Control of Blood Pressure and Risk Attenuation: Post Trial Follow-Up of Randomized Groups

<div><p>Background</p><p>Evidence on long term effectiveness of public health strategies for lowering blood pressure (BP) is scarce. In the Control of Blood Pressure and Risk Attenuation (COBRA) Trial, a 2 x 2 factorial, cluster randomized controlled trial, the combined home health education (HHE) and trained general practitioner (GP) intervention delivered over 2 years was more effective than no intervention (usual care) in lowering systolic BP among adults with hypertension in urban Pakistan. However, it was not clear whether the effect would be sustained after the cessation of intervention. We conducted 7 years follow-up inclusive of 5 years of post intervention period of COBRA trial participants to assess the effectiveness of the interventions on BP during extended follow-up.</p><p>Methods</p><p>A total of 1341 individuals 40 years or older with hypertension (systolic BP 140 mm Hg or greater, diastolic BP 90 mm Hg or greater, or already receiving treatment) were followed by trained research staff masked to randomization status. BP was measured thrice with a calibrated automated device (Omron HEM-737 IntelliSense) in the sitting position after 5 minutes of rest. BP measurements were repeated after two weeks. Generalized estimating equations (GEE) were used to analyze the primary outcome of change in systolic BP from baseline to 7- year follow-up. The multivariable model was adjusted for clustering, age at baseline, sex, baseline systolic and diastolic BP, and presence of diabetes.</p><p>Findings</p><p>After 7 years of follow-up, systolic BP levels among those randomised to combined HHE plus trained GP intervention were significantly lower (2.1 [4.1–0.1] mm Hg) compared to those randomised to usual care, (P = 0.04). Participants receiving the combined intervention compared to usual care had a greater reduction in LDL-cholesterol (2.7 [4.8 to 0.6] mg/dl.</p><p>Conclusions</p><p>The benefit in systolic BP reduction observed in the original cohort assigned to the combined intervention was attenuated but still evident at 7- year follow-up. These findings highlight the potential for scaling-up simple strategies for cardiovascular risk reduction in low- and middle- income countries.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT00327574?id=NCT00327574&rank=1" target="_blank">NCT00327574</a></p></div

Study flow diagram.

<p>HHE = Home Health Education; GP = General Practitioner. * One pregnant woman & one man withdrew because of target organ damage & severe debility. † Participants who successfully completed 7 years of follow-up were included in the per protocol analysis. Note: The status of excluded participants at each follow-up is variable except deaths.</p

Comparison of Clusters and Baseline Participant Characteristics among Randomized groups.

<p>* GP = trained general practitioner; HHE = home health education</p><p>† Use of Tobacco (Smoking and Chew). Current users are those who at the time of survey either smoke and/or use pan with tobacco. Past users are those who have smoked <b>≥</b> 100 cigarettes or chewed <b>≥</b> 100 pans in their life time. Never users are those who have smoked <b><</b>100 cigarettes or chewed <b><</b> 100 pans in their life time.</p><p>‡ Physical activity MET (Metabolic Equivalent) Score was defined as: Total MET-minutes/week = Walk (METs-min*days) + Moderate (METs*min*days) + Vigorous (METs*min*days).</p><p>§ Low socioeconomic status defined as monthly household income <$50 as reported by Federal Bureau of Statistics.</p><p>|| Diabetes was defined as patients taking anti diabetic medications, or having fasting blood sugar ≥ 7.0 mmol/L (126 mg/dL). Blood samples were missing in 62 subjects.</p><p>¶ Central obesity was defined as having a waist circumference of ≥ 80 cm in women and ≥ 90 cm in men.</p><p>†† Overweight/Obesity was defined as Asian specific criterion of ≥23 kg/m².</p><p>‡‡ Controlled BP is defined as (systolic BP < 140 & diastolic BP < 90 mm Hg).</p><p><b>§§</b> CVD risk score is computed based on Framingham risk equation based on age, total cholesterol, HDL-cholesterol, systolic BP, antihypertensive therapy status, smoking, and diabetes.</p><p>Comparison of Clusters and Baseline Participant Characteristics among Randomized groups.</p

Outcomes- Blood Pressure Levels and control rates among Randomized Groups at 7 Years.

<p>GP = general practitioner; HHE = home health education.</p><p><b>†</b> Mean follow-up systolic and diastolic BP levels are based on individuals with available BP readings at 7 years post trial follow-up (n = 740)</p><p>^a Change is the difference between baseline minus follow-up with negative sign indicating a decline.</p><p>Adjusted for clustering, time, age, gender, diabetes status, and baseline systolic blood pressure, diastolic blood pressure, or blood pressure control, respectively. P values indicate comparison with usual care (reference). Adjusted risk ratios computed from adjusted marginal probabilities using logistic generalized estimating equations model (Santos, Carlos AST, et al. "Estimating adjusted prevalence ratio in clustered cross-sectional epidemiological data." BMC medical research methodology 8.1 (2008): 80).</p><p>Outcomes- Blood Pressure Levels and control rates among Randomized Groups at 7 Years.</p

Outcomes- Hazard Ratio for All-cause mortality Among Randomized Groups.

<p>HHE = home health education; GP = general practitioner.</p><p>* Unadjusted analysis accounts for clustering</p><p>** Adjusted for clustering, age, gender, baseline systolic BP, baseline diastolic BP, diabetes, and smoking</p><p>Outcomes- Hazard Ratio for All-cause mortality Among Randomized Groups.</p

Effects of endpoint adjudication on the results of ADVANCE blood pressure lowering arm.

<p>Effects of blood pressure lowering treatment on the risks of clinical outcomes were examined based on diagnoses reported by the site investigators (SI) and those assigned by the endpoint adjudication committee (EPAC). Centers of the boxes are placed at the estimates of effect; areas of the boxes are proportional to the reciprocal of the variance of the estimates. Horizontal lines represent 95% confidence intervals (CI).</p

Enrolment, randomisation, and follow-up of study participants.

<p>A total of 11140 patients were randomly assigned, in a 2x2 factorial design, to active blood pressure lowering treatment with perindopril-indapamide or matching placebo, and to a gliclazide-based intensive glucose control strategy or a standard glucose control strategy.</p

Adiposity and risk of decline in glomerular filtration rate: meta-analysis of individual participant data in a global consortium

OBJECTIVE:To evaluate the associations between adiposity measures (body mass index, waist circumference, and waist-to-height ratio) with decline in glomerular filtration rate (GFR) and with all cause mortality. DESIGN:Individual participant data meta-analysis. SETTING:Cohorts from 40 countries with data collected between 1970 and 2017. PARTICIPANTS:Adults in 39 general population cohorts (n=5 459 014), of which 21 (n=594 496) had data on waist circumference; six cohorts with high cardiovascular risk (n=84 417); and 18 cohorts with chronic kidney disease (n=91 607). MAIN OUTCOME MEASURES:GFR decline (estimated GFR decline ≥40%, initiation of kidney replacement therapy or estimated GFR <10 mL/min/1.73 m2) and all cause mortality. RESULTS:Over a mean follow-up of eight years, 246 607 (5.6%) individuals in the general population cohorts had GFR decline (18 118 (0.4%) end stage kidney disease events) and 782 329 (14.7%) died. Adjusting for age, sex, race, and current smoking, the hazard ratios for GFR decline comparing body mass indices 30, 35, and 40 with body mass index 25 were 1.18 (95% confidence interval 1.09 to 1.27), 1.69 (1.51 to 1.89), and 2.02 (1.80 to 2.27), respectively. Results were similar in all subgroups of estimated GFR. Associations weakened after adjustment for additional comorbidities, with respective hazard ratios of 1.03 (0.95 to 1.11), 1.28 (1.14 to 1.44), and 1.46 (1.28 to 1.67). The association between body mass index and death was J shaped, with the lowest risk at body mass index of 25. In the cohorts with high cardiovascular risk and chronic kidney disease (mean follow-up of six and four years, respectively), risk associations between higher body mass index and GFR decline were weaker than in the general population, and the association between body mass index and death was also J shaped, with the lowest risk between body mass index 25 and 30. In all cohort types, associations between higher waist circumference and higher waist-to-height ratio with GFR decline were similar to that of body mass index; however, increased risk of death was not associated with lower waist circumference or waist-to-height ratio, as was seen with body mass index. CONCLUSIONS:Elevated body mass index, waist circumference, and waist-to-height ratio are independent risk factors for GFR decline and death in individuals who have normal or reduced levels of estimated GFR

Identification of four independent LD blocks in the 8p23.1 region <i>(~3</i>.<i>3 MBs</i>).

<p>Identification of four independent LD blocks in the 8p23.1 region <i>(~3</i>.<i>3 MBs</i>).</p