 41.9%, p = 0.006).ConclusionHigh physical load at work and excessively frequent intensive PA are associated with difficulties initiating sleep and may represent a risk factor for insomnia.

Abstract Introduction Cardiovascular diseases (CVD) are the most serious public health problem, remaining the leading cause of death in the adult population. A great number of CVD risk scales are successfully used in clinics, yet they are tuned to work the best for patients of older age and often are population specific. Methods We used the data from a longitudinal epidemiologic study of 4,750 individuals aged 25–64 years from European part of Russia recruited in 2012–2013 to predict the 10-year risk of cardiovascular events in Russian population and evaluate performance for common clinical risk scales. The cohort was divided into two groups: “cases” – individuals with a cardiovascular event registered during the follow up period (2013–2019) as a study group (N=106) and “controls” – individuals with no cardiovascular events registered during follow up as a control group (N=4,644). All individuals with previous history of CVD (ischemic heart disease, stroke or heart attack) prior to 2012 were assigned high risk in all scales. The case and control groups were split by age: below and above 40 to reflect the properties of cardiovascular risk scales to work best for age over 40. We assessed CVD risk scores using Framingham 2008 [1], ASCVD 2013, both were calculated with mean parameters values calculated from our cohort and from the original study [2], SCORE 2003, 2017 and 2019 [3] and MOSP - the recalibrated for Russian population scale of the SCORE 2017 [4] Results For patients over 40 years old, cardiovascular risk scales showed similar performance, with ASCVD normalized to the original study's mean parameter values returning the best prediction scores. Expectedly, for the younger group of patients, cardiac risk scales do not have notable predictive power. Further, we thought to identify additional factors discriminating young individuals at higher risk of CVD. We downsampled the control cohort to include only samples with age, weight, height, LDL, total cholesterol and systolic blood pressure matching those in a case cohort (<40 years of age). 186 phenotypic features were tested and 4 out of top 10 (p<0.05) associated features included questions related to depression, anxiety or current stress level from HADS scale, though not significant after multiple hypothesis correction, this suggests that younger individuals with high scores in depression/anxiety screenings might be at higher risk of CVD. Depression/anxiety features were added to cardiovascular risk scales as binary predictor components to improve prediction quality (Table 1). Conclusions We identified depression and anxiety screening questionnaires as a valuable predictor for cardiovascular events in the younger population improving the quality of predictions of traditional clinical scales. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Science and Higher Education of the Russian Federation Table 1. ROC analysis

Aim. To study the associations of subclinical and clinical anxiety and depression, assesed by the Hospital Anxiety and Depression Scale (HADS), ≥8 points and ≥11 points, respectively, with all-cause mortality and cardiovascular mortality, as well as with the total number of nonfatal cardiovascular events (CVEs) in Russia.Material and methods. The study included male and female population aged 25-64 years from the Epidemiology of Cardiovascular Diseases and their Risk Factors in Regions of Russian Federation (ESSE-RF) study who signed an informed consent. The study included 16941 people (men, 6811 (40,2%)). To assess the anxiety and depression, HADS scale was used. The statistical analysis included individuals with subclinical/clinical (HADS ≥8) and clinical (HADS ≥11) anxiety and depression (HADS-A and HADS-D). The median of prospective follow-up was 5,5 years (from 2012 to 2019). The composite endpoint (CE) (cardiovascular death and nonfatal CVE occurred in 268 (4,2%) men and 203 (2,1%) women, while all-cause — in 220 (3,2%) men and 152 (1,5%) women.Results. The results obtained showed that the survival rate of men and women with varying degrees of anxiety (HADS-A ≥8 and ≥11) was associated with all-cause mortality and CE in women. However, this relationship has not been confirmed in multivariate models. In the multivariate Cox proportional hazards model 1 (M1), a significant association of depression with all-cause mortality in women was revealed — HADS-D ≥8: relative risk (RR), 2,22; 95% confidence interval (CI): 1,56-3,15 and ≥11: RR, 2,43; 95% CI: 1,65-3,59 (p<0,005), as well as in men — HADS-D ≥8: RR, 1,51; 95% CI: 1,10-2,08 (p=0,01). In model 2 (M2), when added to M1 as a predictor of prior cardiovascular disease (≥3), depression was significantly associated with all-cause mortality only in women — HADS-D ≥8: RR, 2,23; 95% CI: 1,53-3,24 (p<0,005); HADS-D ≥11: RR, 2,61; 95% CI: 1,74-3,92 (p=0,01). In addition, only in women, subclinical/clinical depression (HADS-D ≥8) was significantly associated with fatal and non-fatal CVE — HADS-D ≥8: RR, 1,46; 95% CI: 1,08-1,98 (p=0,02).Conclusion. Depression (HADS-D ≥8 and ≥11) in Russian women was significantly associated with all-cause mortality and CE (HADS-D ≥8). In men, depression (HADS-D ≥8) was significantly associated with allcause mortality when only conventional risk factors were included in the model, without taking into account prior cardiovascular disease. Anxiety in multivariate models was not associated with all-cause mortality and CE in both sex groups.

Aim. To study the contribution of hypertension (HTN) to survival and mortality in the Russian population.Material and methods. This prospective observational cohort included representative samples from 11 Russian regions (men and women aged 25-64 years, n=18251) examined in 2012-2014 as part of the Epidemiology of Cardiovascular Diseases and their Risk Factors in Regions of Russian Federation (ESSE-RF) study. The examination included a questionnaire (12 modules), anthropometric and blood pressure (BP) measurements, as well as biochemical blood tests. HTN was considered aa a systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg, or when a subject receives antihypertensives. Treatment efficacy was considered as the proportion of persons (%) who achieved target BP among those taking antihypertensives. Depending on HTN status, all participants were divided into 4 groups: 1) those without HTN;2) those with HTN, taking antihypertensive agents and having systolic BP ≤140 mm H. and diastolic BP ≤90 mm Hg (effective therapy);3) those with HTN, taking medications, but not achieving target BP (ineffective therapy); 4) those with HTN, not taking antihypertensives. The life status of participants was updated every 2 years. Kaplan-Meier survival curves, as well as univariate and multivariate Cox proportional hazards models were created.Results. The presence of HTN significantly reduced survival (p<0,001) in the cohort, which is significant when adjusted for age (men — relative risk (RR)=1,47, p<0,001, women — RR=1,17, p<0,001). In the multivariate model, the male sex (RR=2,3 p<0,001), age increase, smoking, tachycardia, and HTN are significant for all-cause mortality only for men, but not for women. However, for women, absence of higher education was significant. The presence of HTN significantly worsens cardiovascular survival in both sexes (p<0,0001). HTN increases the risk of a composite endpoint for both men and women (p<0,001). Analysis of Kaplan-Meier curves showed the worst survival rate in persons with HTN, taking antihypertensive drugs, but not reaching target BP levels.Conclusion. The presence of HTN significantly worsens the survival rate of men and women. Special attention of medical community should be directed to increasing the proportion of effectively treated patients with HTN.