Ambulatory Blood Pressure Research Articles

Effect of nebivolol monotherapy or combination therapy on blood pressure levels in patients with hypertension: an updated systematic review and multilevel meta-analysis of 91 randomized controlled trials.

To systematically appraise and summarize the available evidence from published randomized controlled trials considering the effect of nebivolol on blood pressure in patients with hypertension. 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. In total, 7,737 participants with hypertension, who were treated with nebivolol, were analyzed across 91 RCTs. 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, resulted 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 the 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 comparators, there was no significant difference in systolic BP reduction, but a significant reduction in diastolic BP favoring nebivolol. Based on moderator analyses, the impact of nebivolol on the pooled estimates remained independent of the dose of nebivolol, age, male sex, trial duration, body mass index (BMI), baseline diabetes, heart failure, and baseline systolic and diastolic BP. Nebivolol, compared to placebo, showed a significant BP reduction and was non-inferior to other active comparators in terms of BP reduction.

Detection of hypotension in patients with syncope: combined tilt test and ambulatory blood pressure monitoring strategy in clinical practice

Abstract Both ambulatory blood pressure monitoring (ABPM) and Tilt Test (TT) (a provocation method), can identify the hypotensive component that predisposes to syncope. Objective 1)To establish a) the prevalence of confirmed hypotension (CHp) with both methods; b) the concordance between them. Methods Patients (pts) ≥18 years with syncope for whom it was decided to perform a TT were included. TT was performed for 45 min at 75 degrees. On a different day, within 15 days, an ABPM was performed (≥70 % adequate readings). Criteria: CHp: In TT: TT(+) or detection of systolic blood pressure (SBP) ≤ 100 mmHg during the study resulting from a drop from baseline; in ABPM: SBP ≤ 100 mmHg resulting from a drop ≥ 20 mmHg from the previous one. Only the awake periods were considered. Results 61 pts (age= 62.5±16.8, female= 39 (64%); antihypertensive medications= 35 pts (57%); Cardiovascular history, except isolated hypertension= 29 pts (47%). The reported number of episodes was 4±4.4 (median=2). Syncope was post-prandial in 25 pts (41%) and probable reflex by the description in 28 pts (46%). CHp during syncope was confirmed in 25 pts during TT and in 1 pt during ABPM. Positive responses to TT were: vasodepressor in 14 pts, mixed in 10 pts and disautonomic pattern in 1 pt. Average 24 h in ABPM was above 135 mmHg in 10 pts (16%). Seventy-nine per cent of the population (48 pts) presented ≥ 2 falls ≥20 mmHg of SBP during the waking period. SBP ≤ 100 mmHg constituted ≥ 20% of awake measurements in 10 pts (16%). A post-prandial fall in SBT ≥ 20 mmHg was detected in 24 patients (39%). Of these, in 8 (13%), the achieved SBP was ≤ 100 mmHg. Table 1 shows the prevalence for CHp with both methods. Table 2 shows the concordance between TT and ABPM. CHp was detected by TT or ABPM in 48 pts, i.e 79% of the population. Both studies were concordant in 32 pts (52%) (Cohen's kappa coefficient: 0.04). CHp was identified in 28% of pts only by TT and in 20% only by ABPM. Conclusion CHp was detected in ¾ of this population using a combined TT and ABPM strategy. They were complementary not only to establish a diagnostic suspicion, but also to guide the therapeutic management of these patients.CHp PrevalenceTT and ABPM Concordance

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.

Association between the cumulative excessive systolic blood pressure and left ventricular mass index

Abstract Background Ambulatory blood pressure (ABP) has been increasingly adopted in day-to-day clinical practices. Although clinicians can access an enormous amount of information regarding an individual’s blood pressures (BPs) through the ABP monitoring (ABPM), to date, only the mean BP is utilized as the diagnostic threshold of hypertension and the therapeutic target for BP control and no other indices were widely used to assess the burdens of high BP in the ABPM. Because elevated systolic BPs (SBPs) cumulatively damage the myocardium and induce hypertrophy and fibrosis, we hypothesized that the summated value of BP readings beyond a target level may be the better indicator of the overall BP loads than the mean BP value. Methods The Korean ABP registry is a multicenter prospective longitudinal cohort study performed in outpatients with hypertension. Among 5,965 patients enrolled in the registry, 951 patients with valid ABPM records and appropriate echocardiography measurements included in the study. The left ventricular mass (LVM) was normalized using the height2.7(m) (LVM index [LVMIH2.7] = LVM/Height2.7). The cumulative excessive SBP CE-SBP) was defined as the summation of the products of excessive SBPs (≥135 mmHg during wake, ≥10 mmHg during sleep) and the durations of the excessive SBP (Figure 1). Results The CE-SBP was non-linearly associated with both the office SBP and the mean SBP, but the association strength was much greater with the mean SBP than with the office SBP (R2=0.902 vs. R2=0.430). In linear regression models, the association of the CE-SBP with the LVMIH2.7 (R2=0.112 [0.074-0.149]) was greater than that of the office SBP (R2=0.072 [0.040-0.103]), the mean SBP (R2=0.082 [0.049-0.116]) or the mean SBP during sleep (R2=0.99 [0.063-0.134]). Non-linear regression models using restrictive cubic spline fits also showed that the association strength was greater with the CE-SBP (R2=0.117 [0.078-0.155]) than with the office SBP, mean SBP or mean SBP during sleep (Figure 2). Left ventricular hypertrophy (LVH) defined as the LVMIH27 ≥54 g/m2.7 was better predicted with the CE-SBP than with the other SBPs. The association between the CE-SBP and LVMIH27 was stronger in the patients not taking antihypertensive medications (R2=0.121) and strongest in those with the non-dipper pattern (R2=0.125). Combination with the variability indices (successive variation and average real variability) during sleep or the maximum SBP during sleep significantly improved the association strength of CE-SBP with LMMIH27, whereas the combination with the mean SBP or the variability indices during the entire period did not, in the linear models. Conclusion The CE-SBP was more strongly associated with the LVMIH27 than the office SBP and the mean SBP in the ABPM. This result suggests that the CE-SBP may be the better indicator of overall BP loads than the office SBP or the mean SBP in the ABPM, in patients with hypertension.Figure 1Figure 2

To compare 24 hour blood pressure values of a conventional 24 hours ambulatory blood pressure device versus a wristband using an artificial intelligence algorithm based on photophletysmography

Abstract Background Ambulatory Blood Pressure Monitoring is of high added value in determining blood pressure, but also highly relevant quantitatively, as hypertension is the single most common medical condition. Unfortunately, practical and qualitative limitations are numerous. Purpose To determine the accuracy of a novel wrist-worn cuff-calibrated photoplethysmography (PPG)-based remote patient monitoring device versus ambulatory blood pressure monitoring (ABPM). Methods The single-center prospective study included 40 adult patients with standard 24-hour ABPM with a 30-minute measurements. Participants used a wrist-worn PPG device during the ABPM period. Measurements of the average difference and standard deviation (SD) for the full 24-hour period as well as for awake and asleep periods were compared. Differences in awake-asleep BP change between the investigational and reference device were described for all, and per nighttime BP dipper category. And also, investigational BP monitoring accuracy under motion will be visualised. Results During the 24-hour period the absolute difference in average SBP and DBP was 3.65 (SD±4.57) and 2.98 (SD±3.91), respectively. Similar results were found for the subsets of day- and nighttime determinations. The absolute difference in average awake-asleep BP change was 2.36 (SD ± 2.40) for SBP and 2.17 (SD ± 2.13) for DBP. Comparable absolute differences were present within each of the nighttime dipper categories. The performance of the investigational device remained stable during motion. Conclusions This study demonstrates initial evidence supporting the accuracy of the evaluated wrist-worn PPG-based device in measuring 24-hour as well as day- and nighttime BP. In the average difference and SD remained within ISO-81060-2:2018 cut-off values from recent ESH guidelines. Therefore, the presented method can provide an accurate and more patient friendly alternative to ABPM.

Evaluation of renal functional reserve in patients with preserved renal function and coronary microvascular disease

Abstract Background/introduction Renal Functional Reserve (RFR) stands as a subject of significant scientific discussion,holding promise as a diagnostic tool for early detection of subclinical renal disorders. Literature establishes a link between chronic kidney disease & cardiovascular disease (CVD). Purpose This study aims to assess RFR in patients with coronary microvascular dysfunction (CMD), while maintaining preserved renal function (eGFR≥60ml/min/1.73m2 by CKD-EPI criteria)&proteinuria<400mg/24hr. The investigation seeks to provide insights into the nuanced relationship between renal function&CMD, offering potential early indicators of CVD. Methods This is a single-center, prospective study enrolling patients with CMD. In the absence of significant coronary artery disease, functional coronary circulation assessment was performed. Coronary flow reserve (CFR) & index of microvascular resistance (IMR) were measured invasively with bolus thermodilution technique. In all participants, RFR was estimated by endogenous creatinine clearance after oral protein load (cooked meal, 1.2gr/kg). Normal RFR was defined as≥30 ml/min/1.73m2. Also, patients with CMD were offered 24-hour Ambulatory Blood Pressure Monitoring (ABPM). Results A total of 25 participants have been enrolled so far in study: 11 without CMD - control group [7 female, 64%, mean age: 52.9±8.8 years) & 14 with CMD – CMD group (11 female, 79%, mean age: 53.5±10,3 years). CMD patients were classified into 2 groups, structural & functional endotype (CFR<2.5 & IMR≥25 were considered abnormal). The RFR value for CMD & control group is 7.4±6.3 vs 36.3±5.8 ml/min/1.73m2 respectively (p<0.05). This difference between groups remained statistically significant after controlling for confounding factors. It was found that RFR value for functional & structural CMD endotype was 3.8±2.6 & 9.6±7,2 ml/min/1.73m2 respectively (p=0.06). Furthermore, no statistical significance was found between RFR and IMR, CFR indices. According to data from ABPM, there were no significant differences in ambulatory blood pressure (both systolic and diastolic) between the two endotypes of CMD, as well as no relationship with RFR was observed. However, the proportion of non-dipping BP pattern was significantly higher in functional CMD endotype (p<0.05). It was not found correlation between RFR & non-dipping phenotype. Conclusions Impaired RFR is evident across all individuals experiencing microvascular angina. Furthermore, those with functional CMD exhibit a diminished RFR when compared with their counterparts with structural CMD. RFR does not exhibit a correlation with blood pressure levels or the absence of a nocturnal dipping pattern. In light of the hypothesis asserting that appraising renal functional reserve serves as an early diagnostic measure for subclinical renal disorders, promptly recognizing individuals with distinct phenotypes could facilitate tailoring therapeutic interventions on an individual basis.Functional Coronary AngiogramCMD group baseline characteristics

The effect of spironolactone versus eplerenone on blood pressure targets in resistant hypertension patients

Abstract Objective to evaluate different effects on blood pressure (BP) control in two treatment options spironolactone (SPIR) versus eplerenone (EPL) as an add-on therapy in resistant hypertensive (RAH) patients. Design and methods: We studied 208 patients with true RAH confirmed by the office and ambulatory BP monitoring (ABPM) despite the use of 3 antihypertensive medications including a calcium channel blocker, a blocker of the renin-angiotensin system, and a thiazide diuretic with maximally tolerated doses for at least 3 months. Patients were randomized into 2 groups throughout 12 weeks of once-daily treatment with SPIR (25–50 mg) or EPL (25-50 mg) in addition to their baseline triple-combination and then rotated with drugs. BP was measured in the office and by ABPM. Changes in laboratory tests were also studied. The predictive values of plasma aldosterone, active renin concentration (ARC), aldosterone-renin ratio (ARR), and serum potassium were analyzed to determine the antihypertensive response. Results There were no significant differences in the reduction of average office BP, average systolic 24-h, daytime, and nighttime BP by SPIR and EPL. SPIR reduced average diastolic 24-h BP by 7.3 mm Hg, diastolic daytime BP by 7.2 mm Hg, and diastolic nighttime BP by 7.5 mm Hg compared with a reduction of 5.6 mm Hg (P = 0.01), 5.6 mm Hg (P = 0.03) and 4.2 mm Hg (P = 0.0001) with EPL, respectively. Overall, 40.7 % RAH patients achieved targets of clinical BP and 24-h ABPM levels on SPIR and 33.3 % on EPL (Р = 0.002). After 12 weeks of treatment mean plasma potassium concentrations increased by 7.1 (P = 0.0001) on SPIR and by 5.0 % (Р = 0.0001) on EPL, but eGFR did not significantly change on the two drugs. Plasma aldosterone (β = 0.498, Р = 0.02) and ARC (β= -0.374, Р = 0.04) were predictors of the BP-lowering effect of SPIR and plasma aldosterone (β = 0.453, Р = 0.04) was a predictor of reduction BP for EPL in multivariate modeling. Breast pain or tenderness, changes in sex drive, and irregular menstrual cycles or spotting were more often by SPIR than by EPL (5.2 % vs 1.9 %, respectively, P = 0.04). Conclusions The greater antihypertensive effect of SPIR is related to aldosterone status, ARS level in resistant hypertension. EPL may be recommended for RAH patients who have high serum potassium levels that cannot tolerate spironolactone and for people with systolic resistant hypertension.

Masked hypotension in patients with heart failure

Abstract Background Hypotension limits the up-titration of guideline-directed medical therapies (GDMTs) and correlates with poor prognosis in patients with heart failure. The value of ambulatory blood pressure monitoring (ABPM) in heart failure patients and its association with GDMTs optimization and clinical outcomes were undetermined. Methods REM-HF (Risk Evaluation and Management in Heart Failure) is a multicenter, prospective observational cohort. Our study screened patients from REM-HF who were hospitalized for incident HF and newly initiated GDMTs between April 2018 and December 2022. Eligible participants conducted a 24-hour ABPM before discharge and were followed-up as the cohort routine. GDMTs target dose achievement and dose trajectories were assessed at 3-month visit. The primary outcome was a composite of all-cause mortality and heart failure readmission. Results On adjusted restricted cubic spline analysis, office SBP demonstrated a U-shape relationship with the primary outcome (P for nonlinearity=0.003), while 24-hour SBP was linear (P for nonlinearity=0.338). The risk-related threshold of ambulatory and office systolic hypotension was defined as corresponding SBP < 120 mmHg accordingly. Combining these two measurements together, we described three blood pressure status as sustained hypotension (s-hypo, both SBP < 120 mmHg), masked hypotension (m-hypo, 24h SBP < 120 mmHg while office SBP ≥ 120mmHg), and non-hypotension (n-hypo). Among the 491 patients included, 124 (25.3%), 151 (30.8%) and 216 (44.0%) had s-hypo, m-hypo, and n-hypo, respectively. The m-hypo group showed similar clinical features as the s-hypo subjects, including more serious left ventricle remodeling and worse cardiac function. After the GDMTs dose titration, either patients with s-hypo or m-hypo were as unlikely to achieve target dose as the non-hypotensives (OR for s-hypo 0.42, 95%CI 0.19-0.95, P=0.038; OR for m-hypo 0.39, 95%CI 0.19-0.80, P=0.011). During a median follow-up of 693 days, the adjusted risk of primary outcome was higher in the s-hypo group and m-hypo group compared with the non-hypo group (HR for s-hypo 2.47, 95%CI 1.54-3.96, P<0.001; HR for m-hypo 1.68, 95%CI 1.06-2.65, P=0.027). No significant differences were found in target dose achievement and clinical outcomes between the s-hypo and m-hypo groups. Conclusion Masked systolic hypotension can occur in nearly one-third of new-onset HF patients. Patients with m-hypo and s-hypo exhibit similar clinical characteristics, both associated with GDMTs intolerance and adverse outcomes, suggesting m-hypo deserves recognition as a discrete entity. ABPM provides a more comprehensive view of patients’ blood pressure status by identifying this population.

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.

Treadmill exercise test as a screening tool in the development of hypertension

Abstract Background Guidelines promote screening people with high normal BP for the presence of end-organ damage because their presence is associated with a 2- to 3-fold increase in the risk of CVD. Purpose Office blood pressure measurements may be unable to detect early subclinical cardiac damage of adverse prognostic significance in subjects with high normal blood pressure. Methods 100 consecutive subjects with high normal BP [systolic BP=130-139mmHg and/or diastolic BP=85-89mmHg] were examined for early signs of hypertension-mediated organ damage (HMOD). They underwent an echocardiographic study, a negative for ischemia treadmill exercise test (Bruce protocol) where the index SBP/MET-slope [(peak SBP—resting SBP)/(peakMET-1)] was used. Arterial stiffness was evaluated based on carotid-femoral pulse wave velocity (PWV). The sympathetic drive was assessed by MSNA. Follow-up was scheduled every 6 months for 3 consecutive years, where BP measurements were assessed in the office and with ambulatory BP monitoring (ABPM). All participants offered lifestyle advice to lower their BP. The endpoint was the development of HTN either with Office BP or ABPM. Results Of 100 subjects (54±8 years, 42 males, baseline office BP: 132/82 mmHg, 24-hour BP: 122/76 mmHg), 40 developed HTN in 3 years. 34 subjects developed Hypertensive Response to Exercise (HRE) (BP >210mmHg in men and >190mmHg in women) and all of them developed HTN. The SBP/MET-slope in future hypertensives was increased in all stages till peak exercise independently of sex type (stage1: 6.7vs4.9 p=0.049, stage2: 8.4vs4.8 p=0.001, peak: 6.7vs4.9, p=0.001). Their exercise capacity was reduced (10vs11.3METs, p=0.002) as well as their maximum exercise heart rate (156vs164, p=<0.0001). Those with HRE had higher 24hSBP (124vs121mmHg, p=0.009), Night SBP (117vs111mmHg, p<0.001), Day SBP (127vs124mmHg, p=0.012) Office Pulse Pressure (51vs47mmHg, p=0.01). Additionally, they had increased PWV (8.3vs7.5m/sec, p=<0.0001), MSNA levels (36vs28 bursts, p=<0.0001), LVMI (38vs34 gr/m2.7, p=0.02), and a statistically significant deterioration of 2021 CKD-EPI eGFR (90 vs 97 mL/min/1.73 m², p=0.02). All of them correlated with development of hypertension (p=0.002), while they did not differ regarding their metabolic profile at the follow-up. Conclusion Detecting exaggerated blood pressure response and specifically an increased SBP/MET-slope in the end of second stage of Bruce protocol at treadmill exercise test is associated with increased systemic vascular resistance and early subclinical HMOD which may upgrade an individual’s cardiovascular disease (CVD) risk as they progress to HTN indicating a need for instituting a BP-lowering strategy.

Combining fractional flow reserve and the index of microcirculatory resistance for prognosis prediction in renal artery stenosis interventions: a feasibility sub-study of FAIR-pilot trial

Abstract Background Interventional therapies for renal artery stenosis (RAS) was debatable in previous randomized trials. Fractional flow reserve (FFR), while useful in coronary interventions, does not assess microcirculatory status, which may be critical in RAS. The index of microcirculatory resistance (IMR) provides additional microvascular information, which has not been used in RAS patients. Purpose To investigate the feasibility of IMR measurement in RAS patients and the association with the outcome. Methods FAIR-pilot study is a multicenter pilot randomized controlled trial exploring the application of FFR to guide the renal artery stenting in patients with renovascular hypertension (NCT05732077). A pressure-temperature sensor guidewire was used to measure the IMR. To derive mean transit time at rest, thermodilution curves were obtained by 3 injections of 4 mL of room temperature saline down the renal artery. Hyperemia was induced using dopamine 50μg/kg bolus to the renal artery. The IMR was calculated as distal arterial pressure (Pd) x mean transit time during hyperemia (TmnH) (Figure 1). Prognostic evaluation was based on improvements in postoperative blood pressure, which was assessed using both ambulatory blood pressure monitor (ABPM) and anti-hypertensive medication number, along with renal function, as determined by the estimated glomerular filtration rate (eGFR). Results The IMR was measured among five patients enrolled in FAIR-pilot study. As shown in Table 1 and 2, stent implantation was conducted on five lesions across patients 1 to 4 based on renal FFR < 0.8, with each experiencing varying degrees of improved blood pressure control subsequently. Patient 5 did not receive a stent and was lost to follow-up. At three-month, the recorded decrease in systolic blood pressure ranged from a maximum of 34 mmHg to a minimum decrease of -6 mmHg among the four patients. The antihypertensive medication number showed a maximum reduction of 2 and no change as the minimum. We observed a correlation between baseline IMR and baseline renal function. No significant change in IMR was noted after interventional procedures. Preliminary findings suggest that IMR measurement is feasible in patients with RAS, while the ∆T (temperature change time) was very small, which potentially increasing the measurement bias. Conclusion The study suggests measuring IMR in patients with RAS is feasible and can offer information into the renal microvasculature. However, the small ∆T encountered during measurement may introduce increased bias, which should be considered when interpreting results.

Ventricular arrhythmia characteristics after left ventricular assist device implantation

Abstract Background Ventricular arrhythmia (VA) characteristics in patients with advanced heart failure (HF) and left ventricular assist devices (LVADs) are currently poorly studied. Methods Patients with advanced HF implanted with third-generation LVADs during 2019-2023 were enrolled, and six-month post-LVAD VA events were retrospectively analyzed. Baseline characteristics, 6-month VA events, Holter monitoring and ambulatory blood pressure were also analyzed. Post-LVAD VA events were categorized as new right bundle-branch block (RBBB) superiorly directed VA and prior VA recurrence. Results Fifty-four advanced HF patients (90.7% male, 50.0±13.7 years old) who underwent LVAD (CH-VAD: n=23; Evaheart2: n=10; Corheart6: n=21) were consecutively enrolled in this study. Twenty-two patients suffered post-LVAD VA events (15 new RBBB superiorly directed VA, 7 prior VA recurrence), and 94.4% of the patients were hemodynamically stable. A total of 46.3% of the patients presented with a 50% reduction in VA burden, and amiodarone use decreased from 25.9% to 16.7%. The nighttime mean arterial pressure (MAP) and maximum inferior venous cava (IVC) diameter had opposite predictive effects on the new RBBB VA, and the post-LVAD left ventricular ejection fraction (LVEF) was negatively correlated with the prior VA recurrence. Multivariate analysis revealed that a higher nighttime MAP/IVC ratio (OR 2.24, 95% CI 2.22-4.52; P=0.025) and a lower post-LVAD LVEF (OR 0.75, 95% CI 0.57-0.99; P=0.048) were independently related to the new RBBB superiorly directed VA and prior VA recurrence, respectively. Conclusion The overall VA burden decreased after LVAD implantation. Volume deficiency and poor post-LVAD cardiac function were associated with different VA patterns.Changes in VAs pre- and 6 monthsVA distributions of patients

Blood pressure and renal function changes in patients with severe chronic kidney disease undergoing radiofrequency renal denervation: 12 months outcomes from the Global SYMPLICITY Registry DEFINE

Abstract Background Radiofrequency renal denervation (RF RDN) lowers blood pressure (BP) in patients with uncontrolled hypertension (HTN). The impact of renal function on safety and efficacy of RDN is unknown. Purpose To assess BP and renal function in patients with HTN following RDN. Methods All patients treated with RF RDN (n=3332) from the observational Global SYMPLICITY Registry Denervation Findings in Real World (GSR DEFINE) were included. Patients were categorized into CKD stages by the corresponding estimated glomerular filtration rate (eGFR; mL/min/1.73m2): <45 (CKD stage 3b and higher; n=339), 45-59 (CKD stage 3a; n=467), ≥60 (CKD stage 2 and lower; n=2334). BP (office, 24h ambulatory BP), eGFR changes from baseline through 12 months were compared between groups. Comparisons between groups were made after adjusting for baseline BP and change in number of antihypertensive drug classes from baseline. Results At baseline, office systolic SBP (OSBP) in eGFR groups <45, 45-59, and ≥60 ml/min/1.73 m2 was: 164±25, 163±26 and 165±25 mmHg, respectively (p=0.083). 24-h ambulatory systolic BP (ASBP) was: 156±19, 153±20 and 154±19 mmHg, respectively (p=0.082). Mean eGFR was: 32.5±11.2, 53.6±4.4, and 86.8±18.6 ml/min/1.73 m2, respectively. A total of 1.1% of patients were on dialysis. Patients in eGFR group <45 ml/min/1.73 m2 were significantly older, had higher rates of ischemic heart disease, heart failure, diabetes, on more antihypertensive drug classes compared to higher eGFR groups. Patients were on 5.0±1.3, 4.6±1.3, and 4.5±1.4 antihypertensive drugs in eGFR <45, 45-59 and ≥60 ml/min/1.73 m2 groups, respectively (p<0.001). At 12 months, all had significant OSBP drop from baseline within the different eGFR groups (p<0.001). OSBP changed by -10.8±27.8, -10.5±25.9 and -14.7±26.6 mmHg in eGFR <45, 45-59 and ≥60 ml/min/1.73 m2 groups, respectively (adjusted p=0.095; Figure 1A). Similarly at 12 months, all patients had significant ASBP reductions from baseline across the eGFR groups (p<0.01). ASBP changed by -5.2±18.0, -6.9±18.8, and -8.5±18.8 mmHg in eGFR <45, 45-59 and ≥60 ml/min/1.73 m2 subgroups, respectively (adjusted p=0.16). At 12 months, eGFR did not significantly change from baseline in eGFR <45 and 45-59 ml/min/1.73 m2 groups (Figure 1B): 0.1±14.6 (p=0.92) and -0.6±12.8 ml/min/1.73 m2 (p=0.45), respectively. Estimated GFR changed from baseline by -5.6±15.5 ml/min/1.73 m2 in eGFR ≥60 ml/min/1.73 m2 group (p<0.001). Between group differences in eGFR changes were statistically significant (adjusted p<0.001), but by a numerically small difference. The no. of antihypertensive drug classes changed by -0.2±1.3, -0.1±1.0 and -0.1±1.0 in eGFR <45 and 45-59 ml/min/1.73 m2 groups, respectively. Conclusion Patients with uncontrolled HTN with different CKD severity including those with eGFR <45 ml/min/1.73 m2 had significant SBP reductions from baseline through 12 months, whilst renal function was preserved.Figure 1

Differential impact of clinic BP target on the prevalence and predictors of the masked uncontrolled hypertension and white-coat uncontrolled hypertension

Abstract Background Although intensive blood pressure (BP) control have been advocated, major clinical practices guidelines still recommend clinic BP (cBP) < 149/90 mmHg as the target for antihypertensive therapy. But, cBP targets could influence the prevalence and predictors of any hypertension phenotype. We investigated how different cBP targets impacted on the prevalence and predictors of masked uncontrolled hypertension (MUCH) and white-coat uncontrolled hypertension (WUCH) using the Korean Ambulatory Blood Pressure (KorABP) registry. Methods A multicenter prospective longitudinal cohort study was performed in outpatients with hypertension. Among 5,965 patients enrolled in the KorABP registry, 1,601 patients on antihypertensive medications with a valid ambulatory BP monitoring record were included in this study. Two different cBP targets, <130/80mmHg (intensive) and <140/90 mmHg (conventional) were investigated. Results Controlled ambulatory BP (aBP; <130/80 mmHg) was observed in 472 patients (29.5%). Controlled cBP was shown in 348 patients (21.7%) with the intensive cBP target and in 697 patients (43.5%) with the conventional cBP target. Controlled hypertension, WUCH, MUCH and uncontrolled hypertension were found in 294, 174, 54, and 1,075 patients with the intensive target and in 378, 94, 319 and 810 patients with the conventional target, respectively. Among the patients with controlled cBP, the prevalence of MUCH markedly decreased with the intensive target (15.5%), compared to the conventional target (45.8%). In contrast, among the patients with uncontrolled cBP, the prevalence of WUCH had only 3.8% increase with the intensive target (10.4%), compared to the conventional target (14.2%) (Figure 1). With the conventional target, 75.9% of patients with MUCH had cBP between 130/80 mmHg and 139/89 mmHg. The concordance between the controlled aBP and controlled cBP was higher with the intensive target than with the conventional target (Cohen’s κ 0.62 [0.58-0.67] vs. 0.46 [0.41-0.50]). The logistic models for MUCH included the left ventricular mass index and underuse of antihypertensive drugs (<2 types of drugs) as the common predictors of the both targets. With the conventional target, clinic systolic BP and diastolic BP were the strongest predictors of MUCH, but the cBP was not a predictor of MUCH with the intensive target. The logistic models for WUCH included beta-blocker use, increased heart rate and lower waist circumference and clinic systolic BP as the common predictors of WUCH with the both target. The logistic model for MUCH performed better with the conventional target, whereas the logistic model for WUCH performed better with the intensive target (Figure 2). Conclusion The use of the intensive cBP target (<130/80 mmHg) could reduce the prevalence of MUCH with minimal increase in the prevalence of WUCH and would provide the better assessment for the BP control status than the use of the conventional cBP target (<140/90 mmHg).Figure 1Figure 2

Circadian heart rate fluctuations predict 21-year cardiovascular and all-cause mortality in type 2 and type 1 diabetes

Abstract Background Alterations in circadian heart rate (HR) fluctuations have been associated with cardiovascular events in the general population. This study aimed at defining their long-term prognostic value for cardiovascular and all-cause mortality in patients with diabetes. Methods We examined a cohort of 349 patients with type 2 or type 1 diabetes (52% women, age 57.1±11.9 years, BMI 29.4±5.9 kg/m2, HbA1c 8.6±2.1%, 81% type 2 diabetes) who underwent 24h ambulatory blood pressure and HR monitoring (ABPM) and assessment of diabetic microvascular complications. The median standard deviation (SD) value of ABPM-derived HR measurements was used to define patients with low daily HR fluctuations (low 24h-HR SD), while a <10% decline in average night-time vs day-time HR identified patients with blunted nocturnal HR dip (n=107, 31%). The clinical features and time-dependent prognostic impact of these conditions were evaluated over a 21-year observational follow-up. Results Low 24h-HR SD and blunted nocturnal HR dip were associated with an adverse cardiometabolic risk profile and high prevalence of cardiac autonomic neuropathy and nephropathy. After 6,251 person-years of follow-up (21.0 [14.0-21.0] years), a total of 136 (39%) deaths occurred, of which 100 (68%) of cardiovascular cause. After adjustment for potential confounders, the low 24h-HR SD group had a higher risk for both cardiovascular (hazard ratio 1.99, 95% CI 1.29–3.06, p=0.002) and all-cause mortality (hazard ratio 1.50, 95% CI 1.03–2.18, p=0.033), compared with high 24h-HR SD. Consistently, patients with blunted nocturnal HR dip had a higher adjusted risk for cardiovascular (1.61, 95% CI 1.07–2.43, p=0.023) and all-cause mortality (1.61, 95% CI 1.11–2.34, p=0.012), compared with those with preserved nocturnal HR dip. Conclusions Impaired circadian HR fluctuations are frequent in patients with long-standing diabetes and are associated with microvascular disease and increased long-term cardiovascular and all-cause mortality. Identifying these conditions via 24h-ABPM may provide a cost-effective risk stratification tool in this high-risk population.Kaplan-Meier curves

Subgroup results from KARDIA-2: impact of demographic and baseline disease characteristics on zilebesiran response in patients with hypertension uncontrolled by a standard oral antihypertensive

Abstract Background Zilebesiran is an investigational RNA interference therapeutic targeting hepatic angiotensinogen synthesis. In KARDIA-1, a single subcutaneous (SC) dose of zilebesiran monotherapy significantly reduced 24-hr mean ambulatory and office systolic blood pressure (SBP) from baseline to Months 3 and 6 versus placebo. The Phase 2 KARDIA-2 study assessed efficacy and safety of zilebesiran with a standard oral antihypertensive in patients with uncontrolled hypertension. Purpose Uncontrolled hypertension is a leading cause of cardiovascular morbidity and mortality, and medication non-adherence affects blood pressure control. Developing effective, long-lasting treatments is crucial for patients with hypertension uncontrolled by standard therapy. Methods KARDIA-2 enrolled adults with mild-to-moderate hypertension who were untreated or receiving stable therapy with ≤2 antihypertensives. Patients discontinued prior antihypertensive medication and were randomized 10:7:4 to open-label, once-daily oral treatment with 40 mg olmesartan, 5 mg amlodipine, or 2.5 mg indapamide. After ≥4 weeks on protocol-specified medication, patients with a 24-hr mean ambulatory SBP of 130–160 mmHg were randomized 1:1 in a double-blind manner to a single SC dose of zilebesiran 600 mg or placebo as add-on therapy. The primary endpoint was change from baseline to Month 3 in 24-hr mean ambulatory SBP versus placebo for each group. Efficacy and safety were also assessed in pre-specified subgroups: age (<65; ≥65 years), sex, race (Black; other), baseline 24-hr mean ambulatory SBP (<145; ≥145 mmHg), and baseline estimated glomerular filtration rate (≥60; <60 mL/min/1.73m2). Results The primary analysis included 667 patients (median age [range] 59 [27–75] years; 57% male, 28% Black). At Month 3, least-squares mean differences (LSMD) (95% confidence interval [CI]) between zilebesiran and placebo for the olmesartan, amlodipine, and indapamide groups were −4.0 (−7.6, −0.3), −9.7 (−12.9, −6.6), and −12.1 (−16.5, −7.6) mmHg, respectively, for 24-hr mean ambulatory SBP (all p<0.05). LSMD (95% CI) in office SBP for the same groups were −7.0 (−10.4, −3.6), −10.2 (−13.5, −6.9), and −18.5 (−22.8, −14.2) mmHg, respectively, (all p<0.001). SBP reductions were consistent across subgroups, except for a trend towards an attenuated response observed in Black patients (Figs 1, 2). More patients receiving zilebesiran (49–58%) than placebo (39–48%) experienced ≥1 adverse event through Month 6, with low rates of hyperkalaemia, hypotension, or acute kidney injury reported across all groups. Conclusion In KARDIA-2, a single dose of zilebesiran significantly reduced SBP versus placebo at Month 3 on top of a standard oral antihypertensive, with encouraging safety data. SBP reduction was consistent across most subgroups. Treatment with zilebesiran combined with standard antihypertensives may be effective for a broad population of patients with hypertension uncontrolled on monotherapy.

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.

Nighttime blood pressure reductions after radiofrequency renal denervation through 24 months in patients with uncontrolled hypertension: pooled analysis from the SPYRAL HTN trials

Abstract Introduction Studies have shown that elevated nighttime and early morning systolic blood pressure (SBP) are associated with the highest risk for cardiovascular (CV) events. Radiofrequency renal denervation (RF RDN) is an interventional therapy to reduce BP in patients with uncontrolled hypertension (HTN). Although sustained, durable reductions in office and 24-h ambulatory systolic BP (SBP) after RDN have been observed, whether the therapy produces similar, durable nighttime and early morning SBP reductions requires further evaluation. Objective To assess whether RF RDN significantly reduces nighttime SBP through long-term follow-up, in addition to other times of the day. Methods We pooled data from patients with uncontrolled HTN undergoing RF RDN using the latest-generation Symplicity SpyralTM multi-electrode catheter from the published SPYRAL HTN-OFF and -ON MED clinical trials. Office and 24-h ambulatory SBP were evaluated from baseline through 24 months. We also assessed BP changes during specific, diurnal time ranges including nighttime (1am-6am), early morning (7am-9am), and daytime (9am-9pm). The number of antihypertensive drugs and drug burden (determined by number of classes and prescribed dosage) from urine and plasma drug testing were tabulated from baseline through 24 months. Results Outcomes from 388 patients undergoing RF RDN were pooled for this analysis. Patients were on average 54±10yrs old, 26.8% female, mean BMI was 31.3±6.0, 45.1% with >10yrs diagnosis of hypertension, 7.7% with type 2 diabetes, 9.8% with obstructive sleep apnea, 47.7% with a history of smoking. The baseline nighttime SBP was 139±11mmHg, morning SBP was 154±15mmHg, and daytime SBP was 156±9mmHg. At baseline, 92.5% of patients had nocturnal hypertension (BP ≥120/70 mmHg) and took 1.0±1.2 antihypertensive drugs. 12 months after RF RDN, 30.6% of patients no longer had nocturnal hypertension (p<0.0001). The mean nighttime SBP change at 12 months was -10.8±15.4mmHg, morning changed was -12.8±20.4mmHg, and daytime changed was -12.2±13.6mmHg (Figure). The mean 24-h ambulatory SBP change at 12 months was -11.9±12.4mmHg, and the office SBP change was -17.7±15.4mmHg . Patients took 1.8±1.1 antihypertensive drugs at 12 months. Results from 24 months, not currently available, will also be presented for the first time. Conclusions In this pooled cohort of RDN patients with uncontrolled hypertension, nocturnal hypertension was highly prevalent. Clinically meaningful reductions at 12 months throughout the 24-hr circadian cycle, including at nighttime and early morning SBP, are consistent with the "always on" effect of RDN. Results from 24 months will also be presented for the first time at ESC. As an adjunctive therapy to pharmacotherapy, RDN may help to reduce CV risk by lowering nighttime and morning SBP.

Design and implementation of digital home blood pressure monitoring based on Bluetooth and WeChat App in the FAIR-Pilot study

Abstract Background Home blood pressure monitoring (HBPM) could be an alternative way to office blood pressure and ambulatory blood pressure monitoring for hypertensive patient management. However, the measurement protocol of HBPM still requires standardization, which may be improved by digital technology. Purpose To investigate the use of digital HBPM management in hypertensive patients and its application in clinical practice. Methods Fractional Flow Reserve to Determine the Appropriateness of Percutaneous Renal Artery Intervention in Atherosclerosis Renal Hypertension Patients (FAIR)-pilot study is a multicenter pilot randomized controlled trial exploring the application of fractional flow reserve (FFR) to guide the renal artery stenting in patients with renovascular hypertension. After randomization and FFR measurement, participants were divided into stenting with FFR≥ 0.8 (Stent group), no stent implantation with FFR≥ 0.8 (No stent group), and stenting with FFR＜ 0.8 (Controlled group). Participants of the FAIR-pilot study enrolled from February 1st, 2023 to February 25th, 2024 were included. A validated Bluetooth blood pressure monitor was given to every participant at the time of enrollment. Participants were taught to undertake standardized HBP and were advised to take morning and night HBPs every day. HBPM data were automatically uploaded to a WeChat App developed by FAIR investigators and could be reviewed by both participants and investigators. Twice-daily blood pressure reports were automatically generated and sent to investigators for participant compliance monitoring and reminding (Figure 1). HBPM data and blood pressure variability were analyzed. Results A total of 93 participants with 58 males (62.4%) and a mean age of 59.97 ± 16.18 years, including 26,802 HBP readings were analyzed. The average numbers of daily HBP measurement were similar between three groups and were all less than twice a day. Systolic HBP decreased from 143.11 ± 14.91 to 133.01 ± 13.01mmHg after the procedure in the Controlled group, which was more than the other two groups (140.51 ± 13.38 to 138.53 ± 17.30 mmHg and 136.20 ± 15.67 to 130.84 ± 11.04 mmHg). During the follow-up after the procedure, the HBP variability (BPV) of overall participants was 13.78 ± 4.87 and 5.46 ± 3.14 for systolic and diastolic BP, respectively. The systolic BPV of No stent group was higher than the other two groups (No stent vs. Stent vs. Controlled: 33.00 ± 9.49 vs. 8.34 ± 2.86 vs. 9.12 ± 2.71, P=0.125), however without statistical significance. Similar was found for morning and night systolic BPVs. (Table 1). Conclusion Digital HBPM management via novel information technology is feasible in the hypertension field and could be a helpful tool in clinical practice.

Time-series clustering of raw recordings of 24-hour ambulatory blood presssure for risk stratification in general population

Abstract Objective 24-hour ambulatory blood pressure measurements (ABPM) is the best out-of-office BP measurement used to refine cardiovascular (CV) risk stratification. Currently, only summary ABPM indexes are used in the clinical practice while the temporal characteristics of the raw BP recordings have not been explored. Therefore, in this study we employed an unsupervised machine learning (ML) algorithm suitable for multivariate time-series analysis to identify distinct BP and heart rate (HR) profiles associated with the incidence of adverse CV events. Design and Method In 1391 community-dwelling individuals (mean age, 46.9 years; 50.97% women), we acquired 24-hour ABPM and clinical data and collected CV events (n=399) on average 22 years later. We employed multivariate dynamic time warping and k-medoids algorithm on the raw recordings of systolic and diastolic BP and HR. To assess the clinical significance of the derived clusters, we compared the clinical characteristics and the incidence of adverse events. We validated the trained model using 24-hour ABPM obtained from external population cohort (n=1137). Results The silhouette score and Dunn index showed that the optimal number of clusters was 4. Across all clusters we observed significant difference in age and sex distribution. Cluster 4 had the worst CV risk factors profiling, with higher office BP and anti-hypertensive medication intake compared to the other clusters. We observed differences in the incidence of adverse events between clusters (Figure), with cluster 1 representing the lowest risk group and cluster 4 the highest. After adjusting for traditional CV risk factors, including office systolic BP, cluster 1 had the lowest risk (HR:0.92; 95%CI:0.84-0.99; P=0.036) and cluster 4 the highest (HR:1.13; 95%CI:1.03-1.24; P=0.006) as compared to the average population risk. The analysis of the external validation cohort revealed similar ABPM patterns and clinical characteristics. Conclusion Employing an unsupervised ML model on the raw ABPM recordings we identified clinically meaningful clusters associated with an increasing cumulative incidence of CV events. This ML analysis paves the way towards utilization of temporal BP and HR information and subsequently optimization of CV risk stratification.