Blood Pressure Lowering Therapy Research Articles

2023 Australian guideline for assessing and managing cardiovascular disease risk.

The 2023 Australian guideline for assessing and managing cardiovascular disease risk provides updated evidence-based recommendations for the clinical assessment and management of cardiovascular disease (CVD) risk for primary prevention. It includes the new Australian CVD risk calculator (Aus CVD Risk Calculator), based on an equation developed from a large New Zealand cohort study, customised and recalibrated for the Australian population. The new guideline replaces the 2012 guideline that recommended CVD risk assessment using the Framingham risk equation. The new guideline recommends CVD risk assessment in people without known CVD: all people aged 45-79 years, people with diabetes from 35 years, and First Nations people from 30 years. The new Aus CVD Risk Calculator should be used to estimate and categorise CVD risk into low (< 5% risk over five years), intermediate (5% to < 10% risk over five years) or high risk (≥ 10% over five years). The following reclassification factors may be applied to recategorise calculated risk to improve accuracy of risk prediction, particularly in individuals close to a risk threshold: Indigenous status/ethnicity, estimated glomerular filtration rate, urine albumin to creatinine ratio measurements, severe mental illness, coronary artery calcium score and family history of premature CVD. A variety of communication formats is available to communicateCVD risk to help enable shared decision making. Healthy lifestylemodification, including smoking cessation, nutrition, physical activity and limiting alcohol, is encouraged for all individuals. Blood pressure-lowering and lipid-modifying pharmacotherapies should be prescribed for high risk and considered for intermediate risk individuals, unless contraindicated or clinically inappropriate. Reassessment of CVD risk should be considered within five years for individuals at low risk and within two years for those with intermediate risk. Reassessment of CVD risk is not recommended for individuals at high risk. CHANGES IN ASSESSMENT AND MANAGEMENT AS A RESULT OF THE GUIDELINE: The updated guideline recommends assessment over a broader age range and uses the Aus CVD Risk Calculator, which replaces the previous Framingham-based equation. It incorporates new variables: social disadvantage, diabetes-specific risk markers, diagnosis of atrial fibrillation and use of blood pressure-lowering and lipid-modifying therapies. Reclassification factors are also a new addition. Updated risk categories and thresholds are based on the new AusCVD Risk Calculator. The proportion of the population in the high risk category (≥ 10% over five years) is likely to be broadly comparable to more than 15% risk from the Framingham-based equation. The full guideline and Aus CVD Risk Calculator can be accessed at www.cvdcheck.org.au.

Early blood pressure lowering therapy is associated with good functional outcome in patients with intracerebral hemorrhage

BackgroundThe implementation of a care bundle might improve functional outcome for patients with intracerebral hemorrhage (ICH). However, the impact of anti-hypertensive treatment on ICH outcomes remains uncertain. Our objective is to examine whether early blood pressure (BP) lowering therapy within first 12 h is associated with good outcome in ICH patients.MethodsWe included acute ICH patients who had baseline computed tomography (CT) scans within 6 h after onset of symptoms between October 2013 and December 2021. Early BP reduction was defined as use of anti-hypertensive agents within 12 h after onset of symptom. The clinical characteristics were compared between patients who received early BP lowering therapy and those without. The associations between early BP lowering and good outcome and functional independence at 3 months were assessed by using multivariable logistic regression analyses.ResultsA total of 377 patients were finally included in this study for outcome analysis. Of those, 212 patients received early BP reduction within 12 h after ICH. A total of 251 (66.6%) patients had good outcome. After adjustment for age, admission systolic BP, admission GCS score, baseline hematoma volume, hematoma expansion, and presence of intraventricular hemorrhage, early BP lowering therapy was associated with functional independence (adjusted odd ratio:1.72, 95% confidence interval:1.03–2.87; P = 0.039) and good outcome (adjusted odd ratio: 2.02, 95% confidence interval:1.08–3.76; P = 0.027).ConclusionsIn ICH patients presenting within 6 h after symptom onset, early BP reduction within first 12 h is associated with good outcome and functional independence when compared to those who do not undergo such early intervention. Implementation of quality measures to ensure early BP reduction is crucial for management of ICH.

Implantable cardioverter defibrillator and cardiac resynchronization treatment in people with type 2 diabetes: a comparison with age- and sex matched controls from the general population

BackgroundIncreased risk of severe tachyarrhythmias is reported in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to explore if treatment with cardiac implantable electronic device (CIED) such as implantable cardioverter defibrillator (ICD), cardiac resynchronization therapy- pacemaker and -defibrillator (CRT-P/CRT-D) differed in patients with vs. without T2DM. A secondary aim was to identify patient characteristics indicating an increased CIED treatment.Method416 162 adult patients with T2DM from the Swedish National Diabetes Registry and 2 081 087 controls from the Swedish population, matched for age, sex and living area, were included between 1/1/1998 and 31/12/2012 and followed until 31/12/2013. They were compared regarding prevalence of ventricular tachycardia (VT) at baseline and the risk of receiving a CIED during follow-up. Multivariable Cox regression analysis was performed to estimate the risk of CIED-treatment and factors identifying patients with such risk.ResultsVentricular fibrillation (VF) (0.1% vs 0.0004%) and (VT) (0.2% vs. 0.1%) were more frequent among patients with T2DM compared to controls. CIED-treatment was significantly increased in patients with T2DM both in unadjusted and adjusted analyses. HR and 95% CI, after adjustment for sex, age, marital status, income, education, country of birth, coronary artery disease and congestive heart failure, were 1.32 [1.21–1.45] for ICD, 1.74 [1.55–1.95] for CRT-P and 1.69 [1.43–1.99] for CRT-D. Blood-pressure and lipid lowering therapies were independent risk factors associated to receiving CIED, while female sex was protective.ConclusionsAlthough the proportion of VT/VF was low, patients with T2DM had a higher prevalence of these conditions and increased risk for treatment with CIED compared to controls. This underlines the importance of recognizing that T2DM patients have an increased need of CIED.

Treatment patterns in a population of 1.4 million individuals qualifying for initiation of dual-combination blood pressure lowering therapy representing usual clinical practice

Abstract Background Guidelines recommend dual-combination therapy (DCT) in most hypertensive patients requiring initiation of blood pressure (BP)-lowering treatment. This strategy is proven to be more effective as compared to monotherapy in achievement of BP goals, is associated with improved adherence, persistence and reduces risk of cardiovascular (CV) events. Purpose To describe the patterns of treatment with BP-lowering therapies in a large hypertensive population qualifying for initiation of DCT. Methods The study utilized following linked databases in England: Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics. Adults qualifying for DCT as per the 2018 ESC/ESH guidelines were identified during a 15-year period (2005-2019). The index date is the first date when patient became eligible for initiation of DCT as per the guidelines-based criteria. Patients were followed for 5 years from the index date and were categorized into 4 groups: (1) no treatment, (2) monotherapy, (3) combination therapy with 2 agents, (4) combination therapy with ≥3 agents. For each year during follow-up, the percent of patient-time (Pt) on these categories was summarized for the overall population and two main subgroups i.e., atherosclerotic cardiovascular disease (ASCVD) and diabetes at baseline. In addition, we estimated the 15-year event rate for the composite endpoint of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, and CV death via the Kaplan Meier method. Results Overall, 1,426,079 individuals met the selection criteria. Mean (SD) age was 62.9 (14.1) years and ∼50% were male. Approximately 15.9% and 13.8% had ASCVD and diabetes at baseline, respectively. In overall population during 5-year follow-up (Table 1), nearly 25% of Pt during follow-up reported non-treatment with any BP-lowering therapy. Monotherapy was most common treatment pattern accounting for nearly 50% of Pt while only 25% of Pt represented DCT. Percent of Pt on monotherapy decreased from 56.7% to 42.6% (year-1 to -5), and the percent of Pt on dual-combination therapy increased from 14.9% to 25.5% (year-1 to -5). Percent of Pt on any combination therapy (≥2 agents) increased from 17.5% to 32.4% (year-1 to -5). Similar pattern was observed in ASCVD and diabetes subgroups. The 15-year event rate for the composite endpoint was 27.1% for the overall population and was 57.5% and 40.1% in ASCVD and diabetes subgroups, respectively (Table 2). Conclusion Our findings indicate an opportunity for substantial improvement in BP control and CV risk reduction in this population, by ensuring appropriate guideline-based initiation, of dual combination BP-lowering therapy.Table 1Table 2

Individual lifetime benefit from low-dose colchicine in patients with chronic coronary artery disease.

Low-dose colchicine reduces cardiovascular risk in patients with coronary artery disease (CAD), but absolute benefits may vary between individuals. This study aimed to assess the range of individual absolute benefits from low-dose colchicine according to patient risk profile. The European Society of Cardiology (ESC) guideline-recommended SMART-REACH model was combined with the relative treatment effect of low-dose colchicine and applied to patients with CAD from the Low-Dose Colchicine 2 (LoDoCo2) trial and the Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease (UCC-SMART) study (n = 10 830). Individual treatment benefits were expressed as 10-year absolute risk reductions (ARRs) for myocardial infarction, stroke, or cardiovascular death (MACE), and MACE-free life-years gained. Predictions were also performed for MACE plus coronary revascularization (MACE+), using a new lifetime model derived in the REduction of Atherothrombosis for Continued Health (REACH) registry. Colchicine was compared with other ESC guideline-recommended intensified (Step 2) prevention strategies, i.e. LDL cholesterol (LDL-c) reduction to 1.4 mmol/L and systolic blood pressure (SBP) reduction to 130 mmHg. The generalizability to other populations was assessed in patients with CAD from REACH North America and Western Europe (n = 25 812). The median 10-year ARR from low-dose colchicine was 4.6% [interquartile range (IQR) 3.6-6.0%] for MACE and 8.6% (IQR 7.6-9.8%) for MACE+. Lifetime benefit was 2.0 (IQR 1.6-2.5) MACE-free years, and 3.4 (IQR 2.6-4.2) MACE+-free life-years gained. For LDL-c and SBP reduction, respectively, the median 10-year ARR for MACE was 3.0% (IQR 1.5-5.1%) and 1.7% (IQR 0.0-5.7%), and the lifetime benefit was 1.2 (IQR 0.6-2.1) and 0.7 (IQR 0.0-2.3) MACE-free life-years gained. Similar results were obtained for MACE+ and in American and European patients from REACH. The absolute benefits of low-dose colchicine vary between individual patients with chronic CAD. They may be expected to be of at least similar magnitude to those of intensified LDL-c and SBP reduction in a majority of patients already on conventional lipid-lowering and blood pressure-lowering therapy.

BASELINE REMNANT CHOLESTEROL MODIFIES THE EFFECT OF INTENSIVE BLOOD PRESSURE CONTROL ON CARDIOVASCULAR OUTCOMES IN PATIENTS WITH TYPE 2 DIABETES: THE ACCORD-BP TRIAL

Objective: The equivocal benefit of intensive blood pressure lowering in patients with diabetes may be partially due to the neglected residual cardiovascular risk. However, it remains uncertain whether residual cholesterol (RC) level affect the benefit of intensive blood pressure lowering in patients with diabetes. We aimed to determine whether the treatment difference of intensive versus standard blood pressure therapy on risk of cardiovascular events (CVD) in the ACCORD-BP trial depended on baseline RC level. Design and method: Participants in the ACCORD-BP trail were divided into two groups based on baseline RC levels (low RC: &lt; 31 mg/dL and high RC: 31mg/dL and higher). We report the primary outcomes identical to those used in the original ACCORD trial, which included nonfatal myocardial infarction, nonfatal stroke, and/or incident cardiovascular death. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) estimated from stratified Cox regression models were used to quantify the association between intensive therapy and incident CVD for the 2 different baseline RC groups. Results: The incident rate was significantly lower in the intensive-therapy group as compared with standard-therapy group in the low RC group (log-rank P = 0.029) but not in the high RC group (log-rank P = 0.74). Compared with standard therapy, intensive therapy was associated with a lower risk of incident CVD among participants with low RC (aHR: 0.71; 95% CI: 0.53 to 0.94), but not among participants with high RC (aHR: 1.04; 95% CI: 0.80 to 1.35). The same pattern was observed for nonfatal stroke (aHR [95% CI] in participants with low RC: 0.48 [0.25-0.93]; aHR [95% CI] in participants with high RC: 0.76 [0.41-1.41]). Subgroup analyses revealed that the protective effect of intensive therapy against CVD events among the low RC group was not influenced by sex, previous CVD at baseline, assignment to intensive glycemic control, systolic or diastolic blood pressure at baseline, and baseline low-density lipoprotein cholesterol levels. Conclusions: Intensive blood pressure lowering therapy was effective at preventing incident CVD events in the ACCORD-BP trial participants with low baseline RC level but not in those with high RC level.

Heterogeneity in Blood Pressure Response to 4 Antihypertensive Drugs

Hypertension is the leading risk factor for premature death worldwide. Multiple blood pressure-lowering therapies are available but the potential for maximizing benefit by personalized targeting of drug classes is unknown. To investigate and quantify the potential for targeting specific drugs to specific individuals to maximize blood pressure effects. A randomized, double-blind, repeated crossover trial in men and women with grade 1 hypertension at low risk for cardiovascular events at an outpatient research clinic in Sweden. Mixed-effects models were used to assess the extent to which individuals responded better to one treatment than another and to estimate the additional blood pressure lowering achievable by personalized treatment. Each participant was scheduled for treatment in random order with 4 different classes of blood pressure-lowering drugs (lisinopril [angiotensin-converting enzyme inhibitor], candesartan [angiotensin-receptor blocker], hydrochlorothiazide [thiazide], and amlodipine [calcium channel blocker]), with repeated treatments for 2 classes. Ambulatory daytime systolic blood pressure, measured at the end of each treatment period. There were 1468 completed treatment periods (median length, 56 days) recorded in 270 of the 280 randomized participants (54% men; mean age, 64 years). The blood pressure response to different treatments varied considerably between individuals (P < .001), specifically for the choices of lisinopril vs hydrochlorothiazide, lisinopril vs amlodipine, candesartan vs hydrochlorothiazide, and candesartan vs amlodipine. Large differences were excluded for the choices of lisinopril vs candesartan and hydrochlorothiazide vs amlodipine. On average, personalized treatment had the potential to provide an additional 4.4 mm Hg-lower systolic blood pressure. These data reveal substantial heterogeneity in blood pressure response to drug therapy for hypertension, findings that may have implications for personalized therapy. ClinicalTrials.gov Identifier: NCT02774460.

36. Clinical Outcome of Intensive Blood Pressure Lowering in Diabetic Patients: A Systematic Review and Meta-analysis

Background: It remains controversial in defining the optimal blood pressure (BP) targets for diabetes mellitus (DM) patients. There were various data on intensive BP lowering management in DM population, particularly in reducing cardiovascular outcomes. Objective: This study was conducted to compare the clinical outcome of intensive and standard BP lowering management in DM patients. Methods: Randomized Controlled Trials (RCTs) from Pubmed, Proquest, Google Scholar and Cochrane Library databases which compare the clinical outcome between intensive and standard BP lowering therapy were analyzed. Meta-analysis was conducted with random effects and Mantel-Haenszel method. Results: 18723 patients with DM from 11 RCTs were included. Intensive BP lowering strategy gave less number of stroke events (RR: 0.55; 95%CI: 0.36 to 0.85; p: 0.007) compared with standard BP lowering management. Between the two groups, there was no significant difference in causing all-cause death (RR: 0.94; 95%CI: 0.83 to 1.08; p: 0.39), cardiovascular death (RR: 0.85; 95%CI: 0.52 to 1.39; p: 0.53), myocardial infarction (RR: 0.96; 95%CI: 0.85 to 1.09; p: 0.54), heart failure (RR: 0.96; 95%CI: 0.75 to 1.23; p: 0.73), microalbuminuria (RR: 0.96; 95%CI: 0.65 to 1.40; p: 0.82). In the subgroup analysis, SBP reduction to lower than 120 mmHg caused lower incidence of stroke events compared with BP target of lower than 130 mmHg (RR: 0.57; 95%CI: 0.35 to 0.93; p: 0.02). Conclusion: Intensive BP lowering strategy gave a better outcome in reducing stroke events in DM patients. Targeting SBP to below 120 mmHg showed more benefit compared with below 130 mmHg.

Association Between Magnitude of Differential Blood Pressure Reduction and Secondary Stroke Prevention

The degree to which more intensive blood pressure reduction is better than less intensive for secondary stroke prevention has not been delineated. To perform a standard meta-analysis and a meta-regression of randomized clinical trials to evaluate the association of magnitude of differential blood pressure reduction and recurrent stroke in patients with stroke or transient ischemic attack (TIA). PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from January 1, 1980, to June 30, 2022. Randomized clinical trials that compared more intensive vs less intensive blood pressure lowering and recorded the outcome of recurrent stroke in patients with stroke or TIA. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was used for abstracting data and assessing data quality and validity. Risk ratio (RR) with 95% CI was used as a measure of the association of more intensive vs less intensive blood pressure lowering with primary and secondary outcomes. The univariate meta-regression analyses were conducted to evaluate a possible moderating effect of magnitude of differential systolic blood pressure (SBP) and diastolic blood pressure (DBP) reduction on the recurrent stroke and major cardiovascular events. The primary outcome was recurrent stroke and the lead secondary outcome was major cardiovascular events. Ten randomized clinical trials comprising 40 710 patients (13 752 women [34%]; mean age, 65 years) with stroke or TIA were included for analysis. The mean duration of follow-up was 2.8 years (range, 1-4 years). Pooled results showed that more intensive treatment compared with less intensive was associated with a reduced risk of recurrent stroke in patients with stroke or TIA (absolute risk, 8.4% vs 10.1%; RR, 0.83; 95% CI, 0.78-0.88). Meta-regression showed that the magnitude of differential SBP and DBP reduction was associated with a lower risk of recurrent stroke in patients with stroke or TIA in a log-linear fashion (SBP: regression slope, -0.06; 95% CI, -0.08 to -0.03; DBP: regression slope, -0.17; 95% CI, -0.26 to -0.08). Similar results were found in the association between differential blood pressure lowering and major cardiovascular events. More intensive blood pressure-lowering therapy might be associated with a reduced risk of recurrent stroke and major cardiovascular events. These results might support the use of more intensive blood pressure reduction for secondary prevention in patients with stroke or TIA.

Is a unified blood pressure threshold feasible in the current scenario?: Commentary on the article"130/80mmHg as a unifying hypertension threshold for office brachial, office central and ambulatory daytime brachial blood pressure": Commentary on the article"130/80mmHg as a unifying hypertension threshold for office brachial, office central and ambulatory daytime brachial blood pressure".

Is a unified blood pressure threshold feasible in the current scenario?: Commentary on the article"130/80mmHg as a unifying hypertension threshold for office brachial, office central and ambulatory daytime brachial blood pressure": Commentary on the article"130/80mmHg as a unifying hypertension threshold for office brachial, office central and ambulatory daytime brachial blood pressure".

S-10-2: OPTIMAL BLOOD PRESSURE TARGET TO PREVENT SEVERE HYPERTENSION IN PREGNANCY: A SYSTEMATIC REVIEW AND META-ANALYSIS

Objective: Severe hypertension in pregnancy is a hypertensive crisis that requires urgent and intensive care due to its high maternal and fetal mortality. However, there still remain some discrepancies between guidelines in a target blood pressure to prevent severe hypertension in pregnancy. This study aimed to find the optimal blood pressure (BP) levels to prevent severe hypertension in pregnant women with nonsevere hypertension. Design and method: We searched Ovid MEDLINE and the Cochrane Library to identify all randomized controlled trials, which compared effects of antihypertensive drugs and placebo/no treatment or more intensive and less intensive BP-lowering treatments on adverse maternal and fetal pregnancy outcomes among pregnant women with nonsevere hypertension. A random effects model meta-analysis was performed to estimate the pooled risk ratio (RR) and 95% confidence interval (CI) for the outcomes. Results: Forty RCTs with 6355 patients were included in this study. BP lowering treatment significantly prevented severe hypertension (RR, 0.46; 95% CI, 0.37 to 0.56), preeclampsia (RR, 0.82; 95% CI, 0.69 to 0.98), severe preeclampsia (RR, 0.38; 95% CI, 0.17 to 0.84), placental abruption (RR, 0.52; 95% CI, 0.32 to 0.86), and preterm birth (before 37 weeks; RR, 0.81; 95% CI, 0.71 to 0.93), while the risk of small for gestational age infants was increased (RR, 1.25; 95% CI, 1.02 to 1.54). An achieved systolic blood pressure (SBP) of lower than 130 mmHg reduced the risk of severe hypertension to nearly one-third compared with an achieved SBP of 140 mmHg or higher, with a significant interaction of the BP levels achieved with BP lowering therapy. There was no significant interaction between BP lowering treatment and the subtypes of hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, and chronic hypertension. Conclusions: BP lowering treatment aimed at a SBP of lower than 130 mmHg and accompanied by careful monitoring of fetal growth might be recommended to prevent severe hypertension among pregnant women with nonsevere hypertension.

PS-BPC07-7: REDUCED EFFICACY OF BLOOD PRESSURE LOWERING DRUGS IN THE PRESENCE OF DIABETES MELLITUS: RESULTS FROM THE TRIUMPH RANDOMISED CONTROLLED TRIAL.

Objective: People with diabetes mellitus (DM) have a higher prevalence of suboptimal blood pressure (BP) control compared to those without DM. Whether the presence of DM affects the ability of antihypertensive therapies to lower blood pressure (BP) is uncertain. We investigated whether DM affects the efficacy of a low dose triple combination pill or usual care among people with mild-moderate hypertension. Design and method: TRIUMPH (TRIple pill vs Usual care Management for Patients with mild-to-moderate Hypertension) was a randomized controlled open-label trial of patients requiring initiation or escalation of antihypertensive therapy. Patients were randomised to a once-daily low-dose triple combination polypill (telmisartan 20 mg/amlodipine 2.5 mg/chlorthalidone 12.5 mg) or usual care. This analysis compared BP reduction and percentage of time below target BP in people with and without DM, both in the intervention and control groups over 24-week follow-up. Predicted efficacy of prescribed therapy was calculated using the estimation methods of Law et al. Results: The trial randomized 700 patients (56 ± 11yrs, 31% DM). There was no difference in the number of drugs prescribed or predicted efficacy of therapy between people with DM and without DM. However, the observed BP reduction from baseline to week 24 was lower in those with DM compared to non-diabetics in both the triple pill (25/11 vs 31/15 mmHg, p ≦ 0.01) and usual care (17/7 vs 22/11, p ≦ 0.01) groups. People with DM achieved lower time at target BP than non-diabetics on both the triple pill (44% vs 73%, p &lt; 0.001) and usual care (27% vs 51%, p &lt; 0.001). DM was a negative predictor of change in BP (beta-coefficient -0.08, p = 0.02) and spending majority of time at target BP (OR 0.54, p = 0.006). Conclusions: Patients with DM experienced reduced efficacy of BP lowering therapies as compared to patients without DM, irrespective of the type of BP lowering therapy received. The triple pill still produced greater BP reduction compared to usual care in patients with mild-moderate hypertension even in the presence of DM.

S-29-2: MEDICAL THERAPY FOR HEART FAILURE WITH PRESERVED EJECTION FRACTION

Hypertension constitutes the major risk factor for heart failure (HF) with preserved ejection fraction (HFpEF); prevalences above 90% have been reported. HFpEF is a prevalent clinical syndrome with increased cardiovascular morbidity and mortality comparable to HFrEF. Long specific guideline-directed medical therapy (GDMT) for HFpEF was hard to establish due to lack of convincing positive outcome data from randomized controlled trials (RCTs) mainly because of major limitations of the available studies. Available evidence has however increased with recent and larger RCTs with statistical power. Besides, control of blood pressure (BP) is widely regarded as central to the prevention and clinical care in HFpEF. Thus, in current guidelines including the 2018 European Society of Cardiology (ESC) and European Society of Hypertension (ESH) Guidelines, blockade of the renin-angiotensin system (RAS) with either angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) provides the backbone of BP lowering therapy in hypertensive patients. Although superiority of RAS blockers has not been clearly shown in dedicated RCTs designed for HFpEF, except for in re-analysis with adjustment for commonly available baseline characteristics or repeat event analysis, we propose that this core drug treatment strategy is applicable for hypertensive patients with HFpEF with the addition of some modifications. The latter apply to the use of spironolactone (MRA) apart from the treatment of resistant hypertension and the use of the angiotensin receptor neprilysin inhibitor (ARNi). In addition, novel agents such as sodium-glucose co-transporter-2 inhibitors (SGLT2-i) and finerenone (non-steroidal MRA) represent promising therapies. Besides, beta-blocker therapy is widely indicated in 60–80% of HFpEF patients due to HT with rapid heart rate (&gt;80 beats/min), rapid atrial fibrillation and/or coronary heart disease. The development of an effective and practical classification of HFpEF phenotypes and GDMT through dedicated high quality RCTs are coming towards firmer conclusions.

PS-C26-7: A SINGLE-CENTER, RETROSPECTIVE STUDY OF BLOOD PRESSURE EFFECTS OF DAPAGLIFLOZIN IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Backgrounds: Sodium-glucose transporter 2(SGLT2) inhibitors are reported to have blood pressure lowering effects in addition to glucose-lowering effects. Previous studies have shown SGLT2 inhibitors, including dapagliflozin, reduce systolic blood pressure among patients with type 2 diabetes. Its mechanism is still uncertain; however, previous studies suggest plasma reduction by osmotic diuresis and natriuresis may contribute to lowering blood pressure. Dapagliflozin was recently approved as the treatment for chronic kidney disease in Japan. Blood-pressure lowering effects of SGLT2 inhibitors among patients with chronic kidney disease (CKD) are still unknown; therefore, we investigated blood-pressure effects of dapagliflozin in patients with CKD. Design and method: Patients with chronic kidney disease (estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m2, or markers of kidney damage, or both, of at least 3 months duration) were given 10 mg dapagliflozin daily for at least 4 weeks. Patients who had any changes in their antihypertensive drug prescription during this observation period were excluded. Clinical data including blood pressure measurements, eGFR, urine protein/creatinine ratio, and urinary sodium excretion before and after administration were taken and compared. Results: Contrary to previous reports, there was no significant difference in blood pressure at two months after administration. However, there was a trend of blood pressure decline at four months. Since this study is retrospective, measurement procedures were not aligned among patients, and body fluid evaluation was not considered. These inconsistent conditions may have affected the results. Also, dapagliflozin was administered to most patients in this study at the end of fall or beginning of winter, as it was approved for CKD patients in Japan in August 2021. Decreasing temperature may have limited or countervailed the blood pressure lowering effect of dapagliflozin in the first two months. Conclusions: Our findings indicate that the use of Dapagliflozin may serve as adjunct blood pressure lowering therapy in patients with CKD. Prospective study is needed to further investigate the blood pressure effects of dapagliflozin in CKD patients.

Atrial Fibrillation Detection and Management in Hypertension.

Hypertension is prevalent in >70% of atrial fibrillation patients. In turn, hypertensive patients have up to 73% greater likelihood of atrial fibrillation. Current guidelines recommend that a systematic atrial fibrillation screening may be justified in all patients aged ≥65 years with at least 1 cardiovascular disease, including hypertension. Although most blood pressure monitors include algorithms to detect atrial fibrillation with a high sensitivity of 96 [92-98]% and specificity of 94 [91-96]%, an electrocardiography confirmation is necessary to establish a diagnosis of atrial fibrillation. Early detection and diagnosis of atrial fibrillation is important to allow initiation of atrial fibrillation management. In the Early Treatment of Atrial Fibrillation for Stroke Prevention Trial (EAST-AFNET 4), hypertension was present in 88% of participants, and early rhythm control therapy lowered the risk of adverse cardiovascular outcomes in patients with early atrial fibrillation aged >75 or with CHA2DS2-VASc score ≥2 (Congestive heart failure, Hypertension, Age ≥75 (doubled), Diabetes, Stroke (doubled), Vascular disease, Age 65-74, Sex category [female]) and cardiovascular condition. Strategies for early atrial fibrillation detection should always be linked to a comprehensive atrial fibrillation work-up infrastructure organized within an integrated ABC pathway (Anticoagulation/Avoid stroke; Better symptom control; Cardiovascular and Comorbidity optimization). For secondary prophylaxis, blood pressure control should be embedded in a combined risk factor management program. In hypertensive patients where no atrial fibrillation is detected, intensive blood pressure lowering therapy for primary prophylaxis should be initiated to reduce the risk of developing atrial fibrillation and other cardiovascular complications in the future. The aim of the article is to review the current literature on atrial fibrillation detection and management in hypertensive patients.

Distribution of cardiovascular disease risk according to SCORE2 and potential need for cholesterol and blood pressure lowering therapy in apparently healthy middle-aged individuals

Abstract Background The 2021 European Society of Cardiology (ESC) prevention guidelines recommend the Systemic Coronary Risk Estimation 2 algorithm (SCORE2) to estimate the 10-year risk of cardiovascular disease (CVD) events to guide pharmacological treatment for primary prevention in apparently healthy individuals aged 40–69 years. Purpose To assess the distribution of CVD risk according to SCORE2 and the proportion of individuals who could be eligible for pharmacological treatment of blood cholesterol and blood pressure in an apparently healthy middle-aged population in Sweden. Methods We used data from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) which used population registers to randomly recruit individuals aged 50–64 years at six Swedish study sites. Information was collected from the study participants through clinical examinations, national registries, and questionnaires. We excluded individuals with previously known atherosclerotic CVD, diabetes mellitus, or chronic kidney disease with eGFR &amp;lt;60 mL/min/1.73 m2. The SCORE2 algorithm designed for countries with moderate baseline CVD risk was used to categorize study participants' 10-year CVD risk as low-moderate (&amp;lt;5% risk); high (5-&amp;lt;10% risk); and very-high (≥10% risk). The proportions of the population who could be eligible, according to the 2021 ESC prevention guidelines, for pharmacological treatment of LDL-cholesterol (LDL-C) were assessed. Treatment thresholds for LDL-C according to SCORE2 risk were ≥1.8 mmol/L (high risk) and ≥1.4 mmol/L (very-high risk). Treatment threshold for hypertension was defined as a blood pressure ≥140/90 mmHg regardless of CVD risk. Results SCAPIS included 30,082 individuals. After exclusion criteria were applied 26,877 individuals remained (median age 57.2 years; 52.8% women). The median 10-year risk of CVD according to SCORE2 was 5.0 (interquartile range 3.0, 7.0) %. In total, 47.5% were classified as low-moderate risk, 45.9% as high risk, and 6.6% as very-high risk, with men having higher risk than women (figure). Almost all of those with high and very-high risk had LDL-C levels above the treatment thresholds. As such, according to the guidelines, lipid-lowering treatment should be considered (high risk) or was generally recommended (very-high risk) in 51.7% of the total population (Figure 1). The proportion of individuals with blood pressure ≥140/90 mmHg was 21.9%. The self-reported use of lipid-lowering therapy among low-moderate, high risk, and very-high risk individuals was 3.1%, 6.9%, and 6.3%, respectively. The use of blood pressure lowering therapy was 13.1% for those with blood pressure &amp;lt;140/80 mmHg and 29.2% for those ≥140/90 mmHg. Conclusions In this population-based study of nearly 27,000 apparently healthy middle-aged individuals in Sweden, around half of the individuals could be eligible for LDL-C-lowering therapy and around one in five could be eligible for antihypertensive therapy according to the 2021 ESC prevention guidelines. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): SCAPIS funding: The Swedish Heart-Lung Foundation and Knut and Alice Wallenberg Foundation.

Individual lifetime benefit from low-dose colchicine in chronic coronary artery disease patients

Abstract Background Low-dose colchicine reduces the risk of cardiovascular events in patients with chronic coronary artery disease (CAD), but the absolute benefit may vary between patients. Individual benefit from preventive therapies can be estimated using the guideline-recommended SMART-REACH model. Purpose This study aimed to assess the range of individual absolute 10-year and lifetime benefit from low-dose colchicine according to patient risk profile. Methods The SMART-REACH model was combined with the relative treatment effect of low-dose colchicine, and applied to all participants from the LoDoCo2 trial (n=5,522), and patients with chronic CAD from the UCC-SMART cohort (n=5,308). Individual treatment benefit was expressed as (i) 10-year absolute risk reductions (ARRs) for myocardial infarction, ischemic stroke, or cardiovascular death (MACE), and (ii) life-years gained free of MACE. Predictions were also performed for MACE plus ischemia-driven coronary revascularization (MACE+), through development of a new competing risk-adjusted lifetime prediction model in data from the REACH registry (n=14,522). Low-dose colchicine was compared to alternative intensive prevention goals, i.e. low density lipoprotein-cholesterol (LDL-c) reduction to &amp;lt;1.4 mmol/L, and systolic blood pressure (SBP) reduction to &amp;lt;130 mmHg. Results Median individual 10-year ARR for MACE from low-dose colchicine therapy was 4.6% (interquartile range [IQR] 3.6–6.0%), and median gain in life expectancy free of MACE was 2.0 (IQR 1.6–2.5) years. Median 10-year ARR for MACE+ was 8.6% (IQR 7.6–9.8%), and median gain in MACE+-free life expectancy was 3.4 (IQR 2.6–4.2) years. For intensified LDL-c and SBP reduction respectively, median 10-year ARRs were 3.0% (IQR 1.5–5.1%) and 1.7% (IQR 0.0–5.7%) for MACE, and 5.2% (IQR 2.5–8.7%) and 2.9% (IQR 0.0–9.5%) for MACE+. Median life-years gained from LDL-c and SBP reduction were 1.2 (IQR 0.6–2.1) and 0.7 (IQR 0.0–2.3) years free of MACE, and 1.8 (IQR 0.8–3.3) and 0.9 (IQR 0.0–3.4) years free of MACE+. Conclusion The individual absolute benefit from low-dose colchicine varies between patients. In an era where lipid- and blood pressure-lowering therapies are already routinely used, the benefits of low-dose colchicine are expected to be of at least similar magnitude to those of intensified LDL-c and SBP reduction in patients with chronic CAD. Funding Acknowledgement Type of funding sources: None.

Diabetes: how to manage cardiovascular risk in secondary prevention patients.

Atherosclerotic cardiovascular disease (ASCVD) commonly affects people with type 2 diabetes (T2D). Historically, traditional cardiovascular (CV) risk-lowering therapies in patients with T2D and ASCVD have included antiplatelet agents, blood pressure-lowering therapies, lipid-lowering therapies and healthy lifestyle modifications. In the past decade, multiple antihyperglycaemic agents have emerged as CV risk-lowering therapies in this population as well. This article provides a narrative review on the current non-glycaemic and glycaemic treatment options for CV risk reduction in patients with T2D and ASCVD. The FDA requirement that all new antihyperglycaemic agents undergo cardiovascular outcomes trials has demonstrated increasing evidence to support the role of glucagon-like peptide 1 (GLP1) receptor agonists and sodium–glucose cotransporter 2 (SGLT2) inhibitors as first-line agents for both glycaemic control and CV risk reduction in this population.

IDENTIFICATION OF HYPERTENSIVE PATIENTS WITH INCREASED BLOOD PRESSURE VARIABILITY USING DIFFERENT MEASUREMENT METHODS BEFORE AND AFTER TREATMENT: THE REVERENT TRIAL

Objective: Blood pressure (BP) variability (BPV) can be assessed with office (OBP), home (HBP), and ambulatory BP (ABP) measurements. In this analysis, BPV indices assessed using all the three methods were compared before and 10 weeks after administering antihypertensive drug treatment. Design and method: Untreated hypertensives (or treated after washout period) with elevated BPV (systolic HBP standard deviation [SD] &gt; 7 mmHg and/or systolic daytime ABP SD &gt; 12 mmHg), were nalysedd to ramipril 10 mg or nifedipine gastrointestinal therapeutic system (GITS) 30 mg once daily, in the context of a multicenter 10-week, prospective, nalysedd, open-label, blinded-end point study. BPV was assessed using SD and coefficient of variation (CV) [weighted SD (wSD) and weighted CV (wCV) for 24h-ABP variability) of individual measurements. Results: Data from 146 participants from three research centers (Athens, Milan, Shanghai) were nalysed (mean age 53 ± 10 [SD] years, males 60%, baseline systolic OBP, HBP and 24h-ABP 143 ± 10, 138 ± 10, and 143 ± 10 mmHg, respectively). All BPV indices (except for diastolic OBP) presented significant correlations in terms of pre- vs post- treatment, with ABP indices (especially diastolic) achieving the strongest correlations (Table). Moreover, out-of-office BPV indices (especially ABP) presented fair to moderate agreement in detecting participants with high BPV (top quartile of respective distribution) pre- vs post- treatment. Conclusions: Untreated hypertensives with high out-of-office BPV retain this classification even after BP lowering therapy, which suggests that BPV is an intrinsic feature of the individuals’ BP.

NF-κB Signaling-Mediated Activation of WNK-SPAK-NKCC1 Cascade in Worsened Stroke Outcomes of Ang II-Hypertensive Mice.

Worsened stroke outcomes with hypertension comorbidity are insensitive to blood pressure-lowering therapies. In an experimental stroke model with comorbid hypertension, we investigated causal roles of ang II (angiotensin II)-mediated stimulation of the brain WNK (with no lysine [K] kinases)-SPAK (STE20/SPS1-related proline/alanine-rich kinase)-NKCC1 (Na-K-Cl cotransporter) complex in worsened outcomes. Saline- or ang II-infused C57BL/6J male mice underwent stroke induced by permanent occlusion of the distal branches of the middle cerebral artery. Mice were randomly assigned to receive either vehicle dimethyl sulfoxide/PBS (2 mL/kg body weight/day, IP), a novel SPAK inhibitor, 5-chloro-N-(5-chloro-4-((4-chlorophenyl)(cyano)methyl)-2-methylphenyl)-2-hydroxybenzamide (ZT-1a' 5 mg/kg per day, IP) or a NF-κB (nuclear factor-κB) inhibitor TAT-NBD (transactivator of transcription-NEMO-binding domain' 20 mg/kg per day, IP). Activation of brain NF-κB and WNK-SPAK-NKCC1 cascade as well as ischemic stroke outcomes were examined. Stroke triggered a 2- to 5-fold increase of WNK (isoforms 1, 2, 4), SPAK/OSR1 (oxidative stress-responsive kinase 1), and NKCC1 protein in the ang II-infused hypertensive mouse brains at 24 hours after stroke, which was associated with increased nuclear translocation of phospho-NF-κB protein in the cortical neurons (a Pearson correlation r of 0.77, P<0.005). The upregulation of WNK-SPAK-NKCC1 cascade proteins resulted from increased NF-κB recruitment on Wnk1, Wnk2, Wnk4, Spak, and Nkcc1 gene promoters and was attenuated by NF-κB inhibitor TAT-NBD. Poststroke administration of SPAK inhibitor ZT-1a significantly reduced WNK-SPAK-NKCC1 complex activation, brain lesion size, and neurological function deficits in the ang II-hypertensive mice without affecting blood pressure and cerebral blood flow. The ang II-induced stimulation of NF-κB transcriptional activity upregulates brain WNK-SPAK-NKCC1 cascade and contributes to worsened ischemic stroke outcomes, illustrating the brain WNK-SPAK-NKCC1 complex as a therapeutic target for stroke with comorbid hypertension.