ATEMPTing to navigate between “lower is better” and “less is more”

The Impact of APOL1 on Chronic Kidney Disease and Hypertension.

Blood Pressure Goals: How Low Is Safe in CKD?

Aggressive blood pressure reduction and renin–angiotensin system blockade in chronic kidney disease: time for re-evaluation?

ABSTRACTBackgroundThe effects of intensive blood pressure (BP) control on adverse kidney outcomes remain undetermined.MethodsThis post hoc analysis included the Systolic Blood Pressure Intervention Trial (SPRINT) participants and the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD‐BP) participants receiving standard glucose‐lowering treatment and satisfying SPRINT eligibility criteria. The risks of kidney events between intensive (systolic BP < 120 mmHg) and standard (systolic BP < 140 mmHg) controls in participants with or without baseline chronic kidney disease (CKD) were compared using Cox proportional hazards models.ResultsA total of 10,946 participants (2724 with CKD and 8222 without CKD) were included. During the intervention and post‐intervention periods, the risk of renal failure was either reduced by intensive BP control in participants with CKD (HR = 0.46; 95% CI = 0.22–0.97) or was not significantly different between intensive and standard BP control in participants without CKD (HR = 0.88, 95% CI = 0.52–1.49; pinteraction = 0.128). The risk of ≥ 30% reduction in estimated glomerular filtration rate (eGFR) was increased and the risk of albuminuria was decreased by intensive BP control in participants with or without CKD. Intensive BP control increased the risk of CKD progression to moderate‐ or high‐risk category, but not to very‐high risk category according to the Kidney Disease Improving Global Outcomes (KDIGO) risk categories.ConclusionsThe intensive BP control might increase the risk of mild CKD progression but not of more advanced CKD progression or renal failure compared with the standard BP control.

Physical Activity and Diabetes.

Background The Systolic Blood Pressure Intervention Trial (SPRINT) found that intensive versus standard blood pressure (BP) control reduced cardiovascular (CV) morbidity and mortality in high-risk patients. Although antihypertensive therapies were provided at no cost to trial participants, patients were covered by various entities. Insurance coverage provides a unique dimension of risk assessment and may provide additional prognostic information in this setting. Purpose To assess the risks of incident CV events and safety events in a high CV risk population according to type of health insurance, and to assess if insurance type interacted with the effect of intensive versus standard BP control. Methods SPRINT was a randomized, controlled trial conducted across 102 US sites of 9,361 high-risk adults ≥50 years, without diabetes, and with a systolic BP 130–180 mmHg at screening. Study participants were randomized to intensive (target systolic BP &amp;lt;120mmHg) or standard BP control (target systolic BP &amp;lt;140mmHg) and followed for median 3.2 years (range 0–4.8 years). The primary efficacy endpoint was the composite of acute coronary syndromes, stroke, heart failure, or CV death. The primary safety endpoint was the composite of serious adverse events. The risk of efficacy and safety events according to type of health insurance, including the effect of intensive BP control in each subgroup, was evaluated using multivariable Cox proportional-hazards regression with interaction analyses. Private/other insurance type served as the reference group. Results Of 9361 participants, 3980 (42.5%) were covered by private/other insurance, 1483 (15.8%) by a Veterans Affairs (VA) health plan, 2691 (28.8%) by Medicare, 207 (2.2%) by Medicaid, and 1000 (10.7%) were uninsured. Insurance coverage distribution was well-balanced between the two study arms (P&amp;gt;0.05). Compared with patients who had private/other insurance, the risk of the primary endpoint was significantly higher among Medicaid beneficiaries (adj. hazard ratio [HR], 1.81, 95% confidence interval [CI], 1.09–3.00; P=0.02). The risk of death was similarly highest among Medicaid patients (adj. HR, 2.08, 95% CI, 1.08–4.02; P=0.03) and was also significantly higher among VA patients (adj. HR, 1.49, 95% CI, 1.11–2.99; P=0.008) (Figure). Serious adverse events were more common in the VA population (HR, 1.12, 95% CI, 1.01–1.23; P=0.03). Insurance type did not modify the efficacy and safety of intensive BP control (P&amp;gt;0.05 for all interactions). Conclusions In SPRINT, Medicaid beneficiaries were at significantly greater risk for experiencing a primary CV event. Medicaid patients and VA patients both had higher mortality than those covered by private/other insurance. The risks and benefits of intensive BP control were not affected by insurance type. Funding Acknowledgement Type of funding sources: None. Risk of death and health insurace type

Introduction: Intensive blood pressure (BP) control is associated with a significant reduction in the risk of heart failure (HF) or all-cause death. However, the extent to which intensive BP control-associated HF risk reduction is mediated by changes in subclinical markers of cardiovascular (CV) disease (CVD) and stage B HF is not well-characterized. Methods: Participants of the Systolic Blood Pressure Intervention Trial (SPRINT) with hypertension and available data on subclinical CVD markers at baseline and follow-up (1- or 2-year visit) were included. The key subclinical markers of CVD analyzed included chronic myocardial injury (assessed by high-sensitivity cardiac troponin I [hs-cTnI]), neurohormonal stress (assessed by N-terminal pro-B-type natriuretic peptide [NT-proBNP]), left ventricular (LV) mass (assessed by electrocardiogram Cornell voltage [CV]), and arterial stiffness (assessed by estimated pulse wave velocity [ePWV]). A counterfactual framework was used to assess the effects of the exposure and mediator on key outcomes, including 1) HF / all-cause death; 2) atherosclerotic CVD (ASCVD), including nonfatal myocardial infarction, nonfatal stroke, or CV death. Results: The present study included 8,872 participants (35% women, 31% Black). Over the 3.3-year median follow-up, there were 333 (3.8%) HF / all-cause death events and 200 (2.3%) ASCVD events. Reductions in neurohormonal stress and LV mass mediated up to 15% of the reduction in risk of HF / all-cause death with intensive BP control (Table). In contrast, treatment-related changes in chronic myocardial injury and arterial stiffness did not mediate the benefits of intensive BP reduction on HF / all-cause death risk. Furthermore, changes in any subclinical CVD markers did not mediate the effect of intensive BP control on ASCVD risk (Table). Conclusions: In this post-hoc analysis of SPRINT, improvements in neurohormonal stress and LV mass, as identified by surrogate markers of hs-cTnI and CV, were important mediators of the beneficial effects of intensive BP control in reducing the risk of HF / all-cause death. Mediators of the effect of intensive vs. standard BP control for reducing HF / all-cause death differ from those for ASCVD.

Although guidelines recommend strict blood pressure (BP) control in patients with type 2 diabetes mellitus (T2DM) and elevated cardiovascular risk, the long-term effects of this approach are unknown. We investigated the effect of intensive BP control on clinical outcomes in patients with T2DM over 9 years of follow-up. We included Action to Control Cardiovascular Risk in Diabetes - Blood Pressure participants in the standard glucose control arm who had established cardiovascular disease, chronic kidney disease, were ≥75 years of age or who had a 10-year coronary heart risk ≥15%. Participants were randomized to either intensive (systolic BP < 120 mm Hg) or standard (systolic BP < 140 mm Hg) BP control for an average of 5 years. Observational follow-up occurred for an average of 4 years thereafter. After an average total follow-up of 9 years, intensive BP control reduced the composite of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke by 25% (hazard ratio, 0.75; 95% confidence interval, 0.60-0.95; P = .02). The overall benefit was driven by a reduction in nonfatal myocardial infarction (P = .01). In this post-hoc analysis, the benefits of a fixed-duration intensive BP control intervention in patients with T2DM persisted throughout 9 years of follow-up.

Sarcopenia and hypertension are independently associated with worse cardiovascular disease (CVD) risk and survival. While individuals with sarcopenia may benefit from intensive blood pressure (BP) control, the increased vulnerability of this population raises concerns for potential harm. This study aimed to evaluate clinical and safety outcomes with intensive (target <120 mm Hg) versus standard (<140 mm Hg) systolic BP targets in older hypertensive adults with sarcopenia compared with nonsarcopenic counterparts in the SPRINT (Systolic Blood Pressure Intervention Trial). Sarcopenia was defined using surrogates of the lowest sex-stratified median of the sarcopenia index (serum creatinine/cystatin C×100) for muscle wasting and gait speed ≤0.8 m/s for muscle weakness. Outcomes included CVD events, all-cause mortality, and serious adverse events. Of 2571 SPRINT participants with sarcopenia index and gait speed data available (aged ≥75 years), 502 (19.5%) met the criteria for sarcopenia, which was associated with higher risks of CVD events (adjusted hazard ratio, 1.49 [95% CI, 1.15-1.94]; P=0.003) and all-cause mortality (adjusted hazard ratio, 1.46 [95% CI, 1.09-1.94]; P=0.010). In participants with sarcopenia, intensive (versus standard) BP control nearly halved the risk of CVD events (adjusted hazard ratio, 0.57 [95% CI, 0.36-0.88]; P=0.012) without increasing serious adverse events. Similar risk reduction was seen for all-cause mortality in participants with sarcopenia (adjusted hazard ratio, 0.66 [95% CI, 0.41-1.08]; P=0.102), but the effect was only significant in those without chronic kidney disease. Older hypertensive adults with sarcopenia randomized to intensive BP control experienced a lower risk of CVD without increased adverse events compared with standard BP control. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.

Comparison of Frequency of Atherosclerotic Cardiovascular and Safety Events With Systolic Blood Pressure <120mm Hg Versus 135-139mm Hg in a Systolic Blood Pressure Intervention Trial Primary Prevention Subgroup

[Figure: see text].

Blood pressure as a potential biomarker of the efficacy angiogenesis inhibitor

Optimizing Medication Use in Older Adults

Background: There is no evidence from randomized trials to support a standard strategy of lowering systolic blood pressure below 140 mm Hg in persons with type 2 diabetes mellitus. We investigated whether intensive therapy targeting normal systolic pressure (i.e., &lt;120 mm Hg) reduces major cardiovascular events in participants with type 2 diabetes at high risk for cardiovascular events. Methods: We systematically searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) comparing the impact of intensive versus standard blood pressure control in patients with type 2 diabetes mellitus with the primary outcome of interest being all-cause mortality. We pooled risk ratio and their 95% confidence intervals (CIs). We also examined heterogeneity using I 2 statistics and studies with high heterogeneity were examined using the random-effect model. Results: We included 8 RCTs consisting of 23,121 patients with type 2 diabetes mellitus of which 11,926 (51.6%) had intensive blood pressure treatment while 11,195 (48.4%) had standard blood pressure treatment. The mean age of the included studies was 59.6 years and 56.6% were males. There were no significant differences between groups for all-cause mortality (RR = 0.91; 95% CI [0.82, 1.02]; I 2 = 17.8%; p = 0.104; Figure 1), cardiovascular death (RR = 0.87; 95% CI [0.62, 1.23]; I 2 = 35.6%; p = 0.427), heart failure (RR = 0.84; 95% CI [0.70, 1.00]; I 2 = 0%; p = 0.045) and myocardial infarction (RR = 0.75; 95% CI [0.55, 1.03]; I 2 = 57.1%; p = 0.077). However, intensive blood pressure control significantly reduced the incidence of stroke (RR = 0.56; 95% CI [0.41, 0.75]; I 2 = 64.3%; p &lt; 0.001) compared to standard treatment. Conclusions: Intensive blood pressure control did not reduce all-cause mortality, cardiovascular death, heart failure and myocardial infarction despite reducing the incidence of stroke.

Uric Acid: A Clearer Focus