24-h Systolic Blood Pressure Research Articles

The effects of extra virgin olive oil or butter on cardiovascular biomarkers in European and Chinese males in the UK: A pilot randomised crossover trial.

Purpose: No dietary interventional studies have reported the impact of olive oil on cardiovascular risk markers in groups of different ethnic origins. We report a pilot randomised controlled trial of an intervention supplementing extra virgin olive oil (EVOO) on markers of cardiovascular risk among East Asian Chinese, and European Caucasian individuals. Methods: A cross-over, randomised controlled dietary intervention for 2 weeks was undertaken. Thirty-two adults, healthy, individuals of Chinese and European origin took part in this study. 24-h ambulatory systolic and diastolic blood pressure (SBP, DBP), and blood lipids, were assessed. Results: Positive benefits of EVOO consumption were observed in all participants. Lower 24-h ambulatory SBP (-4.3 mmHg; p = 0.020), and day-time SBP (5.528 mmHg; p = 0.008), night-time DBP (-3.784 mmHg; p = 0.008) and night-time MAP (-3.747 mmHg; p = 0.007) were seen in all participants independently of covariates. In addition, total cholesterol (7.9 mg/dL; p = 0.017) and LDL-cholesterol (6.5 mg/dL; p = 0.028) were increased with butter but not with olive oil. No significant difference in other cardiovascular risk factors were observed. However, differences were observed between Caucasians and East Asian individuals in the absence of significant differences in lifestyle. Conclusion: This pilot study suggests that consumption of EVOO should be advocated as a healthier dietary fat and recommended to replace butter as a dietary strategy to improve cardiovascular health in both Caucasians and East Asian individuals.

The Association between Diverticular Rebleeding and Early-Morning Blood Pressure and Surge: A Prospective Observational Trial

Introduction: Colonic diverticular bleeding is the major cause of lower gastrointestinal bleeding. Hypertension is a major risk factor for diverticular rebleeding. Direct evidence of an association between actual 24-h blood pressure (BP) and rebleeding is lacking. Therefore, we analyzed the association between 24-h BP and diverticular rebleeding. Methods: We performed a prospective observational cohort trial involving hospitalized patients with colonic diverticular bleeding. We performed 24-h BP measurements (ambulatory BP monitoring [ABPM]) in the patients. The primary outcome was diverticular rebleeding. We evaluated the 24-h BP difference and the morning and pre-awaking BP surge between rebleeding and non-rebleeding patients. Morning BP surge was defined as early-morning systolic BP minus the lowest night systolic BP >45 mm Hg (highest quartile of morning BP surge). The pre-awaking BP surge was defined as the difference between morning BP and pre-awaking BP. Results: Of 47 patients, 17 were excluded, leaving 30 who underwent ABPM. Of the 30 patients, 4 (13.33%) had rebleeding. The mean 24-h systolic and diastolic BP were 125.05 and 76.19 mm Hg in rebleeding patients and 129.98 and 81.77 mm Hg in non-rebleeding patients, respectively. Systolic BP at 5:00 (difference −23.53 mm Hg, p = 0.031) and 11:30 (difference −31.48 mm Hg, p = 0.006) was significantly lower in rebleeding patients than in non-rebleeding patients. Diastolic BP at 2:30 (difference −17.75 mm Hg, p = 0.023) and 5:00 (difference −16.12 mm Hg, p = 0.043) was significantly lower in rebleeding patients than in non-rebleeding patients. A morning surge was observed in one rebleeding patient and no non-rebleeding patients. The pre-awaking surge was significantly higher in rebleeding patients (28.44 mm Hg) than in non-rebleeding patients (9.30 mm Hg) (p = 0.015). Conclusion: Lower BP in the early-morning and a higher pre-awaking surge were risk factors for diverticular rebleeding. A 24-h ABPM can identify these BP findings and reduce the risk of rebleeding by enabling interventions in patients with diverticular bleeding.

Blood pressure, arterial stiffness, and cardiovascular risk profiles in 8-12-year-old children following preeclampsia (FINNCARE-study).

The aim was to study if children following preeclampsia (PE) develop alterations in blood pressure (BP) and arterial stiffness already early in life, and how this is associated with gestational, perinatal and child cardiovascular risk profiles. One hundred eighty-two PE (46 early-onset with diagnosis before 34 gestational weeks, and 136 late-onset) and 85 non-PE children were assessed 8-12 years from delivery. Office and 24-h ambulatory BP, body composition, anthropometrics, lipids, glucose, inflammatory markers, and tonometry-derived pulse wave velocity (PWV) and central BPs were assessed. Office BP, central BPs, 24-h systolic BP (SBP) and pulse pressure (PP) were higher in PE compared with non-PE. Early-onset PE children had the highest SBP, SBP-loads, and PP. SBP nondipping during night-time was common among PE. The higher child 24-h mean SBP among PE was explained by maternal SBP at first antenatal visit and prematurity (birth weight or gestational weeks), but child 24-h mean PP remained related with PE and child adiposity after adjustments. Central and peripheral PWVs were elevated in late-onset PE subgroup only and attributed to child age and anthropometrics, child and maternal office SBP at follow-up, but relations with maternal antenatal SBPs and prematurity were not found. There were no differences in body anthropometrics, composition, or blood parameters. PE children develop an adverse BP profile and arterial stiffness early in life. PE-related BP is related with maternal gestational BP and prematurity, whereas arterial stiffness is determined by child characteristics at follow-up. The alterations in BP are pronounced in early-onset PE.Clinical Trial Registration information: https://clinicaltrials.gov/ct2/show/NCT04676295ClinicalTrials.gov Identifier: NCT04676295.

PHARMACOLOGICAL AND INTERVENTIONAL TREATMENT OF RESISTANT HYPERTENSION. A NETWORK META-ANALYSIS

Objective: Resistant hypertension is associated with a high risk of cardiovascular disease, chronic kidney disease and mortality. Yet, its management is still challenging. This study aims to establish the comparative effectiveness of pharmacologic and interventional treatments by conducting a network meta-analysis. Design and method: We systematically searched MEDLINE, Cochrane Register of Controlled Trials (CENTRAL) and Web of Science Core Collection in March 2022. Randomized controlled trials comparing treatment options as add-on therapy for management of resistant hypertension were included. Outcomes were blood pressure changes, measured in the office and in 24h ABPM. We applied a frequentist random effects model to perform a network meta-analysis combining placebo medication and sham procedure as the reference comparator. Results: From 4771 records, 24 studies met our inclusion criteria with 3458 included patients in total. 12 active treatment alternatives were analyzed. Among all comparators, spironolactone had the highest-ranking probability and was considered as the most effective treatment to reduce office systolic blood pressure (-13.30 mmHg [-17.89; -8.72]; P < 0.0001) and 24h systolic blood pressure (-8.46 mmHg [-12.54; -4.38]; P < 0.0001) in patients with resistant hypertension. Conclusions: Among all pharmacologic and interventional treatments, spironolactone has been found to be most effective in reducing office and 24h systolic blood pressure as an add-on therapy for resistant hypertension. Our study provides an evidence-based and valid reference in clinical decision-making.

DIETARY SODIUM RESTRICTION REDUCES NOCTURNAL BLOOD PRESSURE IN PATIENTS WITH TREATMENT RESISTANT HYPERTENSION

Objective: Patients with treatment resistant hypertension (TRH) are characterised by lack of blood pressure (BP) control despite antihypertensive treatment. They are at particular risk of cardiovascular disease and more likely to experience BP increase as a response to sodium loading than other individuals. In this study, we aimed to analyse if self-performed dietary sodium restriction could be implemented in patients with TRH. Moreover, we aimed to analyse the effect of this on nocturnal and 24h BP, and how BP changes were correlated to changes in plasma levels of BNP, nitric oxide and body water content. Design and method: The study was conducted as an interventional cross-over study including patients with TRH from 20-70 years. Patients were screened with 24h ambulatory BP monitoring initiated after observed intake of usual antihypertensive medication. They were included if 24h systolic BP>130/80 mmHg. Study participation included two periods of 14 days; a standard period with usual diet and an interventional period with instructed dietary sodium restriction and handed-out sodium-free bread. At the end of each period, patients were examined with 24h BP monitoring, 24h urine collection (sodium excretion), blood samples (nitric oxide, BNP), and bioimpedance measurement (body water content). Results: Participation was completed by 15 patients with mean age 59 years and mean 24h BP 144/82 mmHg. Mean baseline urinary sodium excretion was 192(86) mmol/24h (11.2 grams of salt). As seen in Table 1, sodium excretion was reduced to 91 mmol/24h equalling 5.3 grams of salt. BP levels were reduced significantly. Plasma levels of nitric oxide increased significantly, and this was correlated to the change in 24h BP. Total body water content and plasma levels of BNP was reduced significantly. The changes in BP were not correlated to changes in sodium excretion, body water or BNP. Conclusions: Self-performed dietary sodium restriction could be implemented resulting in a significant reduction in BP levels. BP change was not related to changes in body water or sodium excretion. Increased levels of nitric oxide may be evidence of improved endothelial function and may be one of the involved mechanisms in BP decrease following sodium restriction

A Prospective, Randomized Open-Label Study for Assessment of Antihypertensive Effect of Telmisartan Versus Cilnidipine Using Ambulatory Blood Pressure Monitoring (START ABPM Study).

The antihypertensive agent telmisartan is an angiotensin II receptor blocker with a terminal elimination half-life of 24 h and has a high lipophilicity, thereby enhancing its bioavailability. Another antihypertensive agent, cilnidipine is a calcium antagonist and has dual mode of action on the calcium channels. This study aimed at determining effect of these drugs on ambulatory blood pressure (BP) levels. A randomized, open-label, single-center study was conducted during 2021 - 2022 on newly diagnosed adult patients with stage-I hypertension, in a mega city of India. Forty eligible patients were randomized to telmisartan (40 mg) and cilnidipine (10 mg) groups, with once daily dose administered for 56 consecutive days. Ambulatory blood pressure monitoring (ABPM) (24 h) was performed pre- and post-treatment, and the ABPM-derived parameters were compared statistically. Statistically significant mean reductions were observed in all BP endpoints in telmisartan group but only in 24-h systolic blood pressure (SBP), daytime and nighttime SBP, and manual SBP and diastolic blood pressure (DBP) in cilnidipine group. The mean change from baseline to day 56 between two treatment groups showed statistical significance in last 6-h SBP (P = 0.01) and DBP (P = 0.014), and morning SBP (P = 0.019) and DBP (P = 0.028). The percent nocturnal drop within and between groups was statistically nonsignificant. Also, the between group mean SBP and DBP smoothness index differed nonsignificantly. Telmisartan and cilnidipine once daily were effective and well tolerated in the treatment of newly diagnosed stage-I hypertension. Telmisartan provided sustained 24-h BP control and may offer advantages over cilnidipine in terms of BP reductions, particularly over the 18- to 24-h post-dose period or critical early morning hours.

24HOUR, HOME AND CLINIC BLOOD PRESSURE FOR THE PREDICTION OF LEFT VENTRICULAR HYPERTROPHY IN UNTREATED HYPERTENSIVE POPULATION

Objective: The aim of this study was to investigate which way of measuring blood pressure (BP), clinic, home or 24h-ABPM, can predict better left ventricular hypertrophy in the untreated hypertensive population. Design and method: 175 consecutive subjects (42% male) aged 57.9±14.9 years were included in the study. Subjects were never treated before for hypertension. All subjects underwent 24h-ABPM on a usual working day. Home BP monitor was provided to all patients for 7 days, while office BP was measured in the clinic using a mercury sphygmomanometer. Left ventricular hypertrophy was evaluated by a cardiologist with the use of a 3D echocardiography. Results: In the univariate analysis, only home systolic and diastolic BP were independently associated with left ventricular hypertrophy, while both clinic and 24hour systolic and diastolic BP found not to be. From ROC curves for left ventricular hypertrophy, AUC of home systolic BP monitor (0.758, p<0.05) was larger than that of 24h (0.538, p>0.05) and clinic BP (0.497, p<0.05). As regards DBP, the ROC curves suggest no discrimination for the different ways of BP measurement. Conclusions: Home systolic BP can be a better predictor of left ventricular hypertrophy in untreated population, when compared to 24h and office systolic BP. This result shows the importance of home monitoring for the prediction of left ventricular hypertrophy, even in the untreated population.

BLOOD PRESSURE REDUCTION AFTER RENAL DENERVATION IN PATIENTS WITH OR WITHOUT CHRONIC KIDNEY DISEASE: THE ERLANGER EXPERIENCE

Objective: Renal denervation (RDN) has emerged as an adjacent option for the treatment of hypertension. This analysis of the ERLANGER registry aimed of comparing the blood pressure (BP) lowering effects and safety of RDN in patients with and without CKD. Design and method: Radiofrequency, ultrasound or alcohol-infusion device based RDN was performed in 47 patients with and 127 without CKD. Office and 24-h ambulatory BP were measured at baseline, after 6 and 12 months. We splitted the study cohort based on the median systolic 24h ABP reduction after 6 months into responders and non-responders and compared baseline characteristics between these groups. CKD was defined by clinical diagnosis, estimated glomerular filtration rate (eGFR: 15-59 ml/min/1.73m2) or A2 albuminuria (> = 30 mg/g creatinine ). Results: 174 patients with a mean age of 59.0±10 were followed up for at least 12 months. At baseline mean eGFR was 55.8±21 ml/min/1.73m2 in patients with CKD and 87.3±13 ml/min/1.73m2 in patients without CKD according to the CKD-EPI formula. There was no significant eGFR decline in either of the groups during follow up. Office and 24-h systolic and diastolic BP were significantly reduced from baseline in patients with or without CKD at all time points after RDN (all p<0.01). There was no significant difference in the reduction of 24h, day- and nighttime ABP between the 2 groups at any time point (see table below). In addition to 24h baseline systolic ABP we identified several predictors (all p < 0.05): patients with a high baseline office heart rate (HR), without T2D, without diuretic medication and current smokers were more likely to be responders. With exception of rare local adverse events (e.g. haematoma at the puncture site), we had no safety signals, especially in our patients with CKD. Conclusions: According to our single center experience, we observed a similar reduction in 24-h, day and nighttime ambulatory BP as well as in office BP in patients with and without CKD at any time point up to 12 months. We conclude that RDN is an effective and safe treatment option for patients with arterial hypertension and CKD.

SKIN SODIUM CONTENT AS A PREDICTOR OF BLOOD PRESSURE RESPONSE TO RENAL DENERVATION

Objective: In patients with treatment resistant hypertension (TRH), renal denervation (RDN) emerged as an adjacent therapeutic option. It has been detected that patients with TRH have elevated Sodium (Na) content in muscle and skin. This analysis aimed at evaluating whether tissue Na content predicts blood pressure (BP) response after RDN. Design and method: Radiofrequency device based endovascular RDN was performed in 53 patients with uncontrolled TRH (office BP> = 140/90 mmHg and diagnosis confirmed by 24-h ambulatory BP monitoring) in our certified RDN center. Office and 24-h ambuatory BP were measured at baseline and after 6 months. To assess tissue Na content 23Na-MRI was performed at baseline prior to RDN. We splitted the study cohort based on the median systolic 24-h ambulatory BP reduction after 6 months into responders and non-responders and compared tissue Na content and baseline characteristics between these groups. The study was registered at http://www.clinicaltrials.gov (NCT01687725). Results: 53 patients were followed up for at least 6 months. Office systolic and diastolic BP were reduced by -12.9±21.1 mmHg and -7.7±12.5 mmHg and 24-h ambulatory systolic and diastolic BP were reduced by -8.6±14.0 mmHg and -4.7±9.5 mmHg after 6 months. Responder could be characterized as patients with low tissue sodium content in skin, more female patients, patients with aldosteron-antagonists, high baseline 24-h night-time heart rate and high LDL-cholesterol (see table, only p<0.10 are shown). This results remained significant after adjustment for baseline 24-h SBP. Similar results were obtained if the two groups were created based on the median of 24-h day-time and night-time BP reduction after 6 months. Conclusions: We identified Na in skin, sex, 24-h night-time heart rate, aldosterone antagonists and LDL-cholesterol as predictors of the systolic BP response. We conclude that 23Na-MRI may assist to select patients with uncontrolled TRH who will have a clinically meaningful BP reduction following RDN treatment.

DASH VS. MEDITERRANEAN DIET ON A SALT RESTRICTION BACKGROUND IN ADULTS WITH HIGH NORMAL BLOOD PRESSURE OR GRADE 1 HYPERTENSION: A RANDOMIZED CONTROLLED TRIAL

Objective: Non-pharmacological measures are recommended as the first-line treatment for individuals with high-normal blood pressure (BP) or mild hypertension. Studies directly comparing the BP effects of the Dietary Approaches to Stop Hypertension (DASH) vs. the Mediterranean diet (MedDiet) on a salt restriction background are currently lacking. Thus, our purpose was to assess the BP effects of a 3-month intensive dietary intervention implementing salt restriction either alone or in the context of the DASH, and the MedDiet compared to no/ minimal intervention in adults with high normal BP or grade 1 hypertension. Design and method: We randomly assigned never drug-treated individuals to a control group (CG, n = 60), a salt restriction group (SRG, n = 60), a DASH diet with salt restriction group (DDG, n = 60), or a MedDiet with salt restriction group (MDG, n = 60). The primary outcome was the attained office systolic BP difference among the randomized arms at the end of the study. Results: A total of 240 patients were enrolled, while 204 (85%) completed the study. According to the intention-to-treat analysis, compared to the CG, office and 24h ambulatory systolic and diastolic BP were reduced in all intervention groups. A greater reduction in the mean office systolic BP was observed in the MDG compared to all other study groups (MDG vs. CG: mean difference = -15.1 mm Hg; MDG vs. SRG: mean difference = -7.5 mm Hg, and MDG vs. DDG: mean difference = -3.2 mm Hg, all P-values < 0.001). The DDG and the MDG did not differ concerning the office diastolic BP and the 24h ambulatory systolic and diastolic BP; however, both diets were more efficient in BP-lowering compared to the SRG. Conclusions: On a background of salt restriction, the MedDiet was superior in office systolic BP-lowering, but the DASH and MedDiet reduced BP to an extent higher than salt restriction alone. Registration number: NCT05669404

IMPACT OF CELIPROLOL THERAPY ON BLOOD PRESSURE AND HEART RATE IN PATIENTS WITH VASCULAR EHLERS-DANLOS SYNDROME

Objective: Vascular Ehlers-Danlos syndrome (vEDS) is an inherited connective tissue disorder characterized by arterial fragility. Celiprolol is a beta1-adrenoceptor antagonist with partial beta2 agonist activity that has been shown to reduce rates of vascular events in this setting, though the underlying mechanisms are not yet fully understood. Aim of the present study was to assess the impact of Celiprolol on blood pressure (BP) and heart rate (HR) in patients with vEDS. Design and method: Patients with genetically confirmed disease referred to our Institution between 2011 and 2022 were divided into two groups according to whether or not they were on Celiprolol therapy. The former were included if on Celiprolol at the dose of 400 mg daily for at least 12 months. Each participant underwent office blood pressure (BP) measurement, 24-h ambulatory BP monitoring (ABPM), and pulse wave analysis (PWA) of the radial artery with calculation of central pulse pressure (PP) and augmentation index (AIx). Results: Overall, 18 patients (11 females) were included. Mean age was 36 years and mean body mass index (BMI) was 22.1 kg/m2. Eleven patients were on Celiprolol therapy. No significant differences were found between groups in terms of age, sex, BMI, and presence of hypertension (p>0.05). Patients on Celiprolol therapy displayed higher values of systolic BP (SBP) (124 vs 113 mmHg; p = 0.128), diastolic BP (DBP) (76 vs 67 mmHg; p = 0.236), mean BP (92 vs 83 mmHg; p = 0.173), and HR at office BP measurement, as well as lower AIx (126 vs 140%; p = 0.176) at PWA, although the difference was not statistically significant. Similarly, no significant difference was found for all ABPM parameters (24-h, day-time, and night-time SBP, DBP, mean BP, and HR), as well as central SBP, central DBP, central mean BP, and PP at PWA between groups (p>0.05). Conclusions: Our study suggests little impact of Celiprolol therapy on both BP and HR in patients with vEDS, which hints additional mechanisms behind its protective effect in this clinical setting. Further studies on larger cohorts are needed to clarify these aspects.

RELATIONSHIPS OF OFFICE, AMBULATORY, AND HOME BLOOD PRESSURE WITH ORGAN INJURY BIOMARKERS

Objective: International guidelines recommend out-of-office blood pressure (BP) monitoring including ambulatory and home BP. Although the superiority of ambulatory and home BP is controversial, home BP is more prevalent in plactice and there is a gap with the guidelines. We assessed this issue by conducting the analysis of relationship of BP with clinical biomarkers. Design and method: We analyzed the relationship of office, ambulatory, and home BP with organ injury biomarkers including urine-albumin creatinine ratio (UACR), serum b-type natriuretic peptide (BNP), serum high-sensitive troponin T (hsTnT), echocardiographic left ventricular mass index (LVMI), and brachial-ankle pulse wave velocity (baPWV) in 1,172 outpatients who underwent both ambulatory and home BP measurements and examined serum and urine tests and others. Results: In the univariate analysis of Pearson's correlation, average of morning and evening home systolic BP (SBP) was strongly related with log-transformed BNP, log-transformed hsCRP, LVMI, and baPWV compared with 24-h ambulatory systolic BP (log-transformed UACR [n = 1432], r = 0.24 in home SBP versus r = 0.18 in ambulatory SBP, P = 0.17 in z-test for comparison of these correlations; log-transformed BNP [n = 1432], r = 0.17 vs. r = -0.04, P<0.01; log-transformed hsTnT [n = 1092], r = 0.19 vs. r = -0.03, P<0.01; LVMI [n = 1036], r = 0.23 vs. r = 0.10, P<0.01; baPWV [n = 1361], r = 0.31 vs. r = 0.08, P<0.01). In the multivariable linear regression models for log-transformed BNP, log-transformed hsTnT, and LVMI, the model-fit were improved when adding home SBP to the model including 24-h ambulatory SBP, but these relationships were not shown in vice versa. In addition, we also used Structural Equation Modeling for assessment of relationship of office, ambulatory, and home SBP with clinical biomarkers. Conclusions: Our findings suggested the superiority of home BP in the relationship with several biomarkers for hypertensive organ damage compared with ambulatory BP, which may provide a rationale for the management on hypertension using home BP monitoring in clinical practice conducted in many countries including Japan.

OFFICE BLOOD PRESSURE VARIABILITY AND INSTABILITY IN CHILDREN, ADOLESCENTS AND YOUNG ADULTS: ASSOCIATION WITH PRECLINICAL ORGAN DAMAGE

Objective: To evaluate the association of systolic blood pressure (SBP) variability and instability within a single office visit with preclinical target organ damage in young individuals. Design and method: Apparently healthy individuals aged 6-25 years referred for elevated blood pressure (BP) were subjected to triplicate office BP measurements in a single visit and 24h ambulatory BP monitoring. SBP variability and instability were quantified using (i) standard deviation (SD) (ii) coefficient of variation (CV) (iii) average real variability (ARV) (iv) maximum office SBP (v) maximum-minimum office SBP difference (MMD) (vi) ratio of difference between 1st-3rd measurement to the average office SBP (Relative change). Preclinical organ damage was evaluated by (i) carotid intima-media thickness (cIMT), (ii) carotid-femoral pulse wave velocity (PWV; Complior device), and (iii) echocardiographic left ventricular mass index (LVMI). Results: 301 individuals were analyzed (mean age 13.8±3.7 years, 66.8% males, BMI z-score 1.12±0.95, average office BP 122.6±16.9/72.5±10.7 mmHg, 24h ambulatory BP 119.1±11.4/67.8±6.8 mmHg). LVMI measurements were available in 258 participants, IMT in 208 and PWV in 60. LVMI, IMT and PWV were associated with office SBP (r = 0.30/0.23/0.42, respectively, p< = 0.001), 24h ambulatory SBP (r = 0.35/0.33/0.48, p< = 0.001) and maximum office SBP (r = 0.31/0.30/0.41, p< = 0.001). LVMI and IMT were associated with SD (r = 0.14/0.15, p<0.05) and MMD (r = 0.13/0.15, p<0.05), while IMT and PWV with age (r = 0.31/0.38, p<0.001). Other indices of variability were not associated with indices of organ damage. In stepwise multivariable linear regression models (independent variables: age, sex, BMI z-score, office SBP, 24h ambulatory SBP, maximum office SBP, SD, MMD), LVMI was determined by BMI z-score and 24h ambulatory SBP, IMT by age, male sex and 24h ambulatory SBP, and PWV by 24h ambulatory SBP. Conclusions: These results suggest that in young individuals the variability and instability of office SBP within a single visit are not associated with preclinical organ damage.

EXERCISE THERAPY IN PATIENTS WITH ARTERIAL HYPERTENSION: A SYSTEMATIC REVIEW WITH META-ANALYSIS

Objective: High grade evidence supports exercise as a key therapy in the prevention and management of hypertension. Yet, the lack of a meta-analysis on the effects of exercise on ambulatory blood pressure monitoring (ABPM) in patients with hypertension was identified as an important research gap in the 2022 consensus document from the European Association of Preventive Cardiology and the ESC council on Hypertension. Therefore, we performed a meta-analysis to investigate the effects of exercise on blood pressures measured by means of ABPM, in patients with arterial hypertension or high-normal blood pressure (BP). Design and method: A systematic literature search was performed in three databases from inception to October 2021. Randomized controlled trials involving exercise training of at least 4 weeks, in adults with a high-normal BP or arterial hypertension, were included. Trials had to report data on daytime, nighttime or 24-h ambulatory systolic blood pressure (SBP) and/or diastolic blood pressure (DBP). Primary outcomes were changes in 24h, daytime and nighttime ABP. Pooled effect sizes are reported as weighted mean with 95% confidence intervals (CI). Results: We included 24 trials, involving 23 aerobic training interventions and 4 resistance exercise interventions. A total of 1668 participants were included: 942 in exercise groups, 726 as controls. Table 1: Pooled effect size, 95% CI and p-value of different exercise types on 24h, daytime and nighttime BP: Only 67 participants and 35 controls were included in resistance exercise protocols. In this subpopulation, results for 24h, daytime or nighttime BP were insignificant (p>0.05). Funnel plots for 24h, daytime and nighttime BP did not show any significant publication bias. Conclusions: Exercise therapy reduces 24h BP in patients with arterial hypertension or high normal blood pressure. The effect is more pronounced on daytime than on nighttime BP. The results of this meta-analysis are mostly driven by trials examining aerobic exercise. More trials are needed on the effect of resistance exercise on ABPM.

FACTOR ASSOCIATED WITH HYPERURICEMIA DEVELOPMENT DURING A 25 YEARS FOLLOW-UP: THE PAMELA STUDY

Objective: HyperUricemia (HU) has been associated with future fatal and non fatal CV events as well as with hypertension and metabolic syndrome development. However, only few data exist regarding the change in Uric Acid (UA) and the development of HU during a population follow-up. In particular, no study analyzed the variations during a very long follow-up. The present study was aimed at evaluating the factors associated with UA changes and HU development during a 25-years follow-up in the PAMELA study. Both the classic cut-off for hyperuricemia and the newly one identified by the Uric Acid Right for Heart Health (URRAH) study were used to define HU. Design and method: We analyzed data collected in 561 subjects of the Pressioni Arteriose Monitorate E loro Associazioni (PAMELA) study with available SUA who complete the 3rd wave study (mean follow-up time 25.2 ± 0.5 years). The classic cut-off of 6/7 mg/dL (females and males respectively) and URRAH one (5.1/5.6 mg/dL for females and males) were used for HU definitions. Results: Mean UA value during follow-up increase from 4.7 ± 1.1 to 5.0 ± 1.2 mg/dL (p < 0.001) with a mean increase of 0.3 ± 1.1 mg/dL. UA changes significanlty correlated with baseline UA (r = -0.39, p < 0.001) and creatinine (r = -0 - 21, p < 0.001). With the classic cut-off (6/7 mg/dL) 9.1% of the subjects develop HU and this was associated at the multivariate model with age, sex (male), baseline diastolic Blood Pressure (BP) (OR 1.038, p = 0.02) and UA (OR 2.62, p < 0.001). With the new URRAH cut-off 19.1% of the subjects develop HU. At the multivariate model variables associated were gender (male) and baseline 24h systolic BP (OR 1.05, p < 0.001), tryglicerides (OR 1.01, p = 0.01) and UA (4.99, p < 0.001). Conclusions: The present study provide evidence that in the PAMELA study during the 25 year follow-up there is a progressive increase in UA. Baseline UA is the most important factor associated with HU development. However, also age, gender, triglycerides and BP could help to identify subjects that most probably will develop HU.

APPLICABILITY OF THE SPRINT TRIAL IN A REAL WORLD SAMPLE OF HYPERTENSIVE OLDER ADULTS

Objective: The SPRINT trial demonstrated the benefits of intensive blood pressure (BP) control in older hypertensive adults, including frailer patients. However, how those results can be applied in the geriatric population remains doubtful, due to the highly selective inclusion criteria and low levels of clinical frailty in the aforementioned series. This study aimed to assess the applicability of SPRINT inclusion criteria in a real world sample of hypertensive older adults and analysed the association between BP and functional decline by SPRINT eligibility. Design and method: We applied SPRINT inclusion and exclusion criteria to a sample of hypertensive patients aged 75 or older, evaluated at the Hypertension and Memory Clinics of the Geriatric Department of Careggi Hospital, Florence. Cox analysis was used to test the association between BP and functional decline (according to Barthel Index) by SPRINT eligibility. Results: Among 123 patients (mean age 81, 59% women), only 39 (32%) complied with the SPRINT inclusion criteria. Frailty prevalence was found to be significantly higher in the ineligible group (46% vs 26%, p = 0.028), along with worse physical performance (reduced walking speed 43% vs 22%, p = 0.027) and disability either in basic (25% vs 5%, p = 0.009) or instrumental activities of daily living (61% vs 33%, p = 0.005). Moreover, they had a higher comorbidity burden (median Charlson Index 5 [4 - 6] vs 4 [3 - 5], p < 0.001), whereas there was no tangible difference between BP values in the two subgroups. At 13 months, ineligible subjects experienced significantly higher incidence of functional decline (48% vs 21%, p = 0.012). In age- and sex-adjusted Cox analysis, ambulatory BP was associated with functional decline only in eligible subjects (24h-systolic BP HR 1.193, 95% CI 1.009 - 1.411). Conclusions: In a real world sample of hypertensive older adults, only one third of subjects complied with the SPRINT inclusion criteria. Higher levels of frailty and disability were observed in ineligible subjects, in whom BP values seem to have a limited prognostic impact.

EARLY MORNING HEMODYNAMIC CHANGES AND LEFT VENTRICULAR HYPERTROPHY AND MORTALITY IN HEMODIALYSIS PATIENTS

Objective: Amplified early morning increase in BP, a phenomenon accompanied by a parallel rise in heart rate (HR), is a marker of high cardiovascular risk in the general population. The early morning changes in these parameters have not been investigated in the hemodialysis population. Design and method: In a pilot, single center, study including a series of 58 hemodialysis patients we measured the pre-awakening BP and HR surges and the nocturnal dipping of the same parameters as well as other established indicators of autonomic function (weighted 24h systolic BP and HR variability) and tested their relationship with the left ventricular mass index (LVMI) and with the risk of death over a median follow up of 40 months. Results: The pre-awakening HR surge (r = -0.46, P = 0.001) was inversely associated with LVMI and the risk of death [HR (1 unit): 0.89, 95% CI: 0.83-0.96, P = 0.001] while the corresponding BP surge largely failed to associate with these outcomes. The link between the pre-awakening HR surge with LVMI and death was robust and largely independent of established risk factors in the hemodialysis population, including the nocturnal dipping of BP. Weighted 24h systolic BP and HR variability did not correlate with LVMI (all P>0.11) nor with the risk of death (P>0.11) and these parameters were also independent of the nocturnal dipping of systolic BP and HR. Conclusions: This pilot study suggests that the low early morning changes in HR, likely reflecting enhanced sympathetic activity, entail a high risk for LVH and mortality in the hemodialysis population.

Long-term safety and efficacy of renal sympathetic denervation in atrial fibrillation: 3-year results of the AFFORD study

BackgroundAtrial fibrillation (AF) is the most common sustained arrhythmia which has been associated with increased sympathetic nervous system activity and hypertension. Recent evidence indicated that renal sympathetic denervation (RDN) could safely contribute to an improvement in AF burden.ObjectiveTo investigate the long-term safety and efficacy of radiofrequency RDN in hypertensive patients with symptomatic AF.MethodsThis pilot study included patients with symptomatic paroxysmal or persistent AF (European Hearth Rhythm Association class ≥ II) despite optimal medical therapy, office systolic blood pressure (BP) ≥ 140 mmHg and ≥ 2 antihypertensive drugs. AF burden was measured using an implantable cardiac monitor (ICM), implanted 3 months prior to RDN. ICM interrogation and 24-h ambulatory BP monitoring were performed at baseline and at 3/6/12/24/36 months post RDN. The primary efficacy outcome was daily AF burden. Statistical analyses were performed using Poisson and negative binomial models.ResultsA total of 20 patients with a median age [25th–75th percentiles] of 66.2 [61.2–70.8] years (55% female) were included. At baseline, office BP ± standard deviation (SD) was 153.8/87.5 ± 15.2/10.4 mmHg, while mean 24-h ambulatory BP was 129.5/77.3 ± 15.5/9.3 mmHg. Baseline daily AF burden was 1.4 [0.0–10.9] minutes/day and throughout a 3-year follow-up period, no significant change was observed (− 15.4%/year; 95% confidence interval (CI) − 50.2%, + 43.7%; p = 0.54). The number of defined daily doses of antiarrhythmic drugs and antihypertensive drugs remained stable over time, while mean 24-h ambulatory systolic BP decreased with − 2.2 (95% CI − 3.9, − 0.6; p = 0.01) mmHg/year.ConclusionsIn patients with hypertension and symptomatic AF, stand-alone RDN reduced BP but did not significantly reduce AF burden up until 3 years of follow-up.Graphical abstract

Exercise reduced the concentration of an inflammatory makers without modulating the levels of epigenetic marker potentially involved in hypertension: a preliminary study

Abstract Epigenetic mechanisms such as histone acetylation status mediated by HAT and HDAC2 enzymes play a central role in the pathophysiology, etiology, and progression of hypertension. The anti-inflammatory effects of physical exercise may be related to the modulation of histone acetylation status, which may alter the epigenome, providing therapeutic benefits for hypertensive individuals. To investigate the effects of an exercise training protocol on epigenetic parameters (HAT activities and HDAC2 concentrations), inflammatory markers (interleukin (IL)-10, tumour necrosis factor (TNF)-α, and C-reactive protein (CRP)), and cardiopulmonary fitness parameters (VO2peak, ambulatory blood pressure, NOx, endothelin 1 (ET-1), flow-mediated dilation, high density lipoprotein (HDL), and triacylglycerol levels) in treated hypertensive patients. Nine hypertensive patients aged 30-59 years underwent 12 weeks of strength or aerobic exercise 3 times a week. Physical fitness, 24-h blood pressure (systolic and diastolic), flow-mediated vasodilation, blood lipid profile analysis, and biomarkers were assessed before and after the intervention. No alterations were found in epigenetic parameters since HAT activities and HDAC2 concentrations remained unchanged after the intervention. Significant increases were found in VO2peak (pre: 29.1±6.3 and post: 31.5±6.3, P=0.021) and HDL (pre: 41.4±9 and post: 46.8±9.5, P=0.003). Furthermore, a significant reduction was seen in 24-h systolic and diastolic blood pressure, respectively: (pre: 119.1±5.6 and post: 114.4±4.5, P=0.6; pre: 73.9±4.1 and post: 70.5±4.2, P=0.4) and in CRP (pre: 2.4±1.4; post: 1.2±0.7*, P=0.03). Lastly, no alterations were found in IL-10 and TNF-α. In treated hypertensive individuals undergoing 12 weeks of exercise training VO2peak, 24 h blood pressure, HDL, and CRP improved. However, changes were not found in concentrations and the activity of HDAC2 and HAT, respectively.

Relationship between clinic and ambulatory blood pressure and mortality: an observational cohort study in 59 124 patients

Ambulatory blood pressure provides a more comprehensive assessment than clinic blood pressure, and has been reported to better predict health outcomes than clinic or home pressure. We aimed to examine associations of clinic and 24-h ambulatory blood pressure with all-cause and cardiovascular mortality in a large cohort of primary care patients referred for assessment of hypertension. We did an observational cohort study using clinic and ambulatory blood pressure data obtained from March 1, 2004, to Dec 31, 2014, from the Spanish Ambulatory Blood Pressure Registry. This registry included patients from 223 primary care centres from the Spanish National Health System in all 17 regions of Spain. Mortality data (date and cause) were ascertained by a computerised search of the vital registry of the Spanish National Institute of Statistics. Complete data were available for age, sex, all blood pressure measures, and BMI. For each study participant, follow-up was from the date of their recruitment to the date of death or Dec 31, 2019, whichever occurred first. Cox models were used to estimate associations between usual clinic or ambulatory blood pressure and mortality, adjusted for confounders and additionally for alternative measures of blood pressure. For each measure of blood pressure, we created five groups (ie, fifths) defined by quintiles of that measure among those who subsequently died. During a median follow-up of 9·7 years, 7174 (12·1%) of 59 124 patients died, including 2361 (4·0%) from cardiovascular causes. J-shaped associations were observed for several blood pressure measures. Among the top four baseline-defined fifths, 24-h systolic blood pressure was more strongly associated with all-cause death (hazard ratio [HR] 1·41 per 1 - SD increment [95% CI 1·36-1·47]) than clinic systolic blood pressure (1·18 [1·13-1·23]). After adjustment for clinic blood pressure, 24-h blood pressure remained strongly associated with all-cause deaths (HR 1·43 [95% CI 1·37-1·49]), but the association between clinic blood pressure and all-cause death was attenuated when adjusted for 24-h blood pressure (1·04 [1·00-1·09]). Compared with the informativeness of clinic systolic blood pressure (100%), night-time systolic blood pressure was most informative about risk of all-cause death (591%) and cardiovascular death (604%). Relative to blood pressure within the normal range, elevated all-cause mortality risks were observed for masked hypertension (HR 1·24 [95% CI 1·12-1·37]) and sustained hypertension (1·24 [1·15-1·32]), but not white-coat hypertension, and elevated cardiovascular mortality risks were observed for masked hypertension (1·37 [1·15-1·63]) and sustained hypertension (1·38 [1·22-1·55]), but not white-coat hypertension. Ambulatory blood pressure, particularly night-time blood pressure, was more informative about the risk of all-cause death and cardiovascular death than clinic blood pressure. Spanish Society of Hypertension, Lacer Laboratories, UK Medical Research Council, Health Data Research UK, National Institute for Health and Care Research Biomedical Research Centres (Oxford and University College London Hospitals), and British Heart Foundation Centre for Research Excellence.