24-h SBP Research Articles

SUBCLINICAL MAGNETIC RESONANCE IMAGING MARKERS OF CEREBRAL SMALL VESSEL DISEASE IN RELATION TO AMBULATORY BLOOD PRESSURE MEASUREMENTS

Objective: 24-h and nighttime blood pressure (BP) levels are the strongest BP measurements associated with cardiovascular risk. However, it remains undocumented which of the ambulatory BP measurements have the strongest association and predictive information in relation to the presence of cerebral small vessel diseases (CSVD). Design and method: A subset of Maracaibo Aging Study with 429 participants [aged 40 years or older (women, 73.7%; mean age, 59.3y)] underwent baseline brain magnetic resonance imaging to visualize CSVD, which included log-transformed white matter hyperintensities (log-WMH), the presence (yes/no) of silent brain infarcts (SBI), cerebral microbleeds (CMB), or enlarged perivascular spaces (EPVS). Linear and logistic regression models were applied to examine the association between CSVD and each + 10 mmHg increment in the office and ambulatory systolic BP. Improvement in the fit of nested logistic models was assessed by the log-likelihood ratio and the generalized R2 statistic. Results: Office and ambulatory systolic BP measurements were related to log-WMH (beta correlation coefficients above 0.08; P < 0.001). SBI and CMB were only associated with ambulatory systolic BP measurements (odds ratios [OR] ranged from 1.31 [95% confidence interval, 1.10 1.55] to 1.46 [1.17–1.84], P < 0.003). Accounted for daytime systolic BP, both the 24-h (beta correlation, 0.170) and nighttime (beta, 0.038) systolic BP measurements remained related to log-WMH. When accounted for 24-h or daytime systolic BP levels, the nighttime systolic BP retained the significant association with SBI (ORs, 1.05–1.06; 95% CIs, > = 1.01to< = 1.13), whereas the 24-h and daytime systolic BP levels were not associated with SBI after adjustments for nighttime systolic BP (ORs, < = 0.88; 95% CI, > = 0.77to< = 1.14). On top of covariables and office systolic BP, ambulatory systolic BP measurements significantly improved model performance (R2<3.82%). Compared to 24-h and daytime SBP, nighttime systolic BP had the strongest improvement in the model performance; for WMH (1.46% vs. 1.05%) and SBI (3.06% vs. below 2.05%). Conclusions: 24-h and nighttime systolic BP were the more robust BP measurements associated with CSVD, but for log-WMH and SBI, the nighttime systolic BP level had the strongest association. Controlling ambulatory BP levels might provide additional improvement in the prevention of CSVD

MO087: Ambulatory Blood Pressure Trajectories and Blood Pressure Variability in Kidney Transplant Recipients: A Comparative Study Against Hemodialysis Patients

Abstract BACKGROUND AND AIMS Hypertension is the most prevalent cardiovascular risk factor in kidney transplant recipients (KTRs). Preliminary data suggest similar ambulatory blood pressure (ΒP) levels in KTRs and hemodialysis (HD) patients. This is the first study evaluating in comparison the full ambulatory BP profile and short-term BP variability (BPV) in KTRs versus HD patients. METHOD Two hundred four KTRs were matched (2:1 ratio) with 102 HD patients for age and gender. BP levels, BP trajectories and BPV indices over a 24-h ambulatory BP monitoring (ABPM) in KTRs were compared against both the first and second 24-h period of a standard 48-h ABPM in HD. To evaluate the effect of renal replacement treatment and time on ambulatory BP levels, two-way-ANOVA for repeated-measurements was performed. RESULTS KTRs had significantly lower SBP and pulse-pressure (PP) levels compared with HD during all periods studied (24-h SBP: KTR: 126.5 ± 12.1 mmHg; HD first 24-h: 132.0 ± 18.1 mmHg, P = 0.006; second 24-h: 134.3 ± 17.7 mmHg, P < 0.001); no significant differences were noted for DBP levels with the exception of second nighttime. Repeated-measurements-ANOVA showed a significant effect of RRT modality and time on ambulatory SBP levels during all periods studied, and a significant interaction between-them; the greatest between-group difference in BP (KTRs—HD in mmHg) was observed at the end of the second 24-h (−13.9 mmHg, 95%CI: −21.5 to −6.2, P < 0.001). Ambulatory systolic and diastolic BPV indices were significantly lower in KTRs than in HD during all periods studied (24-h SBP-ARV: KTRs: 9.6 ± 2.3 mmHg; HD first 24-h: 10.3 ± 3.0 mmHg, P = 0.032; second 24-h: 11.5 ± 3.0 mmHg, P < 0.001). No differences were noted in dipping pattern between the two groups. CONCLUSION SBP and PP levels and trajectories, and BPV were significantly lower in KTRs compared to age- and gender-matched HD patients during all periods studied. These findings suggest a more favorable ambulatory BP profile in KTRs, in contrast with previous observations.

Association of Office and Ambulatory Blood Pressure with Left Ventricular Structure and Function in Hypertensive Patients.

ObjectiveThe current study was to evaluate the association of office blood pressure (OBP) and 24h ambulatory blood pressure (ABP) with left ventricular (LV) structure and function in hypertensive patients. Whether the association was modified by sex was also evaluated.MethodsA total of 694 hypertensive patients without cardiovascular disease were retrospectively included from the inpatient clinic. Regression analysis was performed to evaluate the association of OBP and 24h ABP parameters with LV mass index (LVMi), e’ velocity and left ventricular hypertrophy (LVH) with adjustment for covariates including age, obesity, diabetes mellitus, obstructive sleep apnea, estimated glomerular filtration rate and antihypertensive drugs.ResultsThere was no difference in OBP by sex. Compared to women, men had a higher 24h (132.6 ± 11.3 vs 129.3 ± 10.0 mm Hg), daytime (136.6 ± 12.9 vs 132.8 ± 9.5 mm Hg) and nighttime (130.3 ± 9.2 vs 125.1 ± 6.6 mm Hg) SBP. The proportion of patients with non-dipping pattern and reverse dipper pattern was also higher in men. In the overall participants, 24h, daytime and nighttime SBP, non-dipping and reverse dipper pattern were associated with LVMi, e’ velocity and LVH, which were not observed in OBP. The magnitude of the association between 24h, daytime and nighttime SBP, non-dipping and reverse dipper pattern with LVMi, e’ velocity and LVH was stronger in men than in women (P-value for interaction <0.05).ConclusionTwenty-four-hour ABP appears to be better than OBP in association with LV structural and functional alterations, and this association was modified by sex.

Prediction of cardiovascular events from systolic or diastolic blood pressure.

Over time, a focus on blood pressure has transferred from diastolic pressure to systolic pressure. Formal analyses of differences in predictive value are scarce. Our goal of the study was whether office SBP adds prognostic information to office DBP and whether both 24‐h ambulatory SBP and 24‐h ambulatory DBP is specifically important. The authors examined 2097 participants from a population cohort recruited in Copenhagen, Denmark. Cause‐specific Cox regression was performed to predict 10‐year person‐specific absolute risks of fatal and non‐fatal cardiovascular (CV) events. Also, the time‐dependent area under the receiver operator curve (AUC) was utilized to evaluate discriminative ability. The calibration plots of the models (Hosmer‐May test) were calculated as well as the Brier score which combines (discrimination and calibration). Adding both 24‐h ambulatory SBP and 24‐h ambulatory diastolic blood pressure did not significantly increase AUC for CV mortality and CV events. Moreover, adding both office SBP and office DBP did not significantly improve AUC for both CV mortality and CV events. The difference in AUC (95% confidence interval; p‐value) was .26% (‐.2% to .73%; .27) for 10‐year CV mortality and .69% (‐.09% to 1.46%; .082) for 10‐year risk of CV events. The difference in AUC was .12% (‐.2% to .44%; .46) for 10‐year CV mortality and .04% (‐.35 to .42%; .85) for 10‐year risk of CV events. Moreover, for both CV mortality and CV events, office SBP did not improve prognostic information to office DBP. In addition, the Brier scores of office BP in both CV mortality and CV events were .078 and .077, respectively. Furthermore, the Brier scores were .077 and .078 in CV mortality and CV events of 24‐h ambulatory. For the average population as those participating in a population survey, the 10‐year discriminative ability for long‐term predictions of CV death and CV events is not improved by adding systolic to diastolic blood pressure. This finding is found for ambulatory as well as office blood pressure.

Effects of ambulatory blood pressure monitoring parameters on left ventricular mass index in hypertensive children.

We aimed to evaluate the effects of blood pressure (BP) values obtained by 24-h ambulatory BP monitoring (ABPM) of hypertensive children and adolescents on left ventricular mass index (LVMI). Patients diagnosed with HT with BP measurements confirmed with ABPM and evaluated with echocardiography for LVMI were included. The patients were divided into two groups according to their BMI as obese and nonobese. SDSs of ABPM parameters were compared between the groups. A total of 158 children with HT were included in the study. Ninety of these patients were obese. In obese and nonobese cases, mean SDS levels were similar in ABPM parameters, whereas LVMI was significantly higher in obese patients ( P = 0.049). There was a significant correlation between LVMI and 24-h SBP SDS, daytime SBP SDS, 24-h SBP load and daytime BP load. In obese cases, there was a statistically significant correlation between LVMI and 24-h SBP SDS, daytime SBP SDS, 24-h SBP load, daytime SBP load as well as nighttime SBP SDS and nighttime SBP load. When the whole group was evaluated, 24-h SBP SDS was the most effective parameter influencing LVMI ( P = 0.001). Similarly, the most effective ABPM parameter on LVMI in obese patients was 24-h SBP SDS ( P = 0.001). A significantly higher rate of LVMI in obese patients suggests that obesity itself is an effective factor on LVMI. In addition, systolic hypertension is more effective on cardiac functions compared with DBP measurements and systolic-DBP dipping ratios.

Effect of SGLT-2 inhibitor, empagliflozin, on blood pressure reduction in Chinese elderly hypertension patients with type 2 diabetes and its possible mechanisms

The current study evaluated the effect of SGLT-2 inhibitor, empagliflozin, on blood pressure reduction in Chinese elderly hypertension patients with type 2 diabetes and investigated its possible mechanisms. 124 patients were randomized to receive 25 mg empagliflozin QD, or placebo double blind for 12 weeks. Patients underwent 24-h ABPM. Endothelial function and arterial stiffness were also measured prior to randomization and at week 12. At week 12, adjusted mean difference versus placebo in change from baseline in mean 24-h SBP was − 8.14 mmHg (95% CI − 10.32, − 3.96, P = 0.005). At week 12, adjusted mean difference versus placebo in change from baseline in mean 24-h DBP was − 5.27 mmHg (95% CI − 8.19, − 1.35, P < 0.001). Changes in office BP were consistent with ABPM. Empagliflozin was well tolerated. Empagliflozin was associated with significant and clinically meaningful reductions in BP versus placebo in Chinese elderly patients with type 2 diabetes and hypertension. The underlying mechanisms possiblely at least in part were the improvements of endothelial function and arterial stiffness associated with empagliflozin.Registration number: ChiCTR2100054678, Registration date: December 23, 2021.

Effect of a fixed-dose combination of Telmisartan/S-amlodipine on circadian blood pressure compared with Telmisartan monotherapy: TENUVA-BP study

BackgroundThis study evaluated the circadian efficacy of a telmisartan 40 mg/S-amlodipine 2.5 mg fixed-dose combination (Telmisartan40/S-Amlodipine2.5) compared to telmisartan 80 mg (Telmisartan80) in patients with essential hypertension who did not respond to 2–4 weeks’ treatment with telmisartan 40 mg.MethodsEligible patients with essential hypertension (clinic mean sitting systolic blood pressure [MSSBP] ≥140 mmHg, or ≥ 130 mmHg in those with diabetes mellitus or chronic kidney disease) were randomly assigned to Telmisartan40/S-Amlodipine2.5 or Telmisartan80 for 8 weeks. All patients underwent ambulatory BP monitoring (ABPM) at baseline and 8 weeks later. Primary endpoints were changes in mean 24-h SBP and DBP on 24-h ABPM from baseline after 8 weeks. Secondary endpoints were changes in daytime, nighttime, and morning SBP and DBP, and clinic MSSBP and MSDBP.ResultsA total of 316 Korean patients were enrolled, 217 patients were randomized to treatment, and 192 patients completed the study. Compared to Telmisartan80, Telmisartan40/S-Amlodipine2.5 showed significantly better reductions in 24-h mean SBP and DBP after 8 weeks. Telmisartan40/S-Amlodipine2.5 also significantly reduced secondary endpoints compared to Telmisartan80. Among 15 adverse events (7 [Telmisartan40/S-Amlodipine2.5] and 8 [Telmisartan80]), there were five adverse drug reactions; 14 events were mild, and none were identified with significant between-group differences.ConclusionsTelmisartan40/S-Amlodipine2.5 was tolerable and more effective than Telmisartan80 in lowering 24-h mean ambulatory BP in patients with essential hypertension not responding adequately to Telmisartan40. Our findings support the fact that the combination of S-amlodipine with telmisartan is more appropriate than increasing the dose of telmisartan monotherapy.Trial registrationClinicalTrials.gov, NCT02231788. Registered 4 September 2014.

Relationship between the prognostic nutritional index and resistant hypertension in patients with essential hypertension

ABSTRACT Objectives Immune system activation plays a role in resistant hypertension (RHTN) pathogenesis. The clinical effect of the prognostic nutritional index (PNI) on patients with RHTN remains unclear. The aim of this study investigated the possible correlation between PNI and RHTN. Methods In this cross-sectional study, we enrolled 180 adult subjects. In patients were classified into three groups according to their office and ambulatory blood pressure measurements (ABPM): RHTN (n = 60), controlled hypertension (CHTN, n = 60), and normotension-control (NT-C, n = 60). RHTN was defined as BP ≥140/90 mm Hg while taking ≥3 antihypertensive medications or BP <140/90 mm Hg while taking ≥4 medications. The PNI was calculated from the 10 x serum albumin (g/dL) + 0.005 x total lymphocyte count (/μL) formula. Results Office and ABPM were significantly higher in patients with RHTN. Patients in the RHTN (46.1 ± 5.3) had significantly lower PNI than that in the CHTN (54.9 ± 6.7) (P = .032), and PNIs of both hypertensive groups were significantly lower than the NT-C group (P = .019, for both). The ROC curve analysis performed to assess the predictive value of PNI for RHTN and using 50.9 optimal cutoff value of PNI for RHTN gave a sensitivity of 77% and a specificity of 68.5% (AUC = 0.73, 95% CI 0.69–0.96). Multivariate analysis indicated diabetes, 24-h ABPM SBP, CRP, pill burden, and PNI (<51.6) as independent predictors of RHTN. Conclusion This study showed that the level of PNI was significantly lower in patients with RHTN compared to patients with CHTN. PNI is independently related to RHTN.

Subclinical cardiac dysfunction in pediatric kidney transplant recipients identified by speckle-tracking echocardiography

BackgroundKidney transplantation (KTx) improves prognosis in children with kidney failure; still, these patients are prone to cardiovascular damage due to multiple risk factors. Our aim was to assess myocardial structure and function in pediatric KTx by conventional and speckle-tracking echocardiography (STE) in association with established cardiovascular risk factors.MethodsForty-two KTx and 39 healthy age- and gender-matched children were evaluated. KTx recipients were further categorized according to the control of hypertension assessed by 24-h ambulatory blood pressure monitoring (ABPM). Subjects underwent pulse wave velocity (PWV) measurement, conventional echocardiography, and 2-dimensional STE. Left and right ventricular (LV, RV) global longitudinal strain (GLS), and LV circumferential strain (GCS) were measured. Glomerular filtration rate (eGFR) was calculated according to the Schwartz formula.ResultsKTx patients had increased blood pressure and arterial stiffness. LV ejection fraction (EF) was preserved along with elevated LV mass index (LVMi) while LVGLS was significantly lower, whereas LVGCS and RVGLS were increased in KTx. Uncontrolled hypertensives had lower LVGLS compared to those with controlled hypertension. Using multiple forward stepwise regression analysis, 24-h SBP and relative wall thickness (RWT) were independent determinants of LVMi, whereas antihypertensive therapy, eGFR, and HOMA-IR were independent determinants of LVGLS.ConclusionsCardiac morphology and function show distinct changes after KTx. Along with comparable ventricular volumes, LV hypertrophy and subclinical myocardial dysfunction are present. Control of hypertension and kidney graft function are major factors of LV performance. STE may be useful to reveal early myocardial dysfunction in pediatric KTx.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information.

Association between urinary sodium-to-potassium ratio and home blood pressure and ambulatory blood pressure: the Ohasama study

No studies have demonstrated the association between urinary sodium-to-potassium (Na/K) ratio and all out-of-office blood pressure (BP) [home morning and evening BP (self-measured at home), and 24-h, daytime, and night-time ambulatory BP] in the same cohort. We aimed to assess, which type of out-of-office BP is more strongly associated with urinary Na/K ratio in the general population. This cross-sectional study was conducted in the general population of Ohasama, Japan. Home and ambulatory BP levels were measured, and 24-h urine samples were obtained from 875 participants (men, 25.5%; mean age, 60.1 years). The urinary Na/K ratio in the 24-h urine samples was calculated. The median (interquartile range) urinary Na/K ratio was 4.19 (3.36-5.26). Significant positive trends of home morning, home evening, 24-h, and daytime SBP were observed across quartiles of urinary Na/K ratio (trend P ≤ 0.041; adjusted mean values between Q1 and Q4 of urinary Na/K ratio: 121.0-125.5 mmHg for home morning, 120.1-123.8 mmHg for home evening, 121.6-123.4 mmHg for 24-h, 127.5-129.5 mmHg for daytime). Urinary Na/K ratio was not significantly associated with office or night-time SBP and nocturnal BP fall (trend P ≥ 0.13). In the model with both home morning or evening SBP and daytime SBP, only home SBP was significantly associated with urinary Na/K ratio (P ≤ 0.048 for home SBP). These findings suggest that urinary Na/K ratio might be more strongly associated with home BP than with 24-h and daytime BP but was not associated with night-time BP.

Blood Pressure Load: An Effective Indicator of Systemic Circulation Status in Individuals With Acute Altitude Sickness.

Background: Acute high altitude (HA) exposure results in blood pressure (BP) variations in most subjects. Previous studies have demonstrated that higher BP is potentially correlated with acute mountain sickness (AMS). The BP load may be of clinical significance regarding systemic circulation status.Objectives: This study aimed to examine HA-induced BP changes in patients with AMS compared to those in healthy subjects. Further, we provided clinical information about the relationship between variations in 24-h ambulatory parameters (BP level, BP variability, and BP load) and AMS.Methods: Sixty-nine subjects were enrolled and all participants ascended Litang (4,100 m above sea level). They were monitored using a 24-h ambulatory blood pressure device and underwent echocardiography within 24 h of altitude exposure. The 2018 Lake Louise questionnaire was used to evaluate AMS.Results: The AMS group comprised more women than men [15 (65.2%) vs. 13 (28.3%), P < 0.001] and fewer smokers [4 (17.4%) vs. 23 (50.0%), P = 0.009]. The AMS group exhibited significant increases in 24-h BP compared to the non-AMS group (24-h SBP variation: 10.52 ± 6.48 vs. 6.03 ± 9.27 mmHg, P = 0.041; 24-h DBP variation: 8.70 ± 4.57 vs. 5.03 ± 4.98 mmHg, P = 0.004). The variation of mean 24-h cBPL (cumulative BP load) (mean 24-h cSBPL: 10.58 ± 10.99 vs. 4.02 ± 10.58, P = 0.016; 24-h mean cDBPL: 6.03 ± 5.87 vs. 2.89 ± 4.99, P = 0.034) was also obviously higher in AMS subjects than in non-AMS subjects after HA exposure. 24-h mean cSBPL variation (OR = 1.07, P = 0.024) and 24-h mean cDBPL variation (OR = 1.14, P = 0.034) were independent risk factors of AMS. Moreover, variation of 24-h mean cSBPL showed a good correlation with AMS score (R = 0.504, P < 0.001).Conclusions: Our study demonstrated that patients with AMS had higher BP and BP load changes after altitude exposure than healthy subjects. Excessive BP load variations were associated with AMS. Thus, BP load could be an effective indicator regarding systemic circulation status of AMS.

Paradoxical increase in ambulatory SBP in coarctation of aorta a compared to essential hypertension.

The relationship between office vs. ambulatory blood pressure (BP) indices are well-studied in patients with essential hypertension and based on these data, it is known that the average 24-h ambulatory BP is typically lower than office BP. However, emerging data show that office SBP underestimates arterial afterload in patients with coarctation of aorta (COA), and a minimal increase in stroke volume during low-intensity exercise results in an exaggerated rise in SBP as compared to those with essential hypertension. We hypothesized that COA patients will have higher ambulatory SBP and a higher prevalence of masked hypertension compared to patients with essential hypertension. Case-control study of 118 COA patients and 118 patients with essential hypertension matched by age, sex, BMI and office SBP. Although both groups had similar office SBP (132 ± 17 mmHg) by design, the COA group had paradoxical increases in 24-h ambulatory SBP (135 ± 14 vs. 126 ± 13; P < 0.001) and daytime ambulatory SBP (142 ± 16 vs. 130 ± 13; P < 0.001), and less nocturnal dipping (-3 ± 5 vs. -9 ± 4; P < 0.001). The COA group also had a higher prevalence of masked hypertension [36 (31%) vs 14 (12%); P < 0.001), and worse arterial function indices. These findings underscore the potential limitations of relying on office SBP for screening/monitoring of hypertension in COA and potential pitfalls in extrapolating essential hypertension guidelines recommendations to the treatment of COA. It also provides the rationale for further studies to determine if pharmacologic BP interventions guided by ambulatory BP data will improve clinical outcomes in the COA population.

Abstract 13446: Rapid Eye Movement Sleep is Associated With Ambulatory Blood Pressure in Hypertension

Introduction: Growing evidence suggests that aberrant sleep architecture is linked to heightened risk of cardiovascular disease independently of sleep apnea. Rapid Eye Movement (REM) sleep is characterized by increased sympathetic activity and blood pressure (BP) compared to non-REM sleep stages. However, whether REM sleep is associated with BP across the 24 hours has not been investigated. Hypothesis: We hypothesized that increased REM sleep would be associated with higher ambulatory BP. Methods: We recruited 137 individuals (58% men, aged 39±14 years, office systolic/diastolic BP [SBP/DBP] 125±14/77±11 mmHg) who completed overnight polysomnography followed by 24-h ambulatory BP monitoring. Sleep was scored according to standard criteria. 24-h, daytime, and nighttime averages were calculated for SBP, DBP and heart rate. REM sleep duration was computed as percentage of total sleep time and used to group participants into tertiles as follows: T1 (REM% ≤18.8), T2 (REM% 18.9-24), and T3 (REM% ≥24.1). Results: Sex ratio, body mass index, and apnea-hypopnea index were similar across REM tertiles, but age increased with increasing tertiles (p=0.029). 24-h SBP (T1 vs T2 vs T3: 121±12 vs 117±7 vs 124±12 mmHg, p=0.015) and DBP (72±7 vs 70±6 vs 76±8 mmHg, p&lt;0.001) differed across REM sleep tertiles, with significantly higher values in those in the highest tertile. Results were consistent when considering daytime SBP (T1 vs T2 vs T3: 126±12 vs 122±8 vs 132±14 mmHg, p&lt;0.001) and DBP (77±7 vs 76±6 vs 83±9 mmHg, p&lt;0.001), and nighttime DBP (65±9 vs 61±7 vs 65±8 mmHg, p=0.047). No differences were noted on nighttime SBP or any heart rate measures. A significant interaction was found between hypertension status and REM sleep in multiple regression analysis, with the observed associations being significant only among hypertensives (n=69). In those with hypertension, REM sleep duration was associated with 24-h mean BP independently of age, sex, body mass index, apnea-hypopnea index and antihypertensive medications (standardized beta 0.22, p=0.041). Conclusions: Longer REM sleep duration is independently associated with elevated ambulatory BP in individuals with hypertension. REM sleep may be a novel cardiovascular risk indicator in this population.

Abstract 10974: Durable Reductions in Circulating Angiotensinogen and Blood Pressure Six Months After Single Doses of ALN-AGT, an RNA Interference Therapeutic Targeting Hepatic Angiotensinogen Synthesis, in Hypertensive Patients

Introduction: ALN-AGT, a subcutaneous (SC) investigational RNA interference therapeutic targeting hepatic angiotensinogen (AGT) synthesis, is being evaluated as a novel treatment for hypertension in a multicenter, randomized, placebo-controlled single ascending dose study. Here we present new data on the long-term pharmacodynamic and antihypertensive effects of ALN-AGT six months after single-dose administration. Methods: As part of a Phase 1 program to assess the safety and tolerability of ALN-AGT, hypertensive patients (mean seated systolic blood pressure [SBP] of &gt;130 and ≤165 mmHg after a washout of antihypertensive medications) were randomized 2:1 to ascending single doses of ALN-AGT (10-800 mg) or placebo. Change from baseline BP was measured by ambulatory BP monitoring (ABPM) at Week 8, Week 12, and Month 6. Interim results as of May 28, 2021 are reported. Results: 84 hypertensive patients (mean age 53 years, 61% male, 26% black, mean (SD) baseline 24-h SBP 140 (9) mm Hg) were enrolled in ascending single dose cohorts of ALN-AGT up to 800 mg SC. Dose-dependent and durable reductions in serum AGT levels were observed, with single doses ≥100 mg achieving serum AGT reductions &gt;90% and 24-h SBP reductions &gt;10 mm Hg (17 mm Hg in the 800 mg cohort) through Week 12. The 24-hour ABPM profile of ALN-AGT-treated patients showed sustained reductions of daytime BP with equally marked nighttime BP reduction. Notably, new data from follow-up visits show that all patients who received a single dose of 800 mg maintained serum AGT reductions &gt;90% from Week 3 to Month 6, with a mean (SD) 24-h SBP reduction of 22 (15) mm Hg at Month 6 (5 of 8 patients without add-on antihypertensive treatment). There were no treatment-related serious adverse events or clinically significant elevations in blood creatinine or potassium. No patient required intervention for hypotension. Conclusions: Single dose administration of ALN-AGT to hypertensive patients was generally well tolerated and resulted in profound reductions in serum AGT and BP through Month 6. The durable reduction of serum AGT &gt;90% with sustained 24-hour BP reduction over a period of 6 months after single dose SC administration of ALN-AGT 800 mg supports further evaluation of both quarterly and biannual dose administration.

Abstract 11276: Safety and Tolerability of ALN-AGT, an RNA Interference Therapeutic Targeting Hepatic Angiotensinogen Synthesis, in Hypertensive Patients During Sodium Depletion or Irbesartan Coadministration

Introduction: We have recently reported that ALN-AGT, a subcutaneous (SC) investigational RNA interference therapeutic targeting hepatic angiotensinogen (AGT) synthesis, reduced BP and was generally well tolerated in a single ascending dose study of hypertensive patients. To further assess its safety profile, additional studies have been initiated to test the effects of peak ALN-AGT pharmacology during salt depletion or irbesartan add-on treatment. Methods: As part of a Phase 1 program, hypertensive patients (mean seated SBP of &gt;130 and ≤165 mm Hg after washout of antihypertensive medication) were given a single dose of ALN-AGT 800 mg SC that has been shown to reduce serum AGT by ≥95%. At Day 43 (corresponding to expected peak serum AGT reduction), these ALN-AGT-treated patients were admitted to receive interventions of a 7-day sodium restricted diet (10 mmol sodium day) or a 14-day add-on treatment regimen with the angiotensin receptor blocker irbesartan 300 mg by oral administration daily. Results: In the salt depletion cohort, 12 patients (mean age 56 years, 75% male, 25% black, mean baseline 24-h SBP 141+/- 8 mm Hg) have been dosed 2:1 with ALN-AGT or placebo SC in advance of the sodium restricted diet. In the irbesartan add-on cohort, 10 patients (mean age 55 years, 30% male, 30% black, mean baseline 24-h SBP 147 +/- 8 mm Hg) have received ALN-AGT in advance of irbesartan add-on. The study has completed patient enrollment and interventions with no patient discontinuations due to AEs. The data analysis is ongoing at the time of abstract submission. Conclusions: This ongoing study will provide insight into ALN-AGT tolerability during potential augmented pharmacology, using salt restriction to test ALN-AGT’s effects during reduced extracellular fluid volume and irbesartan coadministration to assess the effects of ALN-AGT’s liver-specific AGT silencing during angiotensin II receptor blockade. Data on tolerability, laboratory safety monitoring, serum AGT reduction, RAAS-related biomarkers, and blood pressure will be presented.

Resistant hypertension must be defined by ambulatory blood pressure and pulse pressure is best predictor of new cardiovascular events

Abstract Introduction Resistant Hypertension (RH) defined by Ambulatory blood pressure monitoring (ABPM) isn't so common. Prognostic CV by ABPM of RH is uncertain. Objective RH Population defined by ABPM, followed 5.9±5.0 years and prognostic value of ABPM for new CV events (CVe). Design and method ABPM-collected 1999–2019. Identified RH patients by ABPM. Obtained anthropometric, clinic, laboratorial data from the patient and clinical records. CVe defined by: stroke (ST) (Ischemic (STisq), haemorrhagic (SThs)), Coronary Event (CD), Other CV events (OCV) (acute heart failure (HF), peripheral arterial disease (PAD). Follow-up finished with event, last evaluation of the patient or death. Results 258 patients, follow-up – 5.9±5.0 years,158 males, mean age – 60.4±11 years. Diabetes Mellitus (DM) 45.3%, Dyslipidaemia 74.4%, Obesity 45.3%, Chronic Kidney Disease 37.2%, previous CVe (PCVe) 34.5%. Observed 68 CVe: 26 ST (21 STisq, 5 SThs), 21 CD, 21 OCV (15 HF, 6 PAD). 18 death (8 unknown, 1 infection, 2 cancer, 1 sudden death, 2 STisq, 1 CD, 3 HF). When compared those with event vs no-event (fig. 1), in T student to independent samples, those with event had larger left atrium (42.6±5.7 vs 40.2±4.7, p&amp;lt;0.05), lower creatinine clearance (mL/min/1.73m2) (63.6±34 vs 74.5±33). PCVe was significantly more prevalent on those with event (c 9.8, p&amp;lt;0.01). In a multivariate Cox analysis for the risk of CVe (adjusted to age, gender, DM, PCVe, glycemia, creatinine, number of antihypertensive), Day Pulse Pressure with cut-off 60mmHg was statically significant (HR 2.46 (95% CI 1.26–4.83), p&amp;lt;0.01). In Kaplan-Meier survival curve free of events, the best CV predictor obtained was the cut-off 60mmHg of PP (24h, Day, night PP), mostly Day PP-60mmHg (log rank 9.27, p&amp;lt;0.01) (fig. 2A). When analyzed for those who had Stroke, in the multivariate Cox analysis 24h SBP (p&amp;lt;0.05, HR 1.04 (95% CI 1.00–1.07), and night SBP (p&amp;lt;0.05, HR 1.03 (95% CI 1.00–1.06) were statically significant on top of age, gender, DM, PCVe, glycemia, creatinine, number of antihypertensive. In Kaplan-Meier survival curve free of events, the best CV predictor obtained was the cut-off 60mmHg PP, mostly Day PP 60mmHg (log rank 8.5 p&amp;lt;0.01) (fig. 2B). For those who had CD in the multivariate Cox analysis, adjusted for other variables, 24h SBP (p&amp;lt;0.05, HR 1.04 (95% CI 1.00–1.07), and night SBP (p&amp;lt;0.05 HR1.03 (95% CI 1.00–1.06) were statically significant. In Kaplan-Meier survival curve free of events, night PP 60mmHg predicted CD events (log rank 4.42 p&amp;lt;0.05) (fig. 2C). For OCV the multivariate Cox analysis, adjusted for other variables, 24h PP (p&amp;lt;0.05, HR 1.04 (95% CI 1.00–1.07) and night SBP (p&amp;lt;0.05, HR 1.03 (95% CI 1.00–1.06) were statically significant for new OCV. In Kaplan-Meier survival curve free of events, best predictor was mostly night PP 60mmHg (log rank 19, p&amp;lt;0.001) (fig. 2D). Conclusion In our sample of RH the definition by ABPM is essential. PP is the key prognosis for future CVe, special if analysed by the cut of PP-60 mmHg. Funding Acknowledgement Type of funding sources: None. Kaplan-Meier survival curves

Single pill combinations present a proven fast track in practice to reach the target blood pressure

Abstract Objective To assess the efficacy of ambulatory blood pressure (BP) lowering with perindopril/amlodipine (dual SPC arm) and perindopril/amlodipine/indapamide (triple SPC arm) in newly diagnosed and uncontrolled hypertensive patients. Design and method: 450 adults with essential hypertension were assessed in the interventional, open-label, prospective, international, multicentre PRECIOUS trial. Treatment duration was 16 weeks, divided into four treatment periods. ABPM was performed at the baseline and end of the study (prior to the visit 1 and 5), with a validated automated portable BP-measuring device (Mobil-O-Graph PWA) worn on the non-dominant arm for a 24-hour period, measuring BP in 20 minutes interval during the day and 30 minutes interval during the night. At inclusion, naïve or patients uncontrolled on previous mono or dual therapy (other than perindopril/amlodipine (P/A)) were assigned to dual SPC arm with initial dose of 4/5 mg P/A. Those uncontrolled on previous dual or triple therapy were assigned to triple SPC arm with initial dose of 4/5/1.25 mg perindopril/amlodipine/indapamide (P/A/I). If office BP control was not reached, the initial dose was up titrated in 4-week intervals to 8/5 mg, 8/10 mg P/A or 8/10/2.5 mg P/A/I in dual SPC arm and to 8/5/2.5 mg, or 8/10/2.5 mg P/A/I in triple SPC arm. Results After 16 weeks of treatment the decrease in average ambulatory BP was −16.1/−10.8 mmHg (from 142.8/92.6 mmHg to 125.1/80.8 mmHg) in dual SPC arm and −21.8/−13.5 mmHg (from 147.3/93.3 mmHg to 124.2/79.0 mmHg) in triple SPC arm. The relative reductions in ambulatory BP were −11.1%/−11.3% in dual and −14.5%/−14.2% in triple SPC arm. The absolute as well as relative ABPM reductions were higher for the awake-time BP. All ambulatory BP reductions were statistically significant in both arms (p&amp;lt;0.001). 71% of patients reached the normal 24h SBP levels and 45.6% the normal 24h DBP levels. At the end of the trial, the mean dose of perindopril was 6.4±2.0 mg and of amlodipine 6.5±2.3 mg in dual SPC arm. In triple SPC arm, the mean dose of perindopril was 6.66±1.89 mg, of amlodipine 6.51±2.30 mg, and of indapamide 2.08±0.59 mg. Treatment tolerability was good. 85% of patients experienced no adverse events; the recorded ones were clinically irrelevant. Conclusions Applying dual (perindopril/amlodipine) and triple (perindopril/amlodipine/indapamide) SPC treatment strategy resulted in a significant and fast BP reduction, measured by ABPM, in naïve and in patients uncontrolled on previous therapy. In even 71% of patients normal 24h SBP was reached. It seems that adding long acting diuretic in triple SPC enhanced drug efficacy even though the patients in the triple SPC arm had a more resistant hypertension. Funding Acknowledgement Type of funding sources: None.

Abstract P175: Discovery And Validation Of Unique Associations Of DNA Methylation Regions With 24-hour Blood Pressure Phenotypes In African Americans

DNA methylation, an epigenetic mark, may reflect the interactions between DNA, environment, and lifestyle. It has been implicated in the development and progression of hypertension, a risk factor for cardiovascular disease. We hypothesize that regions of DNA methylation in blood cells can explain 24h BP phenotypes in African Americans. We performed Reduced Representation Bisulfite Sequencing (RRBS) in a discovery cohort of 281 African Americans. Several DNA methylation regions (MRs) were significantly associated with continuously monitored 24-h, daytime, or nighttime SBP, DBP, PP, and MAP after adjustments for covariates age, sex, and body mass index (False Discovery Rate (FDR) = 0.013 - 0.050). Each of these MRs explained a substantial portion of 24h BP variance, ranging from 6.5% - 9.4%. After FDR adjustment, there were no MRs significantly associated with clinic BPs (FDR &gt; 0.1374), calculated by the average of 4 resting measurements (2 per arm) by sphygmomanometer. To interrogate specific regions of DNA methylation, our lab developed a potentially clinically applicable, deep, and targeted methylation sequencing method called Bisulfite-Specific PCR ULtrapLEx Targeted Sequencing (BULLET-Seq), and tested it in two reference samples for three MRs of interest. BULLET-Seq is able to accurately quantify the 10% changes in the dilution series when methylation rates ranged from ~40% to 90% (a chr19 methylation region; R 2 = 0.95 - 0.97) and can modestly measure these changes when rates range from ~2% to 4% (a chr5 region, R 2 = 0.82), and is questionable when methylation rates are below 2% (a chr13 region, R 2 = 0.03 - 0.27). Validation of the chr19 MR in an independent cohort (n=117) was performed in a single BULLET-Seq run. After covariate adjustment, the chr19 region was significantly associated with 24h BPs (SBP, DBP, and MAP; FDR &lt; 0.05), confirming the findings from the discovery cohort. The MR accounted for up to 1.75% of BP variance in the 24h phenotypes. In conclusion, the reported DNA MRs have potential to be excellent markers for the cumulative effect of factors that influence 24h BPs and the BULLET-Seq workflow can be applied in clinical and population settings to screen up to thousands of patients.

Fatty liver index and hypertension-mediated organ damage in never-treated hypertensive patients without diabetes mellitus.

We investigated whether fatty liver index (FLI), a surrogate marker of nonalcoholic fatty liver disease (NAFLD), is associated with hypertension-mediated organ damage (HMOD) in never-treated hypertensive patients without diabetes mellitus. We performed both clinic and ambulatory blood pressure (BP) measurements, and calculated the FLI for all participants. A FLI of no less than 60 indicates a high-risk of underlying NAFLD, whereas a FLI of less than 60 indicates lower risk. We evaluated left ventricular mass (LVM) by echocardiography, arterial stiffness by carotid--femoral pulse wave velocity (PWV), capillary rarefaction by nailfold capillaroscopy, as well as urinary albumin-to-creatinine ratio (ACR). HMOD was defined according to the categorical thresholds for each domain, except for capillary rarefaction in which case the categorization of patients was made by the median. We included 146 hypertensive patients (men, 43.8%; mean age, 56.6 ± 10.8 years; BMI, 30.3 ± 4.9 kg/m2; FLI, 57.2 ± 27.7; office, systolic/diastolic, and 24-h BP, 153.5 ± 15.8/94.7 ± 9.8 mmHg, and 140.5 ± 9.9/83.8 ± 9 mmHg, respectively). Patients with FLI at least 60 (n = 76) were younger, with higher BMI and 24-h SBP, compared with patients with FLI less than 60 (n = 70). FLI was associated with HMOD after adjustment (LVM indexed to height, P = 0.004; PWV, P = 0.047; reduced capillary density, P = 0.001; and logACR, P = 0.003). High-risk FLI phenotype and FLI z scores increased the likelihood of any HMOD by 3.8 (95% confidence interval, 1.6-7.1) and 5.4 (95% confidence interval, 2.3-15.0) times, respectively. However, the increased number of HMOD domains has progressively stopped being determined by the FLI z scores (P = 0.65). High-risk FLI pattern was associated with various HMOD, and may re-classify never-treated hypertensive patients without diabetes mellitus into a higher cardiovascular risk level.

The association of dynamic thiol-disulphide balance with white-coat hypertension.

Dynamic thiol-disulphide homeostasis is an indicator of the antioxidant system that interacts early with the oxidative environment. This study aimed to assess the dynamic thiol/disulphide balance in individuals with white-coat hypertension (WCH). This cross-sectional study included a total of 117 individuals who presented to our outpatient cardiology clinic. Seventy patients were diagnosed with WCH. All blood samples were obtained from the patients after a minimum of 8 h of fasting, centrifuged immediately, stored in Eppendorf tubes, and protected at -80°C. The two groups were well-balanced in terms of age, gender, and BMI. Native thiol and total thiol levels were lower in the WCH group than in normotensive individuals. However, disulphide levels were higher in the former. Serum disulphide concentration positively correlated with 24-h SBP, and 24-h DBP. In backward stepwise logistic regression analysis, serum disulphide [odds ratio (OR) = 1.165 (1.089-1.245), 95% confidence interval (CI), P < 0.001] and serum total thiol levels [OR = 0.992 (0.984-1.000), 95% CI, P = 0.050] were independently associated with WCH. We demonstrated that dynamic thiol/disulphide balance shifted strongly towards disulphide formation due to thiol oxidation in patients with WCH.