Background Single-pill combinations of 3 or more low-dose blood pressure (BP)-lowering drugs hold promise for initial or early treatment of hypertension. Objectives The authors conducted a placebo-controlled trial of a new single-pill combination containing low doses of telmisartan, amlodipine, and indapamide in 2 dose options to assess efficacy and safety. Methods This international, randomized, double-blind, placebo-controlled, parallel-group trial enrolled adults with hypertension receiving 0 to 1 BP-lowering drugs. After a 2-week placebo run-in during which any BP-lowering medication was stopped, participants were eligible if home systolic BP (SBP) was 130 to 154 mm Hg. Participants were randomized in a 2:2:1 ratio to GMRx2 1/4 dose (telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg), GMRx2 1/2 dose (telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg), or placebo. The primary efficacy outcome was difference in change in home SBP from randomization to week 4, and primary safety outcome was treatment discontinuation due to an adverse event. Results From June 14, 2021 to October 18, 2023, a total of 295 participants (mean age: 51 years; 56% female) were randomized and 96% completed the trial. Baseline mean home BP was 139/86 mm Hg and clinic BP was 138/86 mm Hg after placebo run-in. The placebo-corrected least square mean differences in home SBP at Week 4 were -7.3 mm Hg (95% CI: -4.5 to -10.2) for GMRx2 1/4 dose and -8.2 mm Hg (95% CI: -5.2 to -11.3) for GMRx2 1/2 dose; reductions for clinic BP were 8.0/4.0 and 9.5/4.9 mm Hg. At Week 4, clinic BP control (<140/90 mm Hg) was 37%, 65%, and 70% for placebo, GMRx2 <1/4> dose, and GMRx2 1/2 dose, respectively (both doses P < 0.001 vs placebo). Placebo, GMRx2-triple <1/4>, and GMRx2 1/2 treatment discontinuation due to an adverse event occurred in 1 (1.6%), 0, and 6 (5.1%), respectively; out of normal range serum sodium or potassium was observed in 4 (6.3%), 12 (10.6%), and 12 (10.1%), respectively, but no participant had a serum sodium <130/>150 mmol/L or potassium <3.0/>6.0 mmol/L. Serious adverse events were reported by 2 participants in the placebo and GMRx2 1/2 groups and none in the GMRx2 1/4 group. Conclusions In a population with mild-to-moderate BP elevation, both dose versions of the novel low-dose triple single-pill combination showed good tolerability and clinically relevant BP reductions compared with placebo. (Efficacy and Safety of GRMx2 Compared to Placebo for the Treatment of Hypertension: NCT04518306)

Two recent large trials showed the potential of single pill combinations (SPCs) with ≥3 low-dose components among people with hypertension who were untreated or receiving monotherapy. In both trials, these ‘hypertension polypills’ were superior to usual care, achieving >80% BP control without increasing withdrawal due to side effects. However, there are no such products available for prescribers. To address this unmet need, George Medicines developed GMRx2 with telmisartan/amlodipine/indapamide in three strengths (mg): 10/1.25/0.625, 20/2.5/1.25; 40/5/2.5. Two pivotal trials are ongoing to support FDA submission for the treatment of hypertension, including initial treatment. These assess efficacy and safety of GMRx2 compared to: placebo, and each of the three possible dual combinations. Regulatory submissions are planned for 2024, with the aim of providing access to GMRx2 in developed and developing regions. Wider implementation of GMRx2-based treatment strategies will be guided by further research to inform access and appropriate scale up.

Background: The Ohio Cardiovascular and Diabetes Health Collaborative (Cardi-OH) unites the 7 medical schools in Ohio to improve cardiovascular (CV) and diabetes health outcomes and eliminate disparities in Ohio’s Medicaid population. The purpose of the Cardi-OH needs assessment was to identify high priority clinical topics for the dissemination of evidenced-based best practices to providers across the state. Methods: The cross-sectional survey was distributed via REDCap (research electronic data capture) to Cardi-OH members and its external contacts (i.e., people who have engaged with Cardi-OH but are not members) in 2022. Question topics were identified by Cardi-OH members based on perceived gaps in existing content. Results: A total of 88% (n=103) of 117 Cardi-OH members and 8% (n=98) of 1,204 external contacts participated. Of those, 51% (n=53) of Cardi-OH members and 47% (n=46) of external contacts provided direct clinical care. The top items for Cardi-OH members (clinical and non-clinical combined) were: 1) lifestyle prescriptions (n=50, 49%), 2) atypical diabetes (n=38, 37%), 3) COVID-19 and cardiovascular disease (CVD) (n=38, 37%), and 3) mental health and CVD (n=38, 37%). For external contacts, the top topics were: 1) lifestyle prescriptions (n=53, 54.1%), 2) mental health and CVD (n=39, 39.8%), 3) alcohol and CVD (n=27, 27.6%), and 3) CV complications (n=27, 27.6%). Regarding social determinants of health (SDOH), Cardi-OH members prioritized: 1) weight bias and stigma (n=44, 43%), 2) family-focused interventions (n=40, 39%), and 3) adverse childhood experiences (ACEs, n=37, 36%). External contacts selected: 1) family-focused interventions (n=51, 52%), 2) implicit bias (n=43, 43.9%), and 3) ACEs (n=39, 39.8%). Conclusions: Shared prioritized topics included lifestyle, SDOH, and behavioral health; these may be useful to other professional organizations as they consider dissemination priorities. Disclosure E.A.Beverly: None. A.Kinsella: None. L.J.Lammert: None. A.Nevar: None. G.Irwin: None. C.Rollins: None. M.W.Konstan: None. S.D.Bolen: None. S.Koopman gonzalez: Research Support; Bristol Myers Squibb Foundation. K.M.Dungan: Board Member; Elsevier, Consultant; Eli Lilly and Company, Dexcom, Inc., Other Relationship; UpToDate, Research Support; Dexcom, Inc., Abbott, ViaCyte, Inc., Sanofi, Speaker's Bureau; Academy for Continued Healthcare Learning, Cardiometabolic Health Congress, Medscape, Integritas. J.T.Wright: Advisory Panel; Medtronic. K.R.Baughman: None. R.Wexler: None. L.D.Dworkin: None. G.D.Solomon: None. J.F.Lamb: None. Funding Ohio Department of Medicaid’s Medicaid Technical Assistance and Policy Program

BACKGROUND AND PURPOSE: The Systolic Blood Pressure Intervention (SPRINT) randomized trial demonstrated that intensive blood pressure management resulted in slower progression of cerebral white matter hyperintensities, compared with standard therapy. We assessed longitudinal changes in brain functional connectivity to determine whether intensive treatment results in less decline in functional connectivity and how changes in brain functional connectivity relate to changes in brain structure. MATERIALS AND METHODS: Five hundred forty-eight participants completed longitudinal brain MR imaging, including resting-state fMRI, during a median follow-up of 3.84 years. Functional brain networks were identified using independent component analysis, and a mean connectivity score was calculated for each network. Longitudinal changes in mean connectivity score were compared between treatment groups using a 2-sample t test, followed by a voxelwise t test. In the full cohort, adjusted linear regression analysis was performed between changes in the mean connectivity score and changes in structural MR imaging metrics. RESULTS: Four hundred six participants had longitudinal imaging that passed quality control. The auditory-salience-language network demonstrated a significantly larger decline in the mean connectivity score in the standard treatment group relative to the intensive treatment group (P = .014), with regions of significant difference between treatment groups in the cingulate and right temporal/insular regions. There was no treatment group difference in other networks. Longitudinal changes in mean connectivity score of the default mode network but not the auditory-salience-language network demonstrated a significant correlation with longitudinal changes in white matter hyperintensities (P = .013). CONCLUSIONS: Intensive treatment was associated with preservation of functional connectivity of the auditory-salience-language network, while mean network connectivity in other networks was not significantly different between intensive and standard therapy. A longitudinal increase in the white matter hyperintensity burden is associated with a decline in mean connectivity of the default mode network.

Background: Neighborhood redlining was established by the government-sanctioned Home Owners' Loan Corporation (HOLC) in the 1930s aimed to develop neighborhood risk assessment for mortgage applications in the United States. Redlining has resulted in residential segregation and has contributed to persistent systemic racism. Objectives: We sought to investigate the association between redlining and prevalent and incidence cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Methods: We linked participants from the Chronic Renal Insufficiency Cohort (patients with mild to moderate CKD enrolled 2003-2008 and followed prospectively) with historical redlining risk groups using participant residential address at enrollment. HOLC groups neighborhoods into risk groups (A-D, with A being lowest risk and D being highest risk). We examined the association between redlining groups with prevalent and incident cardiovascular events Results: A total of 1720 participants were included: 109 (6.3%) in group A, 305 (18%) in group B, 753 (44%) in group C, and 553 (32.2%) in group D. Overall, increasing neighborhood HOLC risk was associated with increased proportion of Black and Hispanic residents, younger age, proteinuria, higher systolic BP, and high sensitivity troponin levels (all P<0.01). In multivariable models, group B (Odds Ratio [OR] 2.34 (95% CI: 1.32-4.15), P=0.003), group C (OR 2.31 (1.34-3.98), P=0.003) and group D (OR 2.10 (1.21-3.65), P=0.009) were associated with increased CVD at baseline (vs group A). Among 1118 participants without baseline CVD, group D was associated with increased risk for HF or all-cause death (adjusted HR 2.63 (1.31-5.28), P=0.006) which remained unchanged after further adjustment for BNP and high-sensitivity troponins (D vs A: HR 2.55 (1.27-5.13), P=0.008). Conclusions: Historical neighborhood redlining is associated with prevalent CVD and incident heart failure/death in a contemporary cohort of patients with CKD, enrolled more than 6 decades after the redlining practices were abolished. Future studies should focus on investigating the mechanisms of this relationship and the impact of residential segregation on cardiovascular health.

Communication of the benefits and harms of blood pressure lowering strategy is crucial for shared decision-making. To quantify the effect of intensive versus standard systolic blood pressure lowering in terms of the number of event-free days Post hoc analysis of the Systolic Blood Pressure Intervention Trial A total of 9361 adults 50 years or older without diabetes or stroke who had a systolic blood pressure of 130–180 mmHg and elevated cardiovascular risk Intensive (systolic blood pressure goal <120 mmHg) versus standard blood pressure lowering (<140 mmHg) Days free of major adverse cardiovascular events (MACE), serious adverse events (SAE), and monitored adverse events (hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, or acute kidney injury) over a median follow-up of 3.33 years The intensive treatment group gained 14.7 more MACE-free days over 4 years (difference, 14.7 [95% confidence interval: 5.1, 24.4] days) than the standard treatment group. The benefit of the intensive treatment varied by cognitive function (normal: difference, 40.7 [13.0, 68.4] days; moderate-to-severe impairment: difference, −15.0 [−56.5, 26.4] days; p-for-interaction=0.009) and self-rated health (excellent: difference, −22.7 [−51.5, 6.1] days; poor: difference, 156.1 [31.1, 281.2] days; p-for-interaction=0.001). The mean overall SAE-free days were not significantly different between the treatments (difference, −14.8 [−35.3, 5.7] days). However, the intensive treatment group had 28.5 fewer monitored adverse event–free days than the standard treatment group (difference, −28.5 [−40.3, −16.7] days), with significant variations by frailty status (non-frail: difference, 38.8 [8.4, 69.2] days; frail: difference, −15.5 [−46.6, 15.7] days) and self-rated health (excellent: difference, −12.9 [−45.5, 19.7] days; poor: difference, 180.6 [72.9, 288.4] days; p-for-interaction <0.001). Over 4 years, intensive systolic blood pressure lowering provides, on average, 14.7 more MACE-free days than standard treatment, without any difference in SAE-free days. Whether this time-based effect summary improves shared decision-making remains to be elucidated. ClinicalTrials.gov Registration: NCT01206062

Introduction: Ambient air pollution has been linked with increased cardiovascular risk, yet the mechanisms of this are incompletely understood. We sought to investigate the linkage between ambient particulate matter (PM 2.5 ) and pulse wave velocity (PWV), a marker of arterial stiffness, in the systolic blood pressure intervention trial (SPRINT). Methods: A subset of SPRINT participants underwent PWV measurements at baseline, and annually through 3 years using the Sphygmocor CPV® system and were linked with ambient PM 2.5 using participant address at study entry. Spearman’s correlations and linear regression analyses were performed to investigate the relationship between PM 2.5 , baseline PWV, and change in PWV through year 3. Results: A total of 517 participants were included (259 to standard BP, and 258 to intensive BP). Mean PM 2.5 was 9.5±1.8 μg/m 3 and mean baseline PWV was 10.7±2.7 m/s. Over 3 years, PWV increased by a mean of 0.27 m/sec from baseline (P<0.001). There was no correlation between PM 2.5 and PWV at baseline (rho=0.01, P=0.84) or year 1 (rho=0.04, P=0.38). PM 2.5 , however, significantly correlated change in PWV between baseline and year 2 (rho=0.23, P<0.001), and between baseline and year 3 [ΔPWV 0-3 ] (rho=0.26, P<0.001). The association between PM 2.5 and ΔPWV 0-3 was similar in the intensive (rho=0.29, P<0.001) and standard BP arms (rho=0.25, P<0.001). After adjusting for age, sex, race, study randomization, Framingham risk score, smoking, prevalent cardiovascular disease, and eGFR, PM 2.5 remained associated with ΔPWV 0-3 (β 0.37 per 1 μg/m 3 of PM 2.5 , standard error 0.06, P<0.001). Among participants living under the national air quality of 12 μg/m 3 , there was no change in PWV over 3 years (ΔPWV 0-3 0.13 m/s, P=0.26) while participants living above the NAAQS threshold experience significantly increased PWV over 3 years (ΔPWV 0-3 1.3 m/s, P<0.001), P=0.001 between PM 2.5 <12 vs ≥12 μg/m 3 . Conclusions: SPRINT participants who live in areas with higher ambient air pollution (PM 2.5 ) levels experienced larger increase in PWV over 3 years, without a significant impact of intensive BP lowering strategy. Arterial stiffness should be investigated as a mediator of air pollution-related cardiovascular risk.

Diets high in sodium have long been known to raise blood pressure, which, in turn, increases the risk of cardiovascular disease. Though authoritative recommendations have been made in the past several decades for federal policies and programs to reduce sodium consumption, measures adopted to date have not been effective. We recommend a comprehensive public health approach to reduce sodium in the food supply and prevent thousands of unnecessary deaths and billions of dollars in health-care costs each year.

AbstractBackgroundHypertension is a major risk factor for cardiovascular and cerebrovascular disease including stroke, small vessel disease, and dementia. The Systolic blood PRessure INTervention (SPRINT) randomized trial prospectively evaluated the effects of intensive systolic blood pressure (SBP) control (target SBP<120mmHg) versus standard control (SBP<140mmHg) on cardiovascular outcomes in individuals without baseline diabetes or stroke, and included cerebral blood flow (CBF) measurements. Previous studies with much smaller sample sizes and shorter duration suggested stable CBF in response to intensive treatment (SBP<125mmHg) [1], but long term effects are unknown. We evaluated the long‐term effects of intensive blood pressure treatment on CBF.MethodWhole brain CBF was measured at 3T using pseudocontinuous arterial spin labeled (ASL) perfusion MRI at baseline and after 3.9±0.3 years. Total white matter lesion (WML) load was measured from Fluid Attenuated Inversion Recovery T2 MRI. Data from 324 subjects with adequate ASL scan quality acquired from 6 sites were included.ResultDemographics and scanner specific CBF values are provided in Table 1. The intensive treatment group was older (p=0.01), but was otherwise similar to the standard group at baseline. There was a significant effect on the longitudinal CBF change (p=0.006) of the intensive treatment (5.7% increase) compared to the standard treatment (4.0% decrease, Fig 1). Secondary analysis showed a significant increase in age‐adjusted fractional CBF for the intensive treatment group (p<0.001) with no change (p=0.24) in the standard treatment group. Change in CBF was not associated with change in WML.ConclusionSustained intensive antihypertensive treatment does not reduce whole brain CBF, in fact it showed an increase in whole brain CBF relative to standard therapy. While improved CBF might contribute to the reduced WML progression observed in the intensive‐therapy group versus standard therapy in SPRINT[2], we did not observe a direct correlation between CBF changes and WML changes. References: (1) Croall et al. JAMA‐Neurol,2018; (2) Nasrallah et al., JAMA‐Neurol, 2019.

Blood pressure (BP) varies over time within individual patients and across different BP measurement techniques. The effect of different BP targets on the concordance between BP measurements is unknown. The goal of this analysis was to evaluate concordance in: 1) clinic BP and ambulatory BP, 2) clinic visit-to-visit variability and ambulatory BP variability and 3) initial and repeat ambulatory BP. We also sought to evaluate whether treatment assignment of intensive vs standard BP target affected these relationships. The Systolic Blood Pressure Intervention Trial (SPRINT) ambulatory blood pressure monitoring ancillary study obtained ambulatory BP readings in 897 SPRINT participants at the 27 month follow up visit and 203 consecutive repeat ambulatory BP readings taken an average of 9.8 months later. There was poor agreement between clinic systolic BP and daytime ambulatory systolic BP (limits of agreement in Bland-Altman plots of -21 to 34 mm Hg in the intensive treatment group and -26 to 32 mm Hg in the standard treatment group). There was poor agreement between clinic visit-to-visit variability (coefficient of variation) and ambulatory BP variability (coefficient of variation of a 24 hr ambulatory BP) with correlation coefficients for systolic BP <0.16. While there was a high correlation between ambulatory BP at 27 months and repeat ambulatory BP (r ~0.56), there was significant variability between repeat ambulatory BP assessments (limits of agreement of -27 to 21 mm Hg in the intensive group and -23 to 20 mm Hg in the standard group). In conclusion, irrespective of treatment target, we found low concordance in BP and BP variability between clinic BP and ambulatory BP, and additionally between repeat ambulatory BP assessments. These results reinforce the need for multiple guideline adherent BP measurements prior to clinical decision making.

Abstract African American (AAs) are disproportionately affected by hypertension. Developing effective outreach programs with community partners is a major public health priority and ideal to educate, empower, and offer support to self-manage hypertension in AAs. The purpose of this pilot is to investigate the effectiveness of a community outreach program using a technology-based intervention for hypertension self-management (COACHMAN) to improve blood pressure (BP) control. Forty AAs with hypertension will be randomly assigned to COACHMAN or enhanced usual care (EUC). COACHMAN is comprised of four components: self-monitoring of BP; web-based education; nurse counseling; and training on a medication management application. The primary outcome is change in BP from baseline to 3-months. We hypothesize that participants in COACHMAN (compared to EUC) will have better BP control. Findings from this study, if confirmed, will provide knowledge to the scarce literature available on technology-based interventions appropriate to help AAs self-manage hypertension and improve BP control.

Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines (guidelines) with recommendations to improve cardiovascular health. In 2013, the National Heart, Lung, and Blood Institute (NHLBI) Advisory