Antihypertensive Treatment Research Articles

Effect of antihypertensive drug classes in metabolic syndrome

Background: Metabolic syndrome (MetS) affects approximately 35% of the adult population of United States as well as categorized by the synchronized existence of hypertension, hyperglycemia, obesity and dyslipidemia. Now a days, this is the main cause of leading CVD (cardiovascular disease) risk in an individual. Raised blood pressure is the record common component of this syndrome and this incidence increases with age. Objective: This research was carried out to recommend the characterizations for the metabolic syndrome along with the occurrence of hypertension in this disorder. Additionally, indications concerning the properties of metabolic of the diverse antihypertensive drug modules and their consequence on metabolic syndrome will be demonstrated. Methods: A comprehensive trial in different patients were performed to identify data from clinical investigations for the occurrence, patho-physiology and treatment of hypertension in MetS. Results: Hypertension existing in almost 79% Pakistani patients alon with metabolic syndrome. The usage of thiazide diuretics, and beta-blockers salts, is dejected in the present community; though, latest signs recommend its use under precise circumstances. The Ca. channel inhibitors appear to apply a unbiased outcome on Metabolic syndrome. Whereas, renin angiotensin scheme inhibitors are supposed to be of the utmost advantage. Even though, variances occur among various agents of this class. Conclusion: Debate still exists about the ideal anti-hypertensive treatment in Metabolic syndrome. Due to the huge occurrence of hypertension in Pakistani community, still, further investigations and data is in dire need for this treatment.

Cost-Effectiveness of Salt Substitution and Antihypertensive Drug Treatment in Chinese Prehypertensive Adults.

Recent guidelines recommend antihypertensive drug treatment for prehypertensive individuals with blood pressure between 130/80 and 139/89 mm Hg. This study evaluates the cost-effectiveness of 3 interventions in Chinese prehypertensive adults: salt substitution, antihypertensive drug treatment, and their combination. We developed a Markov cohort model to estimate cardiovascular disease (CVD) events, costs, and quality-adjusted life years (QALYs) over a lifetime. Data from the China Kadoorie Biobank informed the simulation. Costs and utilities were drawn from published sources. We evaluated the cost-effectiveness of salt substitution alone, antihypertensive drug treatment alone, and a combination of the 2, focusing on the overall prehypertensive population, those at high CVD risk, and different starting ages (40, 50, 60, and 70 years). Incremental cost-effectiveness ratios (ICERs) were calculated per QALY gained. Salt substitution at age 40 years is the only cost-effective strategy for prehypertensive individuals, with an ICER of $6413.62/QALY. For those at high CVD risk, the combination intervention starting at age 40 years is most cost-effective, with an ICER of $2913.30/QALY. Interventions initiated at younger ages yielded greater CVD reductions and lower ICERs. For example, a combined intervention at age 40 years reduces CVD events by 5.3% with an ICER of $2913.30/QALY, compared with 4.9% and $32 635.33/QALY at age 70 years. These results were consistent across sensitivity analyses. In China, replacing usual salt with a salt substitute is more cost-effective than treating prehypertensive individuals over the age of 40 years with antihypertensive drugs. Furthermore, starting intervention at a younger age in prehypertensive adults can result in even greater cost savings.

Association of hypertension and the risk of cancer: a study based on the UK Biobank

Abstract Introduction With the increasing incidence rate of hypertension and carcinoma, there is a growing interest in investigating the potential link between these two diseases. The subdiscipline of hypertension, Onco-hypertension, has been proposed and attracted much attention. However, there are still few researches on this subdiscipline. Purpose This study aims to investigate the relationship between hypertension and the occurrence of cancer. Additionally, we explore whether anti-hypertensive treatment has any impact on the incidence of cancer. Methods This study involved 244,496 participants recruited between 2006-2010 from the UK Biobank, with 21,765 participants were diagnosed with the hypertension according to the ICD10 coding. The Cox regression was used to analyse the the risk of cancer associated with hypertension. The effect of anti-hypertensive treatment on the occur of cancer was also verified according to the Cox regression and the Drug target Mendelian randomization. Results Compared to those participants without hypertension, those people with hypertension have higher risk of the occur of cancer(adjusted hazard ratio(aHR) 1.35, 95% confidence interval(CI)1.3-1.4), especially in breast cancer(aHR 1.43, 95% CI 1.27-1.61), prostate cancer(aHR 1.85, 95% CI 1.7-2.02), lung cancer(aHR 2.15, 95% CI 1.86-2.48), renal cancer(aHR 1.91, 95% CI 1.46-2.49), pancreas cancer(aHR 1.55, 95% CI 1.2-2). Compared to those people with hypertension but without anti-hypertensive treatment, the anti-hypertensive treatment increase the cancer risk(aHR 1.19, 95% CI 1.06-1.33). However, thiazide diuretic have protect effect for hypertension patients on occur of the prostate cancer (aHR 0.74, 95% CI 0.61-0.89) and beta-receptor blocker have protect effect for hypertension patients on occur of the lung cancer (aHR 0.71, 95% CI 0.54-0.93). The result of Drug target Mendelian randomization shows the anti-hypertensive treatment have no significant effect on the risk of cancer. Conclusion The onset of high blood pressure is linked to an elevated risk of several cancers. However, it cannot be conclusively determined whether the use of medications for high blood pressure increases or decreases the overall risk of cancer. This study provides instructive evidences for the further study of Onco-hypertension.The result of main analyseThe analyse of the antihypertensive drug

Antihypertensive treatment of masked hypertension guided by ambulatory blood pressure monitoring: a double-blind, placebo-controlled trial

Abstract Background Masked hypertension, office normotension combined with out-of-office hypertension, is associated with target organ damage (TOD), but whether antihypertensive treatment guided by out-of-office blood pressure (BP) would reduce TOD is unproven. Purpose To assess TOD change on antihypertensive treatment guided by ambulatory BP monitoring. Methods We conducted a double-blind, placebo-controlled randomized trial at 15 Chinese hospitals. Enrolment started on February 14, 2017 and follow-up ended on October 31, 2021. Patients of either sex, aged 30-70 years, not on antihypertensive drugs were eligible, if at two screening visits 1-week apart office BP was <140/<90 mm Hg and the 24 hour, daytime or nighttime ambulatory BP was ≥130/≥80, ≥135/≥85, or ≥120/≥70 mm Hg, respectively. Patients had ≥1 sign of TOD: ECG left ventricular hypertrophy (LVH), brachial-ankle pulse wave velocity (baPWV) ≥1400 cm/s, or urinary albumin-to-creatinine ratio (ACR) ≥3.5 mg/mmol in women and ≥2.5 mg/mmol in men. Active antihypertensive treatment consisted of allisartan starting at 80 mg/day to be increased to 160 mg/day at month 2 and to be combined with amlodipine 2.5 mg/day at month 4, if the ambulatory BP remained uncontrolled. Matching placebos were used likewise in the control group. The primary endpoint included normalization of baPWV, ACR or LVH or ≥20% reduction in baPWV or ACR. Results Of 320 patients (43.1% women; mean age 54 years), 153 were randomized to active antihypertensive treatment and 167 to placebo. At baseline, office BP averaged 130/81 mm Hg and the 24 hour BP 136/84 mm Hg. The prevalence of elevated baPWV, ACR and LVH was 97.5%, 12.5%, and 7.8%. The 24-hour systolic/diastolic decreased by 9.0/5.6 mm Hg (95% CI: 7.5-10.5/4.8-6.5 mm Hg) on active treatment and by 1.4/1.0 mm Hg (-0.1-2.8/0.2-1.8 mm Hg) on placebo. Regression of TOD, the primary outcome, occurred more frequently in patients randomized to active treatment than in those assigned to placebo with 1 year rate of 45.8% (95% CI: 37.9-53.7%) and 25.8% (19.1-32.4%), respectively (P<.001 for between-group differences in BP and TOD). Per-protocol and subgroup analyses were confirmatory. Conclusions Masked hypertensive patients require antihypertensive treatment guided by out-of-office BP monitoring before subclinical TOD progresses to major cardiovascular complications.

Unleashing the potential: early evaluation of blood pressure control with novel measurements in patients with hypertension

Abstract Objective To assess the prognostic value of two novel blood pressure measurements——short-term cumulative systolic blood pressure (SBP) load and Time in Target Rang (TTR) in major adverse cardiovascular outcomes and all-cause mortality. Method This is a post-hoc analysis of the SPIRNT (Systolic Blood Pressure Intervention Trial). Participants with complete record of BP values and no adverse events occurred in the initial 90-days follow-up were enrolled. Short-term cumulative SBP load and TTR were calculated by the 3-month SBP values in the follow-up period (Fig 1). The primary outcome was major adverse cardiovascular events (MACEs), defined as the composite of myocardial infarction, stroke, heart failure and cardiovascular death. Secondary outcomes were the components of the primary outcomes and all-cause mortality. Results The study population included 8639 adults (median [IQR]or mean (%) baseline age, 67 [61,76] years; 2940 women (35.1%); Median follow-up time 3.8[3.3-4.4] years). 559 MACEs were occurred. Participants categorized by tertiles of cumulative SBP Load (T1: [0,0.1572]; T2: (0.1572 ,3.5946]; T3: (3.5946 ,30.2949]) showed a significant increase hierarchical trend (P for trend <0.05) in the incidence of MACEs and stroke. For Participants grouped by SBP TTR (T1: [0,21.2657]; T2: (21.2657 ,71.1462]; T3: (71.1462 ,100]), it indicated a decrease hierarchical trend (P for trend <0.05) in the incidence of MACEs and MI (Fig2 and Fig3). Both short-term cumulative SBP Load (HR: 1.117(1.033-1.208)) and TTR (HR: 0.861(0.785-0.945)) were correlated with MACEs independently(tabal1). According to C-statistics and Net Reclassification Indexes (NRI), short-term cumulative SBP Load and TTR both outperformed mean SBP and SBP standard derivation (SD) on the prognosis value of MACEs. Moreover, our results showed that the coefficient of cumulative SBP Load under penalty decreased to 0 with the largest log(lambda),which indicted a major role across 4 different measures in models. (Fig 4). Conclusions Both short-term cumulative SBP load and TTR had an independent prognosis value for MACEs superior to mean SBP and SBP SD in hypertension patients without diabetes. This study provided the evidence of novel BP measurements for early assessment of BP levels after antihypertensive treatment.

Higher systolic blood pressure in left not right upper limb is associated with all-cause mortality risk in a community-based population

Abstract Background and Purpose Previous studies have shown that elevated inter-arm systolic blood pressure difference (SBPD) is a valuable indicator for assessing the risk of all-cause mortality. However, no research currently reports that the different impact of higher SBP in which upper limb on all-cause mortality risk. This study investigates which side of the upper limbs has a higher SBP that is more associated with all-cause mortality risk in a community population. Methods The subjects were from the a Atherosclerosis Cohort of the Department of Cardiology of our University First Hospital from 2012 to 2021, and those with missing data of brachial-ankle pulse wave velocity and a history of myocardial infarction or stroke in the baseline survey were excluded. The endpoint was defined as all-cause mortality. SBPD was defined as the difference between the systolic blood pressure of the right arm minus the systolic blood pressure of the left arm by the noninvasive arteriosclerosis detection device BP-203RPEIII (Omron, Japan). SBPD was categorized into four groups: 0-10 mmHg (right arm higher <10mmHg), ≥ 10 mmHg (right arm higher ≥ 10 mmHg ), -10 to < 0 mmHg (left arm higher ≤10 mmHg), and < -10 mmHg (left higher > 10mmHg). The relationship between SBPD and all-cause mortality risk was determined by multivariable Cox proportional hazards regression after adjusting for covariates (age, body mass index, gender, current smoking, current drinking, estimated glomerular filtration rate, diabetes, hypoglycemic treatment, total cholesterol, triglycerides, lipid-lowering treatment, and antihypertensive treatment). Results Totally, 8628 participants were included, with a mean age of 56.58 ± 8.97 years old, and 64.51% (5566) were female. Among them, 380 (4.40%) had an SBPD ≥ 10 mmHg, and 409 (4.74%) had an SBPD < -10 mmHg. During a median follow-up of 9.87 years, 442 cases of all-cause mortality (5.19%) occurred. The Kaplan-Meier curve suggested that the greater the difference in SBPD, the higher the cumulative risk of all-cause mortality. The Log-rank test showed a significant statistical difference (P= 0.0115). Compared to right arm higher <10mmHg group, the risk of all-cause mortality was not significantly elevated in right arm higher ≥ 10 mmHg (adjusted HR=1.17, 95% CI: 0.74-1.84, P=0.507) or left arm higher ≤10 mmHg group (adjusted HR=0.90, 95%CI: 0.74-1.11, P=0.329). However, the risk of all-cause mortality significantly increased by 59% in left higher > 10mmHg Group (adjusted HR=1.59, 95% CI: 1.10-2.30, P=0.013). The results remained significant after adjusting for peripheral right arm SBP (adjusted HR=1.56, 95% CI: 1.08-2.24, P=0.018). Conclusion This study found that a higher SBP in the left arm is associated with a higher risk of all-cause mortality in a Beijing community-based population, and they should be monitored and intervened more intensively.Hazard Ratios for all-cause mortalitySurvival curves for SBPD groups

Antihypertensive treatment during pregnancy and maternal and fetal outcomes

Abstract Introduction Arterial hypertension affects about 5-10% of pregnancies and has detrimental effects on pregnancy outcomes in both the mother and fetus. The study aimed to analyse the outcomes of pregnancy in women treated for arterial hypertension in pregnancy in the Czech Republic. Methodology Nationwide data on all births and abortions in the period 2012-2022 in the Czech Republic were obtained from the National Registry of Reproductive Health (NRRZ) and the National Registry of Reimbursable Health Services (NRHZS). Women who had the diagnosis I10 within one year before pregnancy and were prescribed any antihypertensive drug from selected ATC groups (C02, C03, C07, C08, C09) were classified as pre-existing hypertension. Women diagnosed with O13 or I10 during pregnancy were classified as pregnancy induced hypertension. Hypoxia in the new-born was defined as pH <7.1 or Apgar score <8 present after delivery. For all factors, univariate logistic regression was used to calculate the odds ratios (OR) of adverse outcomes. Results There were total of 1,154,648 deliveries in the 11-year period. 95,215 women had hypertension in pregnancy, out of these 21,094 (22.2%) were treated with antihypertensive drugs. Odds ratios for caesarean section, pre-term delivery, low birth weight, new-born hypoxia and pre-eclampsia in women using different antihypertensive classes and drugs are shown in the Table. Risk of maternal and fetal complications was found to be higher with calcium channel blockers (mainly amlodipine) compared to methyldopa and beta blockers. Among beta blockers, bisoprolol had the most favourable safety profile. Although used in limited numbers, diuretics, verapamil, ACE-inhibitors and angiotensin receptor blockers (ARBs) appeared to be comparably safe to methyldopa. Combination of multiple antihypertensive drugs was associated with higher risk of adverse outcomes. Conclusion Bisoprolol, verapamil and diuretics seem to have the risk of adverse maternal and fetal outcomes comparable to methyldopa. Amlodipine and multiple antihypertensive drug combinations are associated with increased risk.Table

Prevalence and prediction of masked uncontrolled hypertension in patients recently hospitalised for an acute coronary syndrome

Abstract Background Masked uncontrolled hypertension (MUCH) is defined as normal office blood pressure (BP) but elevated out-of-office BP in patients on antihypertensive treatment. MUCH is associated with similar cardiovascular risk as sustained hypertension and is clinically challenging since this often remains undetected without out-of-office BP measurements. Purpose To study the prevalence of MUCH following an acute coronary syndrome and to utilise machine learning methods to develop prediction models for identifying MUCH. Methods Ambulatory 24-h BP measurement (ABPM) was performed in 100 patients attending the cardiology outpatient clinic at a Swedish university hospital following an acute coronary syndrome, as part of a study which screened for co-morbidities. From the SWEDEHEART registry, 106 variables during the hospital care period and subsequent follow-up visit (after 6-10 weeks) were pre-processed including filtering on 5 or more missing values and zero or near-zero variance. Variable importance for the prediction of MUCH (office BP < 140/90 mm Hg at ABPM start but mean 24-h BP ≥ 130/80 mm Hg) was assessed using the Boruta and least absolute shrinkage and selection operator (LASSO) machine learning algorithms. Subsequently, logistic regression, LASSO and random forest models using different variable subsets were evaluated by receiver operating characteristic area under the curve (AUC) in repeated cross-validation. Results Age was 62.0±8.4 years, 74% male, 54% had NSTEMI and 46% STEMI. The follow-up visit and ABPM were performed at median 7 and 11 weeks, respectively, after hospital discharge. Among 90 patients with complete data and ABPM recordings, 31 had mean 24-h BP above target levels, of which 18 were identified with MUCH. Patients with MUCH had lower eGFR (68±11 vs 76±12 ml/min/1.73m², P=0.009), and more often a history of hypertension (89 vs 53%, P=0.005) and diabetes mellitus (44 vs 11%, P=0.003). In total, 65 variables where eligible for machine learning after filtering. Boruta and LASSO identified pulse pressure at the follow-up visit, serum creatinine, diabetes mellitus and history of hypertension as important predictors. Random forest, logistic regression and LASSO showed mean AUC 0.826, 0.822, and 822, respectively, in cross validation using these predictors. Conclusions In this small trial, one in five had MUCH at follow-up after an acute coronary syndrome, which highlights the importance of out-of-office BP measurements. The easily accessible measures of pulse pressure at the follow-up visit, serum creatinine, diabetes mellitus and history of hypertension were identified as important predictors of MUCH. A simple prediction model may be used as a clinical decision support tool after appropriate external validation.

10 years after treatment with renal denervation of the sympathetic nerves for resistant hypertension: what happened to the patients and their office blood pressure? An observational study

Abstract Background Catheter-based renal denervation of the sympathetic nerves (RDN) for resistant hypertension has long been controversial. A renewed clinical and scientific interest in defining the appropriate role of RDN in the treatment of resistant hypertension has become evident in recent years. The efficacy and safety of RDN treatment is mainly based on available data up to three years, whereas data concerning the long-term effect and safety are scarce. Purpose We therefore wanted to investigate the long time change in blood pressure (BP) in patients treated with RDN for resistant hypertension. Methods A review of data from the electronic patient journal concerning all RDN treated patients was initiated and completed in October 2023. Every registration of an office BP listed in the patient file, antihypertensive treatment, cardiovascular events, and renal function between 2012 and 2023 were registered. For each patient the average of all office post RDN blood were averaged for every year and for their complete follow-up. The outcome in blood pressure was the change in BP from baseline pre RDN office to follow-up Results Between January 2012 and October 2013, 19 consecutive patients underwent RDN treatment, 10 men and 9 women with a median age of 63 years (range 35-74 years). At baseline the median systolic office BP was 181 mmHg (range 162–230 mmHg) and the diastolic office BP 97 mmHg (range 82-123 mmHg) on a median of 5 (range 0-7 ) antihypertensive drugs. During follow-up the number of antihypertensive drugs were reduced in 7, unchanged in 10, and increased in 2 patients. Two patients left the outpatient clinic with normal BP after 2 years. Two patients developed heart failure after 7 years and were censored at that time-point. 15 (79%) patients had office BP recorded up to 9 or 10 years. In the 15 (79%) patients with available office BP 9 to 10 years after RDN the median systolic and diastolic office BPs were reduced by 39 mmHg (range -2 to - 66 mmHg) and 18 mmHg (range -11 to - 55 mmHg) respectively, relative reduction 22% (range 5-36%) and 20% (range 6-32), respectively. Conclusion During a follow-up of 9 to 10 years after RDN without a step-up in antihypertensive medication a relative decrease of ~20% in systolic and diastolic BP was observed.

Masked hypertension is highly prevalent among patients with high-normal office blood pressure - based on the results of the Hungarian ABPM Registry

Abstract Background Current European guidelines recommend initiating antihypertensive treatment for patients with high-normal office blood pressure (HNOBP) if their cardiovascular (CV) risk is very high.1 Ambulatory blood pressure monitoring (ABPM) is a recommended tool to identify whitecoat- (WCH) and masked hypertension (MH), and both conditions can be present in patients with HNOBP. Purpose The purpose of our study was to assess the prevalence of white-coat and masked hypertension in patients with HNOBP, the proportion of very high CV risk, and to identify the predictors of WCH and MH. Methods We collected data from the Hungarian ABPM Registry, which is an ongoing, multicenter, open-label, observational study including 38720 adult patients. ABPMs were performed with validated Meditech ABPM-06 monitors. We analyzed the ABPM curves of 4389 HNOBP patients. In the diagnosis of hypertension, 24 hour-, daytime- and nighttime mean BP values were each considered separately. OBP measurements and ABPMs were performed by GPs, internists and cardiologists. 89 patients were excluded due to missing data. Results ABPM recordings confirmed MH in 67.4%(n=2899) of the cases, while WCH in 15.3%(n=659). In 17.3%(n=742) BP was in HN category both in the office and with ABPM (apparent high-normal blood pressure /appHNBP/). WCH patients (57.11±17.47) were older, than appHNBP (54.54±16.9), and MH patients (53.38±16.70)(p<0.001). WCH (19.4%, n=489) and appHNBP (19.4%, n=488) were more frequent among females, than in males (14.3%, n=254; 9.6%, n=170, respectively, p<0.001). However, MH was more prevalent in males compared to females (76.2%(n=1355) vs 61.2%(n=1544), respectively, p<0.001). Snoring, obesity and diabetes mellitus were more frequent in MH than in appHNBP and WHC patients (Snoring: 30.6%(n=887) vs. 25.7%(n=191) vs. 20.8%(n=137), p<0.001; Obesity: 22.9%(n=663) vs. 16.0%(n=119) vs. 13.4%(n=88), p<0.001;Diabetes mellitus: 12.1%(n=350) vs. 8.9%(n=66) vs. 9.9%(n=65), respectively, p=0.025). Independent predictors of WCH were age (OR=1.01[1.003;1.02]), female sex (OR=1.50[1.19;1.89]) and snoring (OR=0.76[0.59;0.97]). Independent predictors of MH were male sex (OR=1.69[1.43;2.00]), snoring (OR=1.27[1.06;1.53]) and obesity (OR=1.55[1.25;1.92]). 76% of all patients received antihypertensive treatment irrespective of the BP groups (WCH: 76.2%(n=502), appHNBP: 76.3%(n=566), MH: 76.5%(n=2217), p=NS). 11.7%(n=502) of all patients had very high CV risk and only 2.5%(n=25) did not receive antihypertensive treatment. Similar results were found among WCH, appHNBP and MH patients (very high CV risk: 13.8%(n=91) vs. 11.2%(n=83) vs.11.7%(n=328), p=NS; no treatment: 1.9%(n=3) vs. 1.7%(n=3) vs. 2.8%(n=19), p=NS). Conclusions In patients with HNOBP, MH is highly prevalent. MH might be suspected in young, obese, male patients with diabetes mellitus and snoring. WCH was more frequent in older females. Based on our data, the majority of patients with HNOBP and very high CV risk are treated.

A higher adherence to perindopril-based anti-hypertensive therapy is associated with a reduced risk of cardiovascular outcomes and all-cause mortality in real clinical practice in Italy

Abstract Background Therapeutic management of hypertension is a landmark of cardiovascular (CV) risk prevention. Combined therapies with at least 2 anti-hypertensive agents are required in many patients in whom monotherapy and lifestyle interventions failed in blood pressure control. It is well-known that poor medication adherence remains a major barrier to achieving the therapeutic targets for all CV drugs, including anti-hypertensives. Purpose We evaluated the relationship between adherence to perindopril (PER)-based therapeutic regimen prescribed as single-pill combination (SPC) or free-pill and CV outcomes and all-cause mortality in a large Italian population. Methods A retrospective analysis was performed using administrative databases corresponding to around 6.7 million health-assisted residents. Hypertensive adults were first identified through hospitalization discharge diagnosis or exemption codes for hypertension between 2010 and 2021. Patients prescribed PER-based therapies were screened for all combinations of PER with amlodipine (AML) and/or indapamide (IND) (all formulations, single-pill or free-pill). Time of the first prescription of a PER-based regimen during the inclusion period was considered the index-date. The analysis included all hypertensive subjects prescribed a PER-based therapy, having available data at least 12 months before and 24 months after the index-date, respectively. Since the analysis was focused on the possible associations between adherence level and CV outcomes and all-cause mortality, adherence was assessed during the first year of follow-up on alive patients and outcomes were assessed during the second year. Adherence was assessed using the proportion of days covered (PDC) approach on 1-year follow-up, and considering a PDC<80% as poor-to-moderate adherence, and PDC ≥80% as good adherence. The Cox’s proportional hazard model was applied to estimate Hazard Ratio (HR) adjusting for baseline covariates, including comorbidity profile and pill burden. Results The included cohort (N=24,476) was divided into sub-groups according to adherence in poor-to-moderate (N=6,781) and good adherent patients (N=17,695) with a mean age of 64.8±13.3 and 64.6±11.9 years old, respectively. The Cox’s proportional hazard model showed that good adherence was associated with a relative risk reduction of 23% in all-cause mortality (Table 1A), 21% in all CV events (Table 1B), 17% in ischemic heart disease (Table 1C), 33% in cerebrovascular events (Table 1E), and 22% in the composite outcome of CV events/all-cause mortality (Table 1G). Conclusions The present analysis provided evidence from the Italian real clinical practice that good adherence to PER-based anti-hypertensive therapy results in significantly lower cardiovascular risk and all-cause mortality. These data further emphasize the importance of promoting cost-effective measures to increase medication adherence in patients on anti-hypertensive treatment.

Blood pressure polygenic risk scores associate with resistant hypertension in individuals with type 1 diabetes

Abstract Background Hypertension is a major risk factor of global disease burden, but treatment goals are often not met. A subset of individuals with hypertension is affected by treatment-resistant hypertension (RHTN), and they suffer from increased cardiovascular morbidity and mortality. Early identification of individuals at risk of RHTN could lead to more efficient antihypertensive drug treatment. Purpose The aim of this study was to investigate whether polygenic risk scores (PRS) for systolic (SBP) and diastolic blood pressure (DBP) predict RHTN in individuals with or without type 1 diabetes (T1D). Methods We performed association analyses between PRSs and RHTN in two Finnish cohorts: The Finnish Diabetic Nephropathy Study (FinnDiane) and the Finnish individuals of the LIFE Study (LIFE-Fin). FinnDiane is an ongoing, observational nationwide study aiming to identify genetic and clinical risk factors for complications of T1D. We included data from 778 adults (476 with RHTN and 302 with controlled hypertension). LIFE is a randomized, double-blind study evaluating long-term effects of losartan compared with atenolol in patients with signs of left ventricular hypertrophy. We used SBP and DBP data from 378 Finnish individuals (173 with RHTN and 205 with controlled hypertension) at the four-year visit of the study. In FinnDiane, RHTN was defined as SBP ≥130 or DBP ≥85 mmHg and the use of three or more antihypertensive drugs, or SBP <130 and DBP <85 mmHg and the use of four or more antihypertensive drugs. In LIFE-Fin, RHTN was defined as SBP ≥140 or DBP ≥90 mmHg and the use of three or more antihypertensive drugs. Controlled hypertension was defined as the use of three or fewer antihypertensive drugs and SBP <130 and DBP <85 mmHg in FinnDiane, and as SBP <140 and DBP <90 mmHg in LIFE-Fin. We calculated a PRS for each participant using genome-wide association study data for 1,098,015 genetic variants; the variant-specific data were derived from UK Biobank based PRS-CS-method computed PRSs (1). Results We observed significant associations of SBP and DBP PRSs with RHTN in FinnDiane (OR 1.56 [1.30; 1.87], P = 1.8e-6, and OR 1.25 [1.04; 1.50], P = 0.02, per one-SD increase of the PRS value) when adjusted for age, sex, estimated glomerular filtration rate and body mass index. The association between SBP PRS and RHTN remained significant when T1D individuals with or without albuminuria were analysed separately. Neither SBP nor DBP PRSs were significantly associated with RHTN in LIFE-Fin. Conclusion Higher SBP PRSs associate with higher risk of RHTN in individuals with T1D, with or without albuminuria, but not in nondiabetic individuals with hypertension. It remains to be investigated whether general blood pressure genetics contribute to RHTN in the general population.

What characterizes normotensive individuals with obesity and normal systolic heart function? A descriptive study from the SCAPIS cohort

Abstract Background Heart failure and cardiovascular disease are strongly related to obesity, and the incidence of these conditions shows a linear relationship with increasing body mass index (BMI). Despite these known facts, some individuals with obesity show no clinical signs of heart disease or arterial hypertension (AH). Purpose We aimed to investigate the characteristics of individuals with obesity without impaired left ventricular function and left ventricular hypertrophy (termed systolic heart function, SHF) and AH, compared to individuals with obesity with signs of impaired SHF or AH, and individuals without obesity with and without signs of impaired SHF or AH. Method A cross-sectional analysis was performed of the 4,692 individuals who had undergone a transthoracic echocardiography within the Swedish CArdioPulmonary bioImage Study (SCAPIS). Participants were divided into four groups: 1) individuals with obesity (BMI³30 kg/m2) without impaired SHF (normal left ventricular systolic function and left ventricular mass) and no AH (based upon the absence of antihypertensive treatment) (ObSHF/AH-, n=623; 13%), 2) individuals with obesity with impaired SHF or AH (ObSHF/AH+, n=252; 5%), 3) individuals without obesity and without impaired SHF and no AH (NObSHF/AH-, n=3179; 68%) and 4) individuals without obesity with impaired left ventricular systolic function, left ventricular hypertrophy or AH (NObSHF/AH+, n=638; 14%). Individuals in group 1 (ObSHF/AH-;) were compared to those in groups 2-4 through descriptive analyses. Results Compared to ObSHF/AH+ individuals, ObSHF/AH- subjects showed significantly lower HbA1c (p<0.001), fasting plasma glucose (p<0.001), triglyceride (p<0.001), NT-proBNP (p=0.035) and troponin I (p<0.001) levels. Furthermore, no significant differences between the two obese groups could be seen regarding BMI (p=0.074), whereas waist-to-hip ratio was lower in ObSHF/AH- subjects (p<0.001). ObSHF/AH- individuals had higher glucose and lipid levels as well as higher blood pressure than individuals without obesity. Interestingly, no differences were seen between ObSHF/AH- and NObSHF/AF- subjects regarding NT-proBNP (p=0.864) and troponin I levels (p=0.110). Furthermore, left ventricular mass index (LVMI) was significantly higher in ObSHF/AH- subjects compared to NObSHF/AH- individuals (73.8 vs. 72.1 g/m2, p=0.015) and the ejection fraction was significantly lower (57.4 vs. 59.6 %, p<0.001). Conclusion When ObSHF/AH- and NObSHF/AH- subjects were compared, markers of cardiac damage/remodeling did not differ significantly, indicating that heart function might be preserved despite a worsened metabolic profile and an obese phenotype, through putative protective mechanisms yet to be explored. However, parameters of SHF were unfavorable for ObSHF/AH- when compared to NObSHF/AH-, further implicating preclinical cardiac impairment in individuals with obesity.

Home blood pressure control and prescribing patterns of anti-hypertensive medications in a home blood pressure-based hypertension-specialized clinic in Japan: a sub-analysis of the Ohasama study.

Although the benefits of anti-hypertensive treatment are well known, the proportion of hypertensive patients with controlled blood pressure (BP) remains suboptimal. The present study aimed to compare BP control conditions in a hypertension-specialized clinic and non-hypertension-specialized clinics. This cross-sectional study used data from 379 treated patients who measured home BP in the Ohasama study between 2016 and 2019 (men: 43.0%, age: 71.6 years). Of those, 172 patients were managed at the hypertension-specialized clinic where physicians distributed home BP devices to each patient, evaluated the home BP data, and adjusted medications to maintain home BP values according to the recent Japanese guidelines. When we set morning home systolic/diastolic BP of <135/ < 85 mmHg as controlled BP, 93.6% of patients fulfilled the controlled home BP range, compared to 43.0% in non-specialized clinics (n = 207). The proportion of the patients with home morning BP < 125/ < 75 mmHg was 73.3% in the hypertension-specialized clinic and 20.8% in the non-hypertension-specialized clinics. Hypertension-specialized clinics prescribed three or more anti-hypertensive drug classes to 41.9% of patients, compared to 15.2% in non-specialized clinics. In the hypertension-specialized clinic, angiotensin II receptor blockers were most commonly prescribed (86.6%), followed by dihydropyridine calcium channel blockers (77.9%), thiazide (including thiazide-like) diuretics (30.2%), mineralocorticoid receptor blockers (23.8%), and beta- and alpha-beta blockers (10.5%). In conclusion, the proportion of patients with controlled home BP was excellent in the hypertension-specialized clinic. Home BP-based hypertension practices, as recommended in the current Japanese guidelines, may be the key to achieving sufficient BP control.

Comparative insights into type non-A non-B vs type B acute aortic syndromes and their blood pressure management: a monocentric, retrospective, 11-year study

Abstract Background Acute aortic syndromes (AAS) are classified either as type A, if the ascending aorta is involved, or as type B, if only the descending aorta is; AAS affecting the aortic arch, alone or in combination with the descending aorta, have recently been classified as type non-A-non-B (NANB). Few and discordant data are available about the differences between type B and type NANB AAS, especially in terms of presentation, management and prognosis. Little evidence also exists about the effects of blood pressure (BP) management, peaks and variability on in-hospital outcomes in such context. In particular, the largest international AAS registry suggests a comparable course and prognosis, while a recent meta-analysis indicates a poorer clinical outcome with higher rate of complications, need of invasive treatment and mortality in the case of type NANB AAS. Methods We conducted a monocentric, observational, analytical, retrospective registry study including all patients ≥ 18 years old admitted to our tertiary referral hospital with a diagnosis of type B or type NANB AAS from January 2011 to December 2021. Epidemiological, clinical, operative and outcome data were analyzed by comparing type B and type NANB AAS patients. We also focused on systolic and diastolic BP, in terms of both peak values as well as BP variability (BPV); BPV was defined as the difference between the peak and the through value on a certain day. Blood pressure variables were analyzed in relationship with mortality and the failure of an initial conservative management. Results 274 type B and 44 type NANB AAS patients were enrolled. The only significant differences between the two groups were a higher rate of pre-operative complications in type NANB patients (p=0.002) resulting in a higher rate of invasive management (p=0.005), particularly as failure of an initial conservative strategy (p=0.018). However, comparable rates of post-operative complications and in-hospital mortality (overall 7%) were observed. In the overall population, lower limb ischemia, ST segment depression, and post-operative visceral ischemia were associated with higher in-hospital mortality. Peri-aortic effusion was independently associated with failure of conservative management, whereas diagnosis of intramural hematoma (as opposed to other subtypes of AAS) appeared to be protective. Among all BP variables (including anti-hypertensive treatment intensity and daily systolic or diastolic BP peaks and variability), only peak systolic BP on day 5 was found to be non-independently associated with a higher risk of in-hospital mortality and failure of an initially conservative strategy. Conclusions In our study type NANB AAS were more often complicated and treated invasively than type B AAS, while having the same rates of post-operative complications and overall mortality. BP peaks had only a minor effect on outcomes, while BPV and BP management intensity did not have any significant impact.OutcomesBlood Pressure

Patient reported outcomes, control of hypertension and dyslipidemia: results of two epidemiological studies in Romania, conducted during pandemia (Snapshot-1) and post-pandemic (Snapshot-2)

Abstract Background Coexistence of hypertension and dyslipidemia is commonly found in daily practice. Patient reported outcomes (PRO) are increasingly used to guide clinical decision-making, as well as public reporting of health system performance. Purpose To assess patient reported outcomes (PRO: socio-economic factors, depression level, and treatment adherence) and control of blood pressure (BP) and LDL-cholesterol (LDL-C) during pandemia and in the post-pandemic period. Methods Two real-world, cross-sectional, multicentre, observational studies, with a similar design, were conducted in Romania during pandemia, in June 2021 (SnapShot-1), and post-pandemic, in June 2022 (SnapShot-2). They included 5004 consecutive outpatients diagnosed with both hypertension and dyslipidemia, addressing cardiologists, diabetologists, and general practitioners: 2469 in SnapShot-1 and 2535 in SnapShot-2. Patients completed a three-part questionnaire including: (1) questions on socio-economic factors; (2) Patient Health Questionnaire (PHQ-9) (Depression scale); and (3) Hill-Bone Medication Adherence Scale (HBMAS) for hypertension and dyslipidemia. Results Characteristics of patients were similar between studies: 65.0±10.0 years and 40.9% men (SnapShot-1), 63.6±10.7 years and 43.3% men (SnapShot-2). Most of the patients declared themselves as "adherent" to the prescribed treatment: 91.8% (SnapShot-1) and 93.0% (SnapShot-2) adherent to antihypertensive treatment; 89.6% (SnapShot-1) and 90.9% (SnapShot-2) adherent to lipid lowering treatment. Socio-economic factors were similar between studies, except education, with higher education rates in SnapShot-2 (Table 1). Compared to SnapShot-1, depression scores evaluated by PHQ-9 scale were lower in SnapShot-2, conducted post-pandemic: 5.9±4.9 for SnapShot-1, suggesting a "mild" depression level, vs. 4.9±4.6 for SnapShot-2, which is below the "mild" depression threshold. Similarly, the adherence scores measured by HBMAS were lower in SnapShot-1 vs. SnapShot-2: 33.8±3.0 vs. 34.0±2.9 for antihypertensive medication, and 33.5±3.5 vs. 33.7±3.4 for lipid lowering treatment (Table 2). Conclusion Data collected from two large epidemiological studies in Romania showed an improvement of post-pandemic depression rates, as well as an improvement of adherence scores. Use of PRO assessment in routine clinical practice could support identification of patients on risk for uncontrolled BP or LDL-C, in need of more intense medical care.

Arterial hypertension in the era of obesity bias: the impact of obesity status on pharmacological treatment intensification in patients with diabetes

Abstract Background Obesity is recognized as a significant risk factor for several chronic conditions, such as diabetes and hypertension. Despite the growing healthcare needs of individuals with obesity, they often encounter obesity bias, potentially impacting the quality of medical care they receive. Purpose The aim of this study was to explore the impact of obesity on the appropriateness of antihypertensive treatment decisions in individuals with concurrent diabetes and hypertension. Methods In this multicenter cross-sectional study, patients with type 2 diabetes and arterial hypertension who were receiving outpatient care across four centers in Southern Brazil were enrolled. Participants were categorized into two groups based on their Body Mass Index (BMI): eutrophic (BMI &amp;lt;25.0 kg/m²) and patients with obesity (BMI ≥30.0 kg/m²). The primary outcome evaluated was the difference in pharmacological treatment decisions for hypertension between groups, considering individualized hypertension targets from American Diabetes Association (ADA), European Society of Hypertension (ESH), and European Society of Cardiology (ESC). Analysis was conducted on whether patients failed to receive necessary treatment intensification, comparing groups through multivariable logistic regression. Results The study comprised 204 individuals with type 2 diabetes and arterial hypertension, including 53 eutrophic and 151 patients with obesity. It was observed that patients with obesity more frequently fail to receive appropriate treatment intensification when compared to eutrophic individuals. This finding was statistically significant across the hypertension targets set by the ESH (adjusted Odds Ratio [OR] 2.03 [95% Confidence Interval [CI] 1.08-3.83], p = 0.022), ESC (adjusted OR 1.94 [95% CI 1.03-3.65], p = 0.035), and ADA (adjusted OR 2.01 [95% CI 1.07-3.79], p = 0.021). Conclusion The study indicates that obesity may contribute to disparities in the management of hypertension, suggesting a link between obesity status and therapeutic inertia in treating arterial hypertension among these patients.

Adherence to anti-hypertensive therapy with perindopril-based single-pill versus free-pill combinations: a 10-year real-world analysis in Italy

Abstract Background/Introduction Despite the growing availability of blood pressure-lowering drugs, hypertension remains poorly controlled and a significant mortality cause worldwide. The silent course of the disease, suboptimal adherence, and complexity of therapeutic schedules are important factors in reducing the effectiveness of anti-hypertensive treatments at the population level. With the purpose of simplifying patients’ medication self-management, guidelines have strongly endorsed the use of anti-hypertensive therapy with single-pill combinations (SPCs). Perindopril (PER)-based SPCs, including both two- and three-drug combinations, have been available since 2008. Purpose We explored treatment adherence over 10 years in patients receiving PER-based regimens (SPC or free-pill combination) in Italy. Methods A retrospective real-world analysis was conducted on administrative databases covering 6.7 million Italian health-assisted residents. Among adults with hospitalization discharge diagnosis or exemption code for hypertension between 2010 and 2021, those with PER-based prescriptions were identified, considering combinations with amlodipine (AML) and/or indapamide (IND), either as SPC or free-pill or mixed (SPC+separate pill). The index-date (ID) was that of the first prescription of a PER-based regimen throughout the inclusion period. All patients with at least 12 months of available data before and after the ID were included. A cross-sectional analysis evaluated the yearly adherence for the period 2012-2021, calculating the proportion of days covered (PDC) by drug prescriptions on 1-year follow-up (PDC≥80% indicated high-adherence). Results Over 2012-2021, of 121,397 patients on a PER-based therapy, those treated with SPC ranged from 87% (during 2012) to 94.4% (during 2021), while free-pill and SPC+separate pill cohorts represented, respectively, 10.6-3.5% and 2.4-2.1% of all hypertensive patients. Over the decade, the proportion of adherent patients in SPC users was markedly higher than in free-pill and SPC+separate pill cohorts (Fig. 1). The sudden reduction of adherent patients during 2018-2019 was possibly due to a temporary shortage of PER/AML/IND as SPC in Italy from Nov-2018 to Mar-2019. Multivariate analysis showed that over 2012-2021 decade, free-pill and SPC+separate pill regimens resulted in significantly lower adherence (more than 80% reduction) than SPC formulation, while male gender and older age were predictive of better adherence (Table 1). Conclusions These findings from real clinical practice in Italy highlighted a growing attitude from clinicians to prescribe more manageable anti-hypertensive schemes based on SPC formulations, in line with current guidelines. The higher proportion of adherent patients among the users of PER-based SPCs corroborates the importance of alleviating pill burden, that is a key component in blood pressure control, and so in the reduction of hypertensive complications and cardiovascular risk.

Real-world analysis exploring the association between anti-hypertensive therapy with perindopril-based single-pill combinations (SPC) and cardiovascular outcomes and all-cause mortality in Italy

Abstract Background/Introduction A combination of blood pressure (BP)-lowering medications is recommended by guidelines as an effective strategy to obtain rapid and optimal BP control in hypertensive patients. However, the prescription of multiple BP-lowering medications increases the pill burden, potentially reducing medication adherence. Guidelines also recommend using single pill combinations(SPCs) containing ≥2 anti-hypertensive medications as a practical approach to simplify treatment schedules and possibly improve adherence. Yet, real-world evidence on the association between SPC or free combination of BP-lowering medications and hyperthensive patient outcome remains limited. Purpose We compared the association of SPC versus free-pill combination(free) on cardiovascular outcomes and all-cause mortality in hypertensive patients treated with perindopril(PER)-based therapies in real clinical practice in Italy. Methods A retrospective analysis was conducted using administrative databases covering 6.7 million health-assisted Italian residents. Among adults with hospitalization discharge diagnosis or exemption code for hypertension between 2010 and 2021, the study included patients prescribed with a combination of PER with amlodipine(AML) and/or indapamide(IND), either as SPC or free or mixed (SPC plus separate pill) combinations. Results The analysis included 24,476 hypertensive subjects receiving a PER-based therapy, 22,663 (93%) of them using SPC, 1458 (6%) free and 355 (1.4%) mixed. The last cohort was not included in the analysis due to the small sample size (N=355). The patients in the free cohort were significantly older than those in the SPC cohort (69.5±12.3 vs. 64.3±12.2 years, p&amp;lt;0.001), showed a higher number of pre-existing comorbidities (0.5±0.8 vs. 0.4±0.7, p&amp;lt;0.001), and received a larger number of different medications (pill burden: 1.2±1.7 vs. 0.7±1.3, p&amp;lt;0.001). To minimize selection bias, the groups were balanced with propensity score and inverse probability weighting (IPW), adjusting for baseline covariates, including comorbidity profile and pill burden. The IPW-adjusted Kaplan-Meier plots and Cox’s proportional hazard model (Table 1) revealed that, compared with SPC users, patients on free regimens had a significantly increased risk of all-cause mortality (36%, p&amp;lt;0.001), all cardiovascular events (45%, p&amp;lt;0.001), ischemic heart disease (29%, p&amp;lt;0.05), cerebrovascular events (84%, p&amp;lt;0.001), and occurrence of the composite outcome cardiovascular events/all-cause mortality (40%, p&amp;lt;0.001). Conclusions This real-world data from a large Italian administrative dataset suggested that PER-based anti-hypertensive therapy with SPC results in significant clinical benefits in terms of lowered risk of cardiovascular/cerebrovascular events and all-cause mortality. Reducing pill burden and simplifying therapeutic schedules is of crucial importance to maximize the potential benefits derived from the prescription of anti-hypertensive treatment.

Adherence to treatment in patients with arterial hypertension at the wartime conditions in Ukrainian population

Abstract Background Adherence to therapy significantly affects the course and prognosis of the disease. However, the impact of military operations and related factors on adherence to therapy has not been studied. Purpose The aim of the study was to evaluate additional factors influencing adherence to antihypertensive treatment in wartime. Materials and Methods A total of 1299 patients with arterial hypertension from different regions of Ukraine included into the study. All regions were divided into 3 zones: active hostilities; regions with moderate intensity; relatively calm regions. Besides traditional factors (age, education, concomitant pathology, type of therapy), the individual patients’ status was included to analysis as being a resident of a given region, an immigrant from an occupied territory or from a region of hostilities, or a person temporarily displaced. Analysis was performed in 4 treatment groups: 1 – fixed three-component combination olmesartan medoxomil/ amlodipine/ hydrochlorothiazide, 2 – fixed two-component combination olmesartan/ hydrochlorothiazide, 3 – fixed two-component therapy with olmesartan/ amlodipine, 4 - other antihypertensive therapy. Adherence was assessed at 1, 2 and 3 treatment months. Uni- and multivariate statistical analyses was performed to identify factors independently associated with treatment adherence. Results In total, 50 patients stopped the drug during the first month (3.8%), 9.8% stopped medication after 2 months, and 19.1% after 3 months. When analyzing patients' adherence depending on whether or not the doctor arrived from another region, we found that the percentage of patients who stopped treatment was almost twice higher if the doctor was displaced (32%), compared to doctors who remained in the places (18%). Based on results of comparative analysis, adherence to therapy was influenced by several factors: age, presence of concomitant coronary artery disease, staying in a high-risk region, number of pills, and prescribed drug. After 3 months adherence was 89% in patients who received 1 tablet per day, 84% - 2 tablets, 82% - 3-5 tablets, and 52% - more than 5 pills. The highest adherence was observed with the three-component pill and with combination of olmesartan and amlodipine. These combinations showed higher adherence compared to other types of therapy. Patient's level of education had no effect on adherence to therapy. Multivariate regression analysis showed, that age over 55 years (p=0.01) and patient’s being in dangerous area (p&amp;lt;0.0001) had significant independent negative influence on adherence. The use of two-component combination olmesartan/amlodipine or three-component therapy significantly increased adherence (p&amp;lt;0.0001). Conclusion In the wartime adherence to antihypertensive treatment depends both on previously known and specific factors - activity of hostilities in the region, as well as relocation of both patients and prescribing physicians to another region.