Blood Pressure Treatment Goals Research Articles

Combined lack of blood pressure and lipid control is a major risk factor for mortality in hypertensive patients: a single-center study

Abstract Background Hypertension and dyslipidemia are well-known risk factors for cardiovascular disease (CVD). In such patients, lowering blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) and targeting to values below pre-specified cut-offs prevents CV events and improves prognosis. However, the impact of both BP and LDL-C control as compared to control of only one and/or none of these two risk factors is not well-studied. Methods Among 2,380 treated patients with hypertension and no overt CVD at baseline, we assessed the trajectory of BP control in 1,142 subjects with 4 or more follow up visits; BP control was defined as BP<140/90 mmHg in half or more visits. In the same subgroup, data on lipid control according to LDL-C goals were available in 1,032 patients in 2 or 3 visits. The HeartScore was used to estimate the risk of all-cause death at baseline. Results Across a median follow up of 108 months, 26 deaths (2.44%) were recorded. Despite appropriate anti-hypertensive treatment, 376 patients (32.92%) did not achieve conventional BP control in half or more of follow-up visits. Respectively, 59.83% of the study population did not meet the LDL-C goals in at least one assessment. Patients with suboptimal BP control had almost 3-fold increased risk for all-cause mortality (HR=2.85, 95% CI 1.31–6.21, P=0.008) as compared to subjects with effective control. This association was not attenuated after taking into account age, gender, body mass index, smoking, and diabetes mellitus (adjusted HR=2.54, 95% CI 1.13–5.72, P=0.025). Ineffective LDL-C control was not related to death (HR=1.31, 95% CI 0.688–2.48). However, patients who did not reach treatment goals for both BP and LDL showed substantially increased risk for all-cause mortality (HR=5.42, 95% CI 1.09–26.9, P=0.039). Importantly, suboptimal BP control in our cohort of hypertensive patients was associated with death independently of the HeartScore (adjusted HR=2.65, 95% CI 1.22–5.77, P=0.014) and conferred incremental reclassification value on top of the baseline risk (continuous NRI=0.467, P=0.016). Conclusions Suboptimal BP control was related to all-cause mortality in our cohort of hypertensive patients; importantly, this association was substantially stronger in concurrent presence of LDL-C values above treatment targets, thus, highlighting the need for combined achievement of BP and LDL-C control. Moreover, association of suboptimal BP controlwith death was independent of the HeartScore, suggesting that BP control should be considered in risk stratification of hypertensive patients Funding Acknowledgement Type of funding source: None

Effects of Intensive Blood Pressure Treatment on Orthostatic Hypotension

Although intensive blood pressure (BP)-lowering treatment reduces risk for cardiovascular disease, there are concerns that it might cause orthostatic hypotension (OH). To examine the effects of intensive BP-lowering treatment on OH in hypertensive adults. MEDLINE, EMBASE, and Cochrane CENTRAL from inception through 7 October 2019, without language restrictions. Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) that involved more than 500 adults with hypertension or elevated BP and that were 6 months or longer in duration. Trial comparisons were groups assigned to either less intensive BP goals or placebo, and the outcome was measured OH, defined as a decrease of 20 mm Hg or more in systolic BP or 10 mm Hg or more in diastolic BP after changing position from seated to standing. 2 investigators independently abstracted articles and rated risk of bias. 5 trials examined BP treatment goals, and 4 examined active agents versus placebo. Trials examining BP treatment goals included 18466 participants with 127882 follow-up visits. Trials were open-label, with minimal heterogeneity of effects across trials. Intensive BP treatment lowered risk for OH (odds ratio, 0.93 [95% CI, 0.86 to 0.99]). Effects did not differ by prerandomization OH (P for interaction = 0.80). In sensitivity analyses that included 4 additional placebo-controlled trials, overall and subgroup findings were unchanged. Assessments of OH were done while participants were seated (not supine) and did not include the first minute after standing. Data on falls and syncope were not available. Intensive BP-lowering treatment decreases risk for OH. Orthostatic hypotension, before or in the setting of more intensive BP treatment, should not be viewed as a reason to avoid or de-escalate treatment for hypertension. National Heart, Lung, and Blood Institute, National Institutes of Health. (PROSPERO: CRD42020153753).

Hypertension (Blood Pressure) and Lifetime Risk of Target Organ Damage.

The purpose of this review is to describe the long-term or lifetime relationship between blood pressure and target organ damage. The use of the term "blood pressure" as opposed to hypertension is purposeful. The risk of cardiovascular disease from blood pressure begins below the levels of blood pressure defined as hypertension by contemporary definitions. An important recent publication that bears on this topic was the 2017 ACC/AHA Blood Pressure Management Guidelines. The redefinition of hypertension and blood pressure treatment goal to 130/80mmHg and the decision to rely almost exclusively on data from event-based randomized controlled clinical trials, which led to a recommendation for lifestyle therapy only for most with stage 1 hypertension, were important. A report from the CARDIA study demonstrated significant risk for cardiovascular disease at 20years for stage 1 hypertension. Based on all evidence, clinicians should consider the use of medication for stage 1 hypertension in those uncontrolled on lifestyle therapy.

Blood pressure goal attainment in multi-ethnic Asian patients with hypertension and dyslipidaemia in primary care.

Hypertension and dyslipidaemia are major risk factors for cardiovascular diseases and achieving treatment goals mitigates such risks. This study determined demographic and medication-related factors associated with blood pressure (BP) goal attainment in patients with concomitant hypertension and dyslipidaemia. This paper is a sub-analysis of the Lipid HEALTH study, a questionnaire survey focusing on adult Asian patients with both dyslipidaemia and hypertension. An interviewer-administered questionnaire was used to obtain demographic and clinical information. Laboratory and prescription data was retrieved from electronic health records. BP goals were defined by international guidelines. Data was audited and analysed, and logistic regression analysis was used to identify factors determining BP goal attainment. Among the 851 included patients, 49.7% attained their BP goals. 37.0% were on monotherapy, 57.6% on ≥ 2 BP-lowering medications, and 5.4% had no pharmacologic treatment. Among those on pharmacotherapy, 51.2% failed to achieve BP goals. Calcium channel blockers were the most frequently prescribed medications. Attainment of BP goals was significantly associated with: not having Type 2 diabetes mellitus (odds ratio [OR] 2.27, 95% confidence interval [CI] 1.61-3.13); attaining low-density lipoprotein cholesterol goal (OR 2.02, 95% CI 1.45-2.81); being solely on dietary control (OR 2.19, 95% CI 1.09-4.39); and receiving monotherapy (OR 1.71, 95% CI 1.18-2.48). BP treatment goals were attained by half of the patients with dyslipidaemia and hypertension, and half of those on pharmacotherapy. Type 2 diabetes mellitus and low-density lipoprotein cholesterol control were significantly associated with BP goal attainment.

Abstract MP36: Effects Of Intensive Blood Pressure Treatment On Orthostatic Hypotension: An Individual-level Meta-analysis

Background: Intensive blood pressure (BP) treatment reduces the risk of cardiovascular disease, but there are ongoing concerns that it also might be harmful by increasing the risk of orthostatic hypotension (OH). However, individual trials have been inconclusive. Methods: In this individual participant data meta-analysis, we systematically reviewed MEDLINE, EMBASE, and CENTRAL databases through October 7, 2019 for randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) on measured OH. OH was defined as a drop in SBP ≥20 mmHg or DBP ≥10 mmHg after changing positions from seated to standing. Ultimately, five trials of BP treatment goal were identified. Effects were examined overall and in subgroups of baseline characteristics, including diabetes, standing BP pre-randomization (<110 vs ≥110 mm Hg), and pre-randomization OH. Results: There were 18,466 participants with 127,998 follow-up visits. Most trials demonstrated low risk of bias with minimal heterogeneity of effects across trials ( I 2 = 0.0%). Intensive BP treatment significantly lowered risk of OH (OR 0.93; 95% CI: 0.86, 0.99). Effects were strongest among adults without diabetes (OR 0.90 vs 1.10; P -interaction = 0.015) and adults with lower standing SBP (OR 0.66 for <110 mmHg vs 0.96 for ≥110 mmHg; P -interaction = 0.02). Effects did not differ by pre-randomization OH ( P -interaction = 0.80). In sensitivity analyses that included 4 additional placebo-controlled trials, overall and subgroup findings were unchanged ( Figure ). Conclusion: OH prior to or in the setting of more intensive BP treatment should not be viewed as a reason to avoid or to de-escalate treatment for hypertension.

P798Automated blood pressure measurements: optimal diastolic blood pressure range in treated hypertensives at high cardiovascular risk

Abstract Background/Introduction Automated office blood pressure measurements (AOBPM) is recommended for the diagnosis of arterial hypertension. Nevertheless, use of automated office blood pressure in monitoring of treated patients with hypertension is limited by the discrepancies between AOBPM, auscultatory and research grade measurements of blood pressure. The treatment targets using AOBPM are not well-determined. Purpose This post-hoc analysis is aimed to establish the optimal range for on-treatment diastolic blood pressure (DBP) measured with AOBPM in hypertensive patients without cardiovascular disease but at high risk, who achieved systolic blood pressure treatment goal (SBP). Methods Data of 3715 subjects without prior cardiovascular disease treated to achieve SBP goal <120 mm Hg were selected from SPRINT trial database obtained from National Heart, Lung and Blood Institute. Clinical endpoint was defined as myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure or death from cardiovascular causes. On-treatment blood pressure was computed as mean of AOBPM readings in a period from 6th month until to end of the study, which was considered as with a stable blood pressure. Optimal on-treatment DBP range was established on the basis of hazard ratio plot for clinical endpoint after adjustment for age, sex, SBP, smoking habits and history of chronic kidney disease. The target DBP range was set to be 10 mm Hg wide, what is line with current ESC/ESH guidelines. To evaluate nonlinear relationship between continuous variables and outcome cubic spline methods were used. Results Data of 3715 (38.3% female and 61.7% male) subjects aged 67.3±9.2 mm Hg were analysed. Mean on-treatment SBP and DBP were 120.8±8.5 mm Hg and 68.2±8.1 mm Hg, respectively. Lowest hazard risk of primary endpoint was found in on-treatment DBP range 62.8–72.8 mm Hg with a minimum at 67.8 mm Hg (Figure 1). Hazard risk increased linearly toward lower and higher values than selected optimal DBP range. Figure 1 Conclusion(s) In treated hypertensives at high cardiovascular risk, but without prior cardiovascular disease who achieved SBP treatment goal, on treatment DBP 62.8–72.8 mm Hg range should be considered when treatment is monitored using AOBPM.

P5729Restricted mean survival time analysis to assess efficacy and safety of intensive vs standard blood pressure treatment goals as a function of age: insights from the SPRINT trial

Abstract Background Blood pressure (BP) treatment targets in older adults (≥75 years) remain controversial. Restricted mean survival time (RMST) analysis is an alternative to hazard ratios (decreased reliance on proportional hazards assumption) with an intuitive interpretation of a gain or loss in event-free days. This may be valuable when assessing effectiveness and safety of BP treatment as a function of age. Purpose Determine differences in event-free time (days) between intensive (≤120 mm Hg) and conservative (≤140 mm Hg) BP treatment stratified by age categories. Methods Post hoc analysis to estimate RMST using publicly available SPRINT trial dataset for the primary SPRINT composite cardiovascular outcome and a 6-point secondary safety outcome (hypotension, syncope, bradycardia, electrolyte abnormality, injurious falls, or acute kidney injury) that resulted in emergency department visits or serious adverse events. Results In 9,361 participants the average age was 67.9±9.4 years (≤64 years: n=4,216; 65–74 years: n=2794, ≥75 years: n=2351). Over 5 years, participants in the intensive arm had an extra 13.8 cardiovascular event-free days [(3.9 to 23.6), p=0.006]; this increased to 28.6 days [(3.6 to 53.7), p=0.025] in those ≥75 years. For the 6-point composite safety outcome, participants in the intensive arm had on average significantly fewer safety event-free days compared to the control arm [−37.6 days (−54.2 to −21.1)], p<0.0001; this decreased to −8.6 days [(−43.2 to 26.1), p=0.63] in those ≥75 years. Restricted Mean Survival Time Age Category RMST (Intensive) RMST (Control) RMST (Intensive-Control Difference) P-value (Days, 95% CI) (Days, 95% CI) (Days, 95% CI) Primary SPRINT MACE Outcome All Ages 1441.9 (1435.3 to 1448.5) 1428.1 (1420.9 to 1435.3) 13.8 (3.9 to 23.6) 0.006 <65 years 1411.9 (1404.9 to 1419.0) 1401.8 (1393.4 to 1410.1) 10.2 (−0.7 to 21.1) 0.07 65–74 years 1375.2 (1363.9 to 1386.5) 1369.5 (1358.1 to 1380.9) 5.7 (−10.4 to 21.8) 0.49 ≥75 years 1393.7 (1376.9 to 1410.5) 1365.1 (1346.5 to 1383.7) 28.6 (3.6 to 53.7) 0.025 Primary Composite Safety Outcome All Ages 1370.9 (1358.7 to 1383.3) 1408.6 (1397.5 to 1419.7) −37.6 (−54.2 to−21.1) <0.0001 <65 years 1396.9 (1380.7 to 1413.1) 1439.2 (1425.6 to 1452.8) −42.2 (−63.4 to −21.1) <0.0001 65–74 years 1299.7 (1279.7 to 1319.7) 1347.5 (1330.5 to 1364.5) −47.8 (−74.0 to −21.5) <0.0001 ≥75 years 1187.6 (1162.8 to 1212.4) 1196.2 (1171.9 to 1220.4) −8.6 (−43.2 to 26.1) 0.63 RMST = restricted mean survival time; MAC = major adverse cardiovascular events. Conclusions Compared to controls, intensively treated older adults ≥75 years had larger gains in the primary cardiovascular outcome with similar losses in the composite safety outcome. Acknowledgement/Funding None

Abstract 103: The Effects of s Lower Blood Pressure Treatment Goal on Orthostatic Hypotension in Adults With Recent Stroke

Background: Lower systolic blood pressure (SBP) treatment goals reduce risk of orthostatic hypotension (OH). Whether a lower goal also reduces orthostatic symptoms is unknown. Methods: We examined the effect of SBP goal on OH in SPS3-BP (Secondary Prevention of Small Subcortical Strokes - Blood Pressure), an open label, randomized trial. Adults with a recent stroke (<6 months) were assigned to either a SBP goal of 130-149 mm Hg or <130 mm Hg. During follow-up, BP was measured 3 times in a seated position and once after 2 minutes of standing. OH was defined as a drop in SBP ≥20 mm Hg or DBP ≥10 mm Hg. We also examined extreme standing BP values (SBP ≥190 mm Hg or ≤90 mm Hg; DBP ≥110 mm Hg or ≤40 mm Hg). Participants were asked about dizziness and lightheadedness in the process of standing up. We used generalized estimating equations to account for repeat measurements. Results: During 36,342 visits, involving 2,876 participants (mean age 62.8 ± 10.7 yrs, 37% women, 16% black) with a mean of 15 follow-up visits, OH was present 2,591 times in 1,165 participants. Similarly, dizziness was present 1,343 times (in 592 participants) and lightheadedness was present 941 times (in 893 participants). A lower SBP goal (compared to standard) was associated with a lower risk of OH (OR 0.86; 95% CI: 0.75, 0.99), a higher risk of SBP ≤90 mm Hg (3.79; 2.35, 6.11) or DBP ≤40 mm Hg (2.42; 1.41, 4.15), and a lower risk of SBP ≥190 mm Hg (0.40; 0.27, 0.60) or DBP ≥110 mm Hg (0.31; 0.19, 0.50) ( Table ). BP goal did not affect dizziness or lightheadedness. Conclusions: A lower SBP goal decreased OH without affecting orthostatic symptoms. These findings support recent observations that more intensive SBP treatment does not increase risk of falls.

Abstract P2054: Experiencing the Primary Composite Cardiovascular Outcome is More Strongly Associated With Serious Adverse Events Than Intensive Treatment in the Systolic Blood Pressure Intervention Trial

Background: SPRINT was the first large-scale trial to investigate the benefits of intensive versus standard blood pressure treatment (goal of <120 vs <140 mmHg, respectively). Participants who were treated intensively experienced fewer cardiovascular events. About 38% (3529/9361) of participants had a serious adverse event (SAE), leading to debate about the role of intensive treatment in causing of SAEs. However, no study has examined cardiovascular events as an independent predictor of SAEs, accounting for other variables. Methods: SAEs were predicted using multivariable cox models. The variables were CVD composite (the original SPRINT primary outcome, included in this analyses to capture the effect of having a study event), treatment (intensive or standard), albumin (normal, micro, macro), BMI (<30 vs ≥30), estimated glomerular filtration rate (eGFR, <60 vs ≥60), statin, and aspirin use. Analyses were stratified by tertiles of baseline 10-year ASCVD risk score in those without and with baseline CVD. Thirty-eight participants were excluded due to incomplete data resulting in a sample of 9323 (mean age 68 years, 35% female). Results: In all groups, including the in-study CVD composite primary endpoint improved the harrell’s C-index of model fit. In the multivariable models, CVD composite was a predictor of SAEs in ASCVD tertiles (T1, T2, T3) and the clinical CVD group (Hazard Ratio [HR] 5.01 CI 3.86-6.51; HR 5.10 CI 4.23-6.28; HR 4.40 CI 3.79-5.10; and HR 3.67 CI 3.18-4.23, respectively). Kidney function as measured by eGFR <60 predicted SAEs in T1, T2, T3 and clinical CVD groups (HR 1.52 CI 1.26-1.84; HR 1.25 CI 1.06-1.47; HR 1.24 CI 1.10-1.40; and HR 1.20 CI 1.03-1.38, respectively). BMI ≥ 30 emerged as a predictor in T1, T2, and T3 but not in the clinical CVD group. Albuminuria, statin and aspirin use were not consistent predictors across groups. Intensive treatment predicted SAEs in T2 (HR 1.20 CI 1.04-1.38), but not in the T1, T3 and clinical CVD groups. No interaction was detected between ASCVD tertile and randomized treatment group assignment. Conclusions: These analyses demonstrated that experiencing the primary composite CVD endpoint was the strongest predictor of SAEs in all groups and that intensive treatment was a modest, infrequent predictor of SAEs.

Association of Orthostatic Hypotension Timing With Clinical Events in Adults With Diabetes and Hypertension: Results From the ACCORD Trial.

To determine the effects of orthostatic hypotension (OH) measurement timing on its associations with dizziness, falls, fractures, cardiovascular disease (CVD), and mortality. We analyzed OH measurements from the Action to Control Cardiovascular Risk in Diabetes BP trial, which evaluated two blood pressure (BP) goals (systolic BP [SBP] < 120 mm Hg vs. SBP < 140 mm Hg) and incident CVD among adults with diabetes and hypertension. Seated BP was measured after 5 minutes of rest at baseline and follow-up visits (12 months, 48 months, and exit). Standing BP was measured 3 consecutive times (M1-M3) after standing, starting at 1 minute with each measurement separated by 1 minute. Consensus OH was defined as a drop in SBP ≥ 20 mm Hg or diastolic BP (DBP) ≥ 10 mm Hg. Participants were asked about orthostatic dizziness, recent falls, and recent fractures, and underwent surveillance for CVD events and all-cause mortality. There were 4,268 participants with OH assessments over 8,450 visits (mean age 62.6 years [SD = 6.6]; 46.6% female; 22.3% black). Although all measures of consensus OH were significantly associated with dizziness, none were associated with falls, and only M2 (~3 minutes) was significantly associated with fractures. No measurements were associated with CVD events, but later measurements were significantly associated with mortality. BP treatment goal did not increase risk of OH regardless of timing. Associations were not consistently improved by the mean or minimum of M1-M3. In this population of adults with hypertension and diabetes, neither single time nor set of measurements were clearly superior with regard to outcomes. These findings support the use of a flexibly timed, single measurement to assess OH in clinical practice. Trial Number NCT00000620.

APOE genotype, hypertension severity and outcomes after intracerebral haemorrhage.

Intracerebral haemorrhage in the elderly is a severe manifestation of common forms of cerebral small vessel disease. Nearly 60% of intracerebral haemorrhage survivors will develop clinical manifestations of small vessel disease progression including recurrent haemorrhage, ischaemic stroke, dementia, late-life depression and gait impairment within 5 years. Blood pressure measurements following intracerebral haemorrhage are strongly associated with this risk. However, aggressive blood pressure lowering in the elderly carries substantial risks. In order to determine whether there might be an opportunity to select individuals at the highest risk for small vessel disease progression for aggressive blood pressure reduction, we investigated whether APOE gene variants ɛ2/ɛ4 modify the association between blood pressure and small vessel disease clinical progression after intracerebral haemorrhage. We conducted a single-centre longitudinal study at a tertiary care referral centre (Massachusetts General Hospital in Boston, MA, USA), analysing 716 consecutive survivors of acute intracerebral haemorrhage, enrolled from January 2006 to December 2016. We conducted research interviews at the time of enrolment and obtained APOE genotypes from peripheral venous blood samples. We followed patients longitudinally by means of validated phone-based research encounters, aimed at gathering measurements of systolic and diastolic blood pressure, as well as information on small vessel disease clinical outcomes (including recurrent haemorrhage, incident ischaemic stroke, incident dementia, incident depression and incident gait impairment). APOE ε4 and systolic blood pressure were associated with the risk of recurrent haemorrhage, ischaemic stroke and post-haemorrhage dementia, depression and gait impairment (all P < 0.05). APOE ε4 and systolic blood pressure interacted to increase the risk of recurrent haemorrhage, ischaemic stroke, dementia and gait impairment (all interaction P < 0.05). Among patients with elevated blood pressure following intracerebral haemorrhage (average systolic blood pressure 120–129 mmHg and diastolic blood pressure <80 mmHg) only those with one or more APOE ε4 copies were at increased risk for one or more small vessel disease outcomes (hazard ratio = 1.97, 95% confidence interval 1.17–3.31). Among haemorrhage survivors with hypertension (stage 1 and beyond) APOE genotype also stratified risk for all small vessel disease outcomes. In conclusion, APOE genotype modifies the already strong association of hypertension with multiple small vessel disease clinical outcomes among intracerebral haemorrhage survivors. These data raise the possibility that genetic screening could inform blood pressure treatment goals in this patient population.

Long-term, telephone-based follow-up after stroke and TIA improves risk factors: 36-month results from the randomized controlled NAILED stroke risk factor trial

BackgroundStrategies are needed to improve adherence to the blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) level recommendations after stroke and transient ischemic attack (TIA). We investigated whether nurse-led, telephone-based follow-up that included medication titration was more efficient than usual care in improving BP and LDL-C levels 36 months after discharge following stroke or TIA.MethodsAll patients admitted for stroke or TIA at Östersund hospital that could participate in the telephone-based follow-up were considered eligible. Participants were randomized to either nurse-led, telephone-based follow-up (intervention) or usual care (control). BP and LDL-C were measured one month after discharge and yearly thereafter. Intervention group patients who did not meet the target values received additional follow-up, including lifestyle counselling and medication titration, to reach their treatment goals (BP < 140/90 mmHg, LDL-C < 2.5 mmol/L). The primary outcome was the systolic BP level 36 months after discharge.ResultsOut of 871 randomized patients, 660 completed the 36-month follow-up. The mean systolic and diastolic BP values in the intervention group were 128.1 mmHg (95% CI 125.8–130.5) and 75.3 mmHg (95% CI 73.8–76.9), respectively. This was 6.1 mmHg (95% CI 3.6–8.6, p < 0.001) and 3.4 mmHg (95% CI 1.8–5.1, p < 0.001) lower than in the control group. The mean LDL-C level was 2.2 mmol/L in the intervention group, which was 0.3 mmol/L (95% CI 0.2–0.5, p < 0.001) lower than in controls. A larger proportion of the intervention group reached the treatment goal for BP (systolic: 79.4% vs. 55.3%, p < 0.001; diastolic: 90.3% vs. 77.9%, p < 0.001) as well as for LDL-C (69.3% vs. 48.9%, p < 0.001).ConclusionsCompared with usual care, a nurse-led telephone-based intervention that included medication titration after stroke or TIA improved BP and LDL-C levels and increased the proportion of patients that reached the treatment target 36 months after discharge.Trial registrationISRCTN Registry ISRCTN23868518 (retrospectively registered, June 19, 2012).

Structured tool to improve clinical outcomes of type 2 diabetes mellitus patients: A randomized controlled trial.

Reviewing pharmacist diabetes intervention studies revealed a lack of structured process in providing diabetes care, leading to varied results from increased to minimal improvements. The aim of this study was to determine the effectiveness of the Simpler tool, a structured clinical guidelines tool, in the delivery of diabetes care. The primary outcome was significant improvement in HbA1c. Secondary outcomes were improved lipid profiles and blood pressure (BP). A 6-month parallel multicenter two-arm, single-blind randomized controlled trial involving 14 pharmacists at seven primary care clinics was conducted in Johor, Malaysia. Pharmacists without prior specialized diabetes training were trained to use the tool. Patients were randomized within each center to either Simpler care (SC), receiving care from pharmacists who used the tool (n =55), or usual care (UC), receiving usual care and dispensing services (n = 69). Compared with UC, SC significantly reduced HbA1c (mean reduction 1.59% [95% confidence interval {CI} -2.2, -0.9] vs 0.25% [95% CI -0.62, 0.11], respectively; P ≤ 0.001), and significantly improved systolic BP (-6.28 mmHg [95% CI -10.5, 2.0] vs 0.26 mmHg [95% CI -3.74, 0.43], respectively; P = 0.005). A significantly higher proportion of patients in the SC than UC arm reached the Malaysian guideline treatment goals for HbA1c (14.3% vs 1.5%; P = 0.020), systolic BP (80% vs 42%; P = 0.001), and low-density lipoprotein cholesterol (60.5% vs 40.4%; P = 0.046). Using the Simpler tool facilitated the delivery of comprehensive evidence-based diabetes management and significantly improved clinical outcomes. The Simpler tool supported pharmacists in providing enhanced structured diabetes care.

Estimating the Association of the 2017 and 2014 Hypertension Guidelines With Cardiovascular Events and Deaths in US Adults

The 2017 American College of Cardiology/American Heart Association hypertension guideline recommends lower blood pressure (BP) thresholds for initiating antihypertensive medication and treatment goals than the 2014 evidence-based hypertension guideline. To estimate the potential association of the 2017 and 2014 hypertension guidelines with the proportion of US adults defined as being hypertensive or recommended for antihypertensive treatment and with risk reduction of major cardiovascular disease (CVD) and all-cause mortality. Using data from the National Health and Nutrition Examination Survey 2013 to 2016, we estimated the proportions of US adults with hypertension or recommended for antihypertensive treatment according to the 2017 and 2014 hypertension guidelines. Using data from the National Health and Nutrition Examination Survey, antihypertensive clinical trials, and population-based cohort studies, we estimated risk reductions of CVD and all-cause mortality assuming the entire US adult population achieved guideline-recommended systolic BP (SBP) treatment goals. Data were analyzed between October 2017 and March 2018. Proportions and numbers of individuals with hypertension or recommended for antihypertensive treatment and numbers of CVD and all-cause mortality reduction. According to the 2017 hypertension guideline, the prevalence of hypertension (BP level ≥130/80 mm Hg) was 45.4% (95% CI, 43.9%-46.9%), representing 105.3 (95% CI, 101.9-108.8) million US adults, which was significantly higher than estimates per the 2014 hypertension guideline (BP level ≥140/90 mm Hg): 32.0% (95% CI, 30.3%-33.6%) or 74.1 (95% CI, 70.3-77.9) million individuals, respectively. Additionally, the proportion of individuals recommended for antihypertensive treatment was significantly higher according to the 2017 hypertension guideline (35.9%; 95% CI, 34.2%-37.5%) compared with the 2014 hypertension guideline (31.1%; 95% CI, 29.6%-32.7%). Achieving the 2017 hypertension guideline SBP treatment goals is estimated to reduce 610 000 (95% CI, 496 000-734 000) CVD events and 334 000 (95% CI, 245 000-434 000) total deaths in US adults 40 years and older. Corresponding estimates after achieving the 2014 hypertension guideline SBP treatment goals were 270 000 (95% CI, 202 000-349 000) and 177 000 (95% CI, 123 000-241 000), respectively. Implementing the 2017 hypertension guideline is estimated to increase 62 000 hypotension and 79 000 acute kidney injury or failure events. Compared with the 2014 hypertension guideline, the 2017 hypertension guideline was associated with an increase in the proportion of adults recommended for antihypertensive treatment and a further reduction in major CVD events and all-cause mortality, but a possible increase in the number of adverse events in the United States.

Motivational Interviewing and Medication Review in Coronary Heart Disease (MIMeRiC): Protocol for a Randomized Controlled Trial Investigating Effects on Clinical Outcomes, Adherence, and Quality of Life.

BackgroundPreventive treatment goals for blood pressure and cholesterol levels continue to be unmet for many coronary patients. The effect of drug treatment depends on both its appropriateness and the patients’ adherence to the treatment regimen. There is a need for adherence interventions that have a measurable effect on clinical outcomes.ObjectiveThis study aims to evaluate the effects on treatment goals of an intervention designed to improve patient adherence and treatment quality in secondary prevention of coronary heart disease. A protocol for the prespecified process evaluation of the trial is published separately.MethodsThe Motivational Interviewing and Medication Review in Coronary heart disease (MIMeRiC) trial is a prospective, randomized, outcomes-blinded trial designed to compare individualized follow-up by a clinical pharmacist using motivational interviewing (MI) and medication review with standard follow-up. Patients were randomized to 2 groups after stratification according to their beliefs about medicines. After standard follow-up at the cardiology clinic, patients in the intervention group are seen individually by a clinical pharmacist 2 to 5 times as required over 7 months, at the clinic. The pharmacist reviews each patient’s medication and uses MI to manage any problems with prescribing and adherence. The primary study outcome is the proportion of patients who have reached the treatment goal for low-density lipoprotein cholesterol by 12 months after discharge. Secondary outcomes are the effects on patient adherence, systolic blood pressure, disease-specific quality of life, and health care use.ResultsThe protocol for this study was approved by the Regional Ethics Committee, Linköping, in 2013. Enrollment started in October 2013 and ended in December 2016 when 417 patients had been included. Follow-up data collection will conclude in March 2018. Publication of the primary and secondary outcome results from the MIMeRiC trial is anticipated in 2019.ConclusionsThe MIMeRiC trial will assess the effectiveness of an intervention involving medication reviews and individualized support. The results will inform the continued development of support for this large group of patients who use preventive medicines for lifelong treatment. The design of this adherence intervention is based on a theoretical framework and is the first trial of an intervention that uses beliefs about medicines to individualize the intervention protocol.Trial RegistrationClinicalTrials.gov NCT02102503; https://clinicaltrials.gov/ct2/show/NCT02102503 (Archived by WebCite at http://www.webcitation.org/6x7iUDohy)

Strategies for Achieving Healthy Vascular Aging.

The population is aging rapidly worldwide, which will lead to an increased societal and economic burden of age-associated chronic disease, including cardiovascular diseases.1,2 Cardiovascular diseases remain the leading cause of morbidity and mortality in developed nations, and chronological age is the primary risk factor for cardiovascular diseases.3 Arterial stiffness and blood pressure (BP) both increase with advancing age4–7 and are independent predictors of cardiovascular (CV) events and mortality.8,9 As such, there is strong, ongoing demand for evidence-based strategies that prevent, delay, or reverse age-associated increases in BP and arterial stiffness.10,11 Indeed, the need for new approaches is expected to grow as the burden of age- and accelerated aging-associated cardiovascular dysfunction and disease continues to rise. In this review, we discuss the concept of healthy vascular aging (HVA) with regard to definition and contributing mechanisms, existing and promising HVA-enhancing lifestyle- and pharmacological-based strategies, and future directions. The focus will be primarily on data from observational and intervention studies in humans. Arterial stiffening and increases in BP occur with advancing age4–7 although population-based studies indicate that this is not an inevitable consequence of aging but rather results from an industrialized lifestyle. 12,13 The prevalence of hypertension dramatically increases with advancing age, affecting approximately two thirds of Americans ≥60 years.3 Hypertension is also highly prevalent in populations with chronic disease, including chronic kidney disease (CKD) and type 2 diabetes mellitus.14,15 The most recent Joint National Commission 8 guidelines increased the BP treatment goal for individuals >60 years of age to <150/90 mm Hg with a goal of <140/90 mm Hg in adults 30 to 59 years of age, including individuals with diabetes mellitus and nondiabetic CKD.16 However, the recently completed multicenter randomized controlled trial, …

Personalizing the Intensity of Blood Pressure Control: Modeling the Heterogeneity of Risks and Benefits From SPRINT (Systolic Blood Pressure Intervention Trial).

In SPRINT (Systolic Blood Pressure Intervention Trial), patients with hypertension and high cardiovascular risk treated with intensive blood pressure (BP) control (<120 mm Hg) had fewer major adverse cardiovascular events (MACE) and deaths but higher rates of treatment-related serious adverse events (SAE) than patients randomized to standard BP control (<140 mm Hg). However, the degree of benefit or harm for an individual patient could vary because of heterogeneity in treatment effect. Using patient-level data from 9361 randomized patients in SPRINT, we developed models to predict risk for MACE or death and treatment-related SAE to allow for individualized BP treatment goals based on each patient's projected risk and benefit of intensive versus standard BP control. Models were internally validated using bootstrap resampling and externally validated on 4741 patients from the ACCORD-BP (The Action to Control Cardiovascular Risk in Diabetes blood pressure) trial. Among 9361 SPRINT patients, 755 patients (8.1%) had a MACE or death event and 338 patients (3.6%) had a treatment-related SAE during a median follow-up of 3.3 years. The MACE/death and the SAE model had C statistics of 0.72 and 0.70, respectively, in the derivation cohort and 0.69 and 0.65 in ACCORD. The MACE/death model had 10 variables including treatment interactions with age, baseline systolic BP, and diastolic BP, and the SAE model had 8 variables including treatment interaction with number of BP medications. Intensive BP treatment was associated with a mean 2.2±2.6% lower risk of MACE/death compared with standard treatment (range, 20.7% lower risk to 19.6% greater risk among individual patients) and a mean 2.2±1.2% higher risk for SAEs (range, 0.5%-15.8% more harm in individual patients). To translate the findings from SPRINT to clinical practice, we developed prediction models to tailor the intensity of BP control based on the projected risk and benefit for each unique patient. This approach should be prospectively tested to better engage patients in shared medical decision making and to improve outcomes. URL: https://clinicaltrials.gov. Unique identifier: NCT01206062.

Abstract 003: Personalizing the Intensity of Blood Pressure Control: Modeling the Heterogeneity of Risks and Benefits From the SPRINT Trial

Introduction: In SPRINT (Systolic blood PRessure INtervention Trial), non-diabetic patients with hypertension at high cardiovascular risk treated with intensive blood pressure (BP) control (&lt;120mmHg) had fewer major adverse cardiovascular events (MACE) and all-cause deaths but higher rates of serious adverse events (SAE) compared with patients treated with standard BP control (&lt;140mmHg). However, the degree of benefit or harm for an individual patient could vary due to heterogeneity in treatment effect. Methods: Using patient-level data from SPRINT, we developed predictive models for benefit (freedom from death or MACE) and harm (increased SAE) to allow for individualized BP treatment goals based on projected risk-benefit for each patient. Interactions between candidate variable and treatment were evaluated in the models to identify differential treatment effects. We performed 10 fold cross-validation for both the models. Results: Among 9361 patients, 8606 (92%) patients had no MACE or death event (benefit) and 3529 (38%) patients had a SAE (harm) over a median follow-up of 3.3 years. The benefit model showed good discrimination (c-index= 0.72; cross-validated c-index= 0.72) with treatment interactions of age, sex, and baseline systolic BP (Figure A), with more benefit of intensive BP treatment in patients who are older, male, and have lower baseline SBP. The SAE risk model showed moderate discrimination (c-index=0.66; cross-validated c-index= 0.65) with a treatment interaction of baseline renal function (Figure B), indicating less harm of intensive treatment in patients with a higher baseline creatinine. The mean predicted absolute benefit of intensive BP treatment was of 2.2% ± 2.5% compared with standard treatment, but ranged from 10.7% lower benefit to 17% greater benefit in individual patients. Similarly, mean predicted absolute harm with intensive treatment was 1.0% ± 1.9%, but ranged from 15.9% lesser harm to 4.9% more harm. Conclusion: Among non-diabetic patients with hypertension at high cardiovascular risk, we developed prediction models using basic clinical data that can identify patients with higher likelihood of benefit vs. harm with BP treatment strategies. These models could be used to tailor the treatment approach based on the projected risk and benefit for each unique patient.

What Should the Systolic Blood Pressure Treatment Goal be in Patients Aged 60 Years and Older with Hypertension in 2016?

The Hypertension in the Very Elderly Trial (HYVET) randomized 3, 845 patients aged 80 years and older, mean age 83.6 years, with a systolic blood pressure (SBP) of ≥ 160 mmHg to indapamide plus perindopril if needed versus double-blind placebo [1]. The target SBP reached was 150 mmHg, and the lowest SBP reached was 143 mmHg. Median follow-up was 1.8 years. Compared to patients randomized to placebo, patients randomized to antihypertensive drug therapy had a 30% reduction in fatal or nonfatal stroke, a 39% reduction in fatal stroke, a 21% reduction in all-cause mortality, a 23% reduction in cardiovascular death, and a 64% reduction in heart failure

Coronary Artery Calcium to Guide a Personalized Risk-Based Approach to Initiation and Intensification of Antihypertensive Therapy.

The use of atherosclerotic cardiovascular disease (ASCVD) risk to personalize systolic blood pressure (SBP) treatment goals is a topic of increasing interest. Therefore, we studied whether coronary artery calcium (CAC) can further guide the allocation of anti-hypertensive treatment intensity. We included 3733 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with SBP between 120 and 179 mm Hg. Within subgroups categorized by both SBP (120-139 mm Hg, 140-159 mm Hg, and 160-179 mm Hg) and estimated 10-year ASCVD risk (using the American College of Cardiology/American Heart Assocation pooled-cohort equations), we compared multivariable-adjusted hazard ratios for the composite outcome of incident ASCVD or heart failure after further stratifying by CAC (0, 1-100, or >100). We estimated 10-year number-needed-to-treat for an intensive SBP goal of 120 mm Hg by applying the treatment benefit recorded in meta-analyses to event rates within CAC strata. The mean age was 65 years, and 642 composite events took place over a median of 10.2 years. In persons with SBP <160 mm Hg, CAC stratified risk for events. For example, among those with an ASCVD risk of <15% and who had an SBP of either 120 to 139 mm Hg or 140 to 159 mm Hg, respectively, we found increasing hazard ratios for events with CAC 1 to 100 (1.7 [95% confidence interval, 1.0-2.6] or 2.0 [1.1-3.8]) and CAC >100 (3.0 [1.8-5.0] or 5.7 [2.9-11.0]), all relative to CAC=0. There appeared to be no statistical association between CAC and events when SBP was 160 to 179 mm Hg, irrespective of ASCVD risk level. Estimated 10-year number-needed-to-treat for a SBP goal of 120mmHg varied substantially according to CAC levels when predicted ASCVD risk <15% and SBP <160mmHg (eg, 10-year number-needed-to-treat of 99 for CAC=0 and 24 for CAC>100, when SBP 120-139mm Hg). However, few participants with ASCVD risk <5% had elevated CAC. Furthermore, 10-year number-needed-to-treat estimates were consistently low and varied less among CAC strata when SBP was 160 to 179 mm Hg or when ASCVD risk was ≥15% at any SBP level. Combined CAC imaging and assessment of global ASCVD risk has the potential to guide personalized SBP goals (eg, choosing a traditional goal of 140 or a more intensive goal of 120 mm Hg), particularly among adults with an estimated ASCVD risk of 5% to 15% and prehypertension or mild hypertension.