bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECT OF NEBIVOLOL MONOTHERAPY OR COMBINATION THERAPY ON BLOOD PRESSURE LEVELS IN PATIENTS WITH HYPERTENSION: META-ANALYSIS OF 91 RANDOMIZED CONTROLLED TRIALS
Authors: Manolis Athanasios , Karakasis Paschalis , Patoulias Dimitrios , Kallistratos Manolis , Koutsaki Maria , Pittaras Antreas , Doumas Michalis 
Published: May 2024

Objective:
The present study aimed to systematically appraise and quantitatively summarize the available evidence from published randomized controlled trials (RCTs) considering the effect of nebivolol on blood pressure (BP) levels in patients with hypertension.

Design and method:
The literature search was performed through Medline (via PubMed), Cochrane Library and Scopus until December 15, 2023. Double-independent study selection, data extraction and quality assessment were performed. Evidence was pooled with three-level mixed-effects meta-analysis.

Results:
In total, 7,737 participants with hypertension, who were treated with nebivolol, were analyzed across 91 RCTs. Most trials had a high risk of bias according to the Cochrane
Collaboration tool (RoB2). Nebivolol was associated with significantly greater reduction in office systolic and diastolic BP compared to placebo (MD = -6.01 mmHg; 95% CI= [-7.46, -
4.55] and MD = -5.01 mmHg; 95% CI= [-5.91, -4.11], respectively). Moreover, nebivolol resulted in a similar reduction in systolic BP (MD = -0.22 mmHg; 95% CI= [-0.91, 0.46]) and a significantly greater reduction in diastolic BP compared to active comparator (MD = -0.71 mmHg; 95% CI= [-1.27, -0.16]). When considering the effect of nebivolol on 24-hour ambulatory BP, notable reductions were observed compared to placebo. In contrast, compared to the active comparator, there was no significant difference in ambulatory systolic BP reduction, but a significant reduction in ambulatory diastolic BP favoring nebivolol was noted. Based on moderator analyses, the impact of nebivolol on the pooled estimates remained independent of the duration of RCTs, gender, age, body mass index, history of diabetes or heart failure.

Conclusions:
Our findings suggest that nebivolol resulted in a significant reduction in BP compared to placebo and seemed to be non-inferior to active comparator in terms of BP reduction. When considering the effect of nebivolol on 24-hour ambulatory BP, nebivolol was superior to placebo, while compared to the active comparator, there was no significant difference in ambulatory systolic BP reduction, but a significant reduction in ambulatory diastolic BP. Future, large-scale, and meticulously designed trials are necessary to further establish the place of nebivolol in the treatment algorithm of hypertension.
A PRESCRIPTION TREND ANALYSIS OF ANTIHYPERTENSIVE PHARMACOTHERAPY ACROSS DIFFERENT SPECIALTIES IN INDIA
Authors: Vishavadia Krunal , Solanki Sandip , Kulkarni Girish , Prajapati Hiren 
Published: May 2024

Objective:
To evaluate the temporal trends in the prescription patterns of antihypertensive medications among healthcare practitioners in India.

Design and method:
The IQVIA (formerly Quintiles and IMS Health) prescription audit data came from prescriptions of a panel of 6000 private sector primary care clinicians for the different classes of antihypertensive drugs; beta-blockers (BB), calcium channel blockers (CCB), angiotensin receptor blockers (ARB), angiotensin-converting enzyme (ACE) inhibitors, and diuretics were examined. The analysis encompassed the period from 2014 to 2022. Additionally, combinations of these drug classes involving two or three medications were also subject to analysis.

Results:
Cardiologists’ prescription rates for antihypertensive medications stood at 21% in 2017 and decreased to 19% by 2023. In 2023, the highest rate of prescribing antihypertensive drugs was observed among consultant physicians, with a rate of 30%, followed by general practitioners at 27%. In addition, during COVID-19, the prescription share of general practitioners was highest (31%). Among anti-hypertensive medications, the prescription rates for BBs were highest (32%), followed by ARBs & CCBs (25% & 24% respectively). Single-drug formulation of antihypertensive medications was the most preferred (60%) among Indian clinicians. Prescription shares of fixed-dose combinations (FDC) of two antihypertensive drugs showed a slight decline (36% in 2017 to 34% in 2023) & FDCs of triple-drug exhibited an upward trend (3% in 2017 to 5% in 2023). Among the two drug FDCs, ARB & diuretics were most preferred (25% prescription share) & triple drug FDCs, CCB, ARB & diuretics were most preferred.

Conclusions:
Cardiovascular medications hold a prominent position in the Indian pharmaceutical market, with antihypertensives standing out as one of the most frequently prescribed treatments. Consultant physicians and general practitioners manage the majority of hypertension cases. Notably, there has been an observed rise in the preference for triple-drug combinations of antihypertensive medications, indicating a trend toward a more aggressive approach to hypertension management among Indian clinicians. The insights gleaned from this investigation can further assist healthcare professionals in crafting tailored treatment strategies for individuals grappling with hypertension. Such personalized approaches hold promise in enhancing treatment adherence and ultimately improving the QoL.
POOR ADHERENCE IS A CRUCIAL POOR PROGNOSIS FACTOR IN RESISTANT HYPERTENSION: RESULTS FROM A NATIONWIDE COHORT STUDY
Authors: Lee Chan Joo , Lee Ho Kyu , Seo Jiwon , Kang Dayoung , Hwang Jinseub , Park Sungha , Pyun Wook Bum 
Published: May 2024

Objective:
Poor adherence is one of the most common causes of hypertension treatment failure. However, the prognostic significance of medication adherence in resistant hypertension is unknown.

Design and method:
We sampled 25% of hypertensive patients from the Korean National Health Insurance Service Database from 2013 to 2018 and selected patients without a history of cardiovascular disease who met the definition of resistant hypertension with a target blood pressure of 140/90 mm Hg. Adherence was calculated as the proportion of days covered (PDC) for one year after the index date and divided into the poor (PDC <0.6), suboptimal (0.6<= PDC <0.8), and optimal (PDC >=0.8) groups. The primary outcome was a composite of all-cause of death, myocardial infarction (MI), stroke, and heart failure during follow-up. Secondary outcomes were individual events of the primary outcome, end-stage renal disease (ESRD), and atrial fibrillation.

Results:
The poor group, suboptimal group, and optimal group were 3,852 (5.7%), 11,667 (17.3%), and 51,879 (77%), respectively. Compared to other groups, the poor group was younger, had a higher proportion of smokers and alcohol drinkers, exercised less, and had a lower prevalence of comorbidities. During 5.6 years of median follow-up, the incidence of the primary outcome in the poor group, suboptimal group, and optimal group were 30.7, 26.6, and 28.9/1,000 person-years, respectively. In a multivariable Cox proportional hazard model, the risk of the primary outcome was 1.47 times higher in the poor group and 1.31 times higher in the suboptimal group compared to the optimal group (all P values <0.001). In the poor group, the risk was 1.37 to 1.52 times higher for all-cause death, MI, and stroke and 1.9 times higher for hemorrhagic stroke. The suboptimal group showed similar results but with a lower increased risk than the poor group.

Conclusions:
Even in resistant hypertension, poor adherence is strongly associated with an increased risk of clinical events. Based on this study, prospective studies are warranted to see if improving medication adherence can lower the risk of clinical events in patients with resistant hypertension.
COGNITIVE FUNCTION, CAROTID STRUCTURAL CHANGES AND KIDNEY FUNCTION: ARE THERE RELATIONSHIP IN PATIENTS WITH RESISTANCE HYPERTENSION?
Authors: Gulkevych Oksana , Bezrodna Larisa , Logvinenko Alla , Bezrodnyj Volodymyr , Bozhenko Galyna 
Published: May 2024

Objective:
To evaluate the relationship between cognitive function, carotid structural changes and kidney function in patients with resistance hypertension (RH).

Design and method:
In 98 pts with RH (average age 54,3±2,5; 55 males) we measure ultrasonographically carotid diameter (CD) and intima-media thickness (IMT). Cognitive function was assessed in all pts by Montreal cognitive assessment (MoCA) test. All patients underwent full clinical and laboratory screening evaluation. Kidney function was estimated by glomerular filtration rate (GFR) using the CKD-EPI creatinine equation. All pts were divided into 2 groups depending on the value of GFR: group I (n=59) - GFR > 60 (ml/min/1,73m2) and group II (n=39) – GFR < 60 (ml/min/1,73m2).

Results:
Patients with GFR < 60 (ml/min/1,73m2) had significantly greater carotid structural changes: pts of gr.I had CD 7,79±0,07 mm and IMT 1,22±0,02 mm vs pts of gr.II 8,92±0,08 mm (p<0,05) and 1,77±0,03 mm (p<0,05) accordingly. Cognitive function was more impaired in pts gr II: MoCA score of gr I pts was 25,3±1,8 and gr II pts – 22,1±1,4. GFR was significantly correlated with MoCA score and carotid structure (MoCA score: r=0,61, p<0,05, CD: r=0,55, p<0,05, IMT: r=0,68, p<0,05). Adjustment for age, blood pressure, BMI and gender did not abolish association between GFR and MoCA score, parameters of carotid structure.

Conclusions:
There is relationship between kidney function, carotid structure and cognitive function in pts with resistance hypertension. GFR may have prognostic value for cognitive function damage in patients with resistance hypertension.
BLOOD PRESSURE RESPONDERS TO RENAL DENERVATION BASED ON A NEW DEFINITION
Authors: Bytyqi Venera , Kannenkeril Dennis , Striepe Kristina , Bosch Agnes , Schiffer Mario , Schmid Axel , Uder Michael , Schmieder Roland E. 
Published: May 2024

Objective:
Identifying predictors of blood pressure (BP) response to renal denervation (RDN) is an unmet need for patient selection. Any antihypertensive intervention follows the law of the inital value, which means that the baseline BP predicts the BP change, a phenomenon known as Wilder‘s Principle (European Heart Journal, 2015, 36, 576-579). Thus, any observed change in BP after renal denervation is the sum of the change in BP depending on the baseline BP and the specific BP reduction related to RDN. Based on this concept, we propose a new definition of BP responders.

Design and method:
In our center, a total of 127 patients with uncontrolled hypertension underwent RDN and 24h ambulatory BP was measured at baseline, 6- and 12 months after the procedure. According to the Wilder's principle, the decrease in the 24h ambulatory systolic BP (SBP) was related to the baseline 24h SBP (p=<0.001, r=-0.466, y=69.28–0.52∗x). Subsequently, we calculated the predicated decrease in 24h SBP and subtracted this from the the observed decrease in 24h SBP, thereby getting the specific or residual effect of SBP decrease. According to this RDN specific change of 24h SBP, the study cohort was divided into tertials: RDN responders, neutral responders and non-responders.

Results:
Our study population with mean of age of 59 years consisted of 74% males and 55% with type 2 Diabetes (T2D). The RDN specific (residual) 24-hour ambulatory blood pressure decreased by -14.4/-8.8mHg (responder group), 1.4/0.4mmHg (neutral group) und 15.7/8.5 mmHg (non-responder group) twelve months after RDN (see table). According to our new definition of BP-responders to RDN, the RDN responder group was characterized only by lower number of antihypertensive medication (p=0.002), low BMI (p<0.001), and the absence of T2D (p=0.013).

Conclusions:
We propose a new definition of responders to RDN, separating the BP- changes related to the baseline BP from those related to the reduction of the sympathetic nerve activity after RDN. Following this approach, we identified low BMI, less antihypertensive medication and absence of T2D as positive predictors for BP response to renal denervation.
ASSOCIATION OF INFLAMMATION AND ATHEROGENIC DYSLIPIDEMIA WITH INCIDENT CARDIOMETABOLIC DIASEASE: A LONGITUDINAL COHORT STUDY
Authors: Wang Chi , Zheng Mengyi , Chen Shuohua , Wu Shouling , Xue Hao 
Published: May 2024

Objective:
Inflammation and atherogenic dyslipidemia promote each other establishing a vicious circle. This study aimed to examine their joint association with cardiometabolic disease (CMD) and whether the temporal relationship between them is associated with risk of CMD.

Design and method:
This study included 78,211 participants without history of cardiovascular disease and diabetes mellitus at baseline in 2006. We categorized the participants into six groups according to their C-reactive protein (CRP, <1,1–3, or >=3 mg/L) level and atherogenic index of plasma (AIP, <-0.08 or >=-0.08). Incident CMD was defined as the first occurrence of a CMD event during follow-up, including cardiovascular disease (including myocardial infarction, coronary revascularization, heart failure, ischemic stroke, and hemorrhagic stroke) and type 2 diabetes mellitus (T2DM). Cox regression models were used to estimate the risk of CMD across CRP-AIP groups. The temporal relationship between CRP and AIP was assessed by cross-lagged analysis in the 53,715 participants who attended the resurvey in 2010. The association of this temporal relationship with subsequent CMD risk was examined by mediation analysis.

Results:
After adjusting for potential confounders, increased CRP and elevated AIP were cumulatively associated with a higher risk of CMD, where participants with a CRP of >=3 mg/L and an AIP of >=-0.08 had a hazard ratio of 1.63 (95% confidence interval [CI], 1.55–1.71) for CMD, 1.43 (95% CI, 1.33-1.55) for cardiovascular disease, and 1.71 (95% CI, 1.60-1.82) for T2DM, compared with those with low CRP and AIP values. (Table 1). In cross-lagged analysis, the standard regression coefficient from baseline CRP to follow-up AIP was greater than that from baseline AIP to follow-up CRP (0.069 [95% CI, 0.061–0.077] versus 0.014 [95% CI, 0.005–0.023], P difference <0.001) (Table 2). Furthermore, AIP partially mediated the effect of CRP on incident CMD. The mediation effect was 15.56% (95% CI, 12.87–18.25) for CMD, 10.03% (95% CI, 6.19–13.88) for cardiovascular disease, and 18.82% (95% CI, 15.36–22.28) for T2DM (Figure 1).

Conclusions:
CRP and AIP were additively associated with risk of CMD. Increased CRP might precede elevated AIP, and AIP partially mediated the association between CRP and incident CMD.
TEN-YEAR FOLLOW-UP STUDY REGARDING TREATMENT COMPLIANCE AND CARDIOVASCULAR EVENTS IN YOUNG FIRST-DIAGNOSED AND NEVER-TREATED HYPERTENSIVES OF A HYPERTENSION-EXCELLENCE-CENTER
Authors: Triantafyllidi Helen , Benas Dimitrios , Sioula Konstantina , Fampri Anastasia , Birmpa Dionysia , Oikonomidis Ignatios 
Published: May 2024

Objective:
Early-onset arterial hypertension (AH) is associated with increased risk for cardiovascular (CV) disease if left untreated. Treatment is based on CV risk estimation in each hypertensive. Compliance of each individual in proposed lifestyle changes and medical treatment is paramount. We aimed to investigate compliance in medical treatment and set as primary endpoint of the study the incidence of any CV events[CV death, acute myocardial infarction (AMI), stroke] and all-cause death of a cohort of young first-diagnosed and never-treated hypertensives of a European Society of Hypertension (ESH) Excellence Center.

Design and method:
We studied 220 young, non-diabetic (<=50 years) first-diagnosed and never-treated hypertensive patients[42±7years,70% males,41% smokers,BMI=29±5,24-h ambulatory blood pressure monitoring (ABPM)=142±10/91±9mmHg,low-density-lipoprotein cholesterol (LDL-C)=133±36mg/dl,49% had >=1 hypertension-mediated-organ-damage (HMOD)] visiting our ESH Excellence Center(2004-2021). All patients were apparently healthy with no co-morbidities. In each patient, the presence of HMOD was evaluated at baseline(aortic stiffness,left ventricular hypertrophy,coronary flow reserve,diastolic dysfunction). The cohort was re-evaluated at 10±4years post-medical treatment initiation regarding compliance as well as study primary endpoint.

Results:
191/220 (87%) young hypertensives[at baseline,42±7years,70% males,40% smokers,body mass index (BMI)=29.5,24-h ABPM=142±10/91±9 mmHg,LDL-C=133±36mg/dl,49% had>1 HMOD) participated in the follow-up study while 29 (13%) patients were lost. We found that 17/191 (9%) quit medical treatment. Home or office blood pressure (BP) was confirmed as controlled(<140/90mmHg) in 151/191 (79%) patients. Regarding CV events, 7/191 (4%) hypertensive patients (at baseline,44±4 years,6/7 males,71% smokers,BMI=30±4,24-h ABPM=142±13/89±11mmHg,LDL-C=175±33mg/dl,87% had>1 HMOD) had an AMI at 6±4 years post-treatment initiation while 1/191 (0.5%) patient died due to lung cancer. Hypertensives with CV events differed regarding increased LDL-C at baseline(175±33vs.131±36, p=0.007),more smokers (p=0.04) and HMOD>1 (p=0.02) compared to the rest of the young hypertensives.

Conclusions:
Compliance regarding medical treatment was sustained in 9/10 young hypertensives during the 10-year follow-up. Just 4% of the population, smokers with increased LDL-C and HMOD>1, suffered an AMI despite compliance in medical antihypertensive treatment. Subsequently, treating AH in young people needs both lifestyle changes (quit smoking) and medical treatment (hypertension plus hyperlipidemia) in order to prevent future CV events.
SERUM CALCIUM IS ASSOCIATED WITH PERIPHERAL AND CENTRAL BLOOD PRESSURE IN DIFFERENT SAMPLES
Authors: Sartorio Andrea , Giontella Alice , Dal Pont Chiara , Minuz Pietro , Melander Olle , Fava Cristiano 
Published: May 2024

Objective:
Calcium homeostasis plays a crucial role in both contractility and relaxation mechanisms, determining the vasoconstriction and vasodilation of blood vessels. Some studies have reported a positive correlation between serum calcium and blood pressure (BP) levels, hypertension, metabolic syndrome, and type 2 diabetes, while others have not. Given these conflicting findings, we investigated the relationship between serum calcium and BP in three distinct samples. Our objective was to confirm the existence of a positive correlation between calcium levels and BP and to assess whether this relationship extends to central BP.

Design and method:
Serum calcium levels were measured in a restricted sample of patients referred to our ESH Excellence Center in Verona (n=56) with a suspicion of secondary hypertension, as well as in two large population-based studies from Sweden, the Malmö Preventive Project (MPP, n= 17,843) and from United Kingdom, the UK Biobank (UKB, n= 330,000). Central BP was estimated by tonometry performed with SphygmoCor Xcel.

Results:
In the Verona sample, the patients, predominantly receiving antihypertensive therapy based on calcium antagonists, serum calcium correlated with central systolic BP (r=0.37; p<0.01), and this association persisted even after adjusting for age, sex, and BMI. In the MPP, baseline serum calcium was associated with both systolic (beta 0.60, 95% CI 0.30-0.89; p<0.001) and diastolic BP (beta 0.44, 95% CI 0.26-0.62; p<0.001) after adjustment for age, sex, BMI, and antihypertensive therapy. Similarly, in the UKB, the association between both systolic (beta 1.79, 95% CI 1.74-1.85; p<10^15) and diastolic BP (beta 0.98, 95% CI 0.95-1.02; p<10 ^15) and serum calcium was confirmed after the same adjustments.

Conclusions:
In different samples, serum calcium consistently associates with increased BP. Further studies are warranted to elucidate whether this association is influenced by hormones regulating this electrolyte and/or by dietary calcium intake.
LP(A) IN HYPERTENSIVE PATIENTS AS A PREDICTOR OF CARDIOVASCULAR EVENTS
Authors: Renna Nicolás Federico , Ramirez Eliel Ivan , Tenuta Maria De Los Ang , Corral Pablo , Cobo Augusto Lavalle , Gimenez Sergio , Arrupe Matias , Diez Emiliano , Ramirez Jesica Magali 
Published: May 2024

Objective:
This study aims to analyze the relationship between Lp(a) levels and HT, determining whether this association implies an increased risk. In this way, the goal is to assess the utility of this relationship as an effective tool for cardiovascular risk stratification.

Design and method:
A retrospective study with a history of recent coronary events was conducted from June 2020 to September 2023. Data were obtained from the computerized medical records. Demographic data, history of HT diagnosis, BMI, current tobacco use, family history, sedentary behavior, pharmacological treatment with statins and antihypertensives were collected. Additionally, serum levels of total cholesterol (Col-T), LDL-chol, HDL-chol and Lp(a) were documented. The nature of the event (first occurrence or readmission) was also recorded. Statistics analysis of regression and variance (ANOVA) was performed.

Results:
A total of 105 patients were included. Age average was 59.7±13, 60% were obese, 39% were current smokers, 31% were diabetic and 66% had sedentary habits (mean ± SD). Chol-LDL values was 136.4±44 and Lp(a) 89±113 (mg/dL mean ± SD). Lp(a) showed a significant correlation with readmissions due to ischemic heart disease, sedentary behavior, and LDL-C levels. Additionally, its value is independent of the other variables. When the regression analysis of Lp(a) (Lowess) was performed, adjusting for age, it became evident that patients with arterial hypertension and cardiovascular events have much higher levels of Lp(a) compared to those without events. Figure 1

Conclusions:
According to available studies, the guideline recommends a universal cutoff point of 100 nmol/L (approximately 50 mg/dL), which approximates the 80th percentile in Caucasian populations in the United States. However, the use of this cutoff point remains a topic of debate among many experts in the lipid community,. This study highlights that in a population of hypertensive patients with elevated Lp(a), early cardiovascular events are observed. The incorporation of this variable into the patients’ risk score could be a strategy for reducing cardiovascular events.