Raymond R. Townsend

Persons with chronic kidney disease (CKD) are at high risk of infection. While low-grade inflammation could impair immune response, it is unknown whether inflammatory markers are associated with infection risk in this clinical population. Using 2003–2013 data from the Chronic Renal Insufficiency Cohort Study (3,597 participants with CKD), we assessed the association of baseline plasma levels of 4 inflammatory markers (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1 receptor antagonist (IL-1RA), and transforming growth factor-β (TGF-β)) with incident hospitalization with major infection (pneumonia, urinary tract infection, cellulitis and osteomyelitis, and bacteremia and sepsis). During follow-up (median 7.5 years), 36% (n = 1,290) had incident hospitalization with major infection. In multivariable Cox analyses with each inflammatory marker modeled as a restricted cubic spline, higher levels of IL-6 and TNF-α were monotonically associated with increased risk of hospitalization with major infection (for 95th vs. 5th percentile, hazard ratio = 2.11 (95% confidence interval: 1.68, 2.66) for IL-6 and 1.88 (95% confidence interval: 1.51, 2.33) for TNF-α), while corresponding associations for IL-1RA or TGF-β were nonsignificant. Thus, higher plasma levels of IL-6 and TNF-α, but not IL-1RA or TGF-β, were significantly associated with increased risk of hospitalization with major infection. Future studies should investigate whether inflammatory pathways that involve IL-6 and TNF-α increase susceptibility to infection among individuals with CKD.

Background: Short sleep duration has been widely linked to increased cardiovascular morbidity and mortality, although the underlying mechanisms for this relationship remain unclear. Maladaptive circadian variations in blood pressure (BP) may be an important mediator of adverse outcomes in people with short sleep duration. Our goal was to evaluate the association between sleep duration and 24-hour BP control. Methods: We performed a post-hoc analyses of 24-hour ambulatory BP monitoring in 219 non-hypertensive and pre-hypertensive adults in the Lifestyle Modification in BP Lowering Study (LIMBS) and Penn Icelandic Sleep Apnea (PISA) Study. Results: The 24-hour mean systolic BP was 12.7 mmHg higher in LIMBS (see Figure; pConclusions: Shorter sleep duration is strongly associated with higher systolic BP on 24-hour ambulatory BP monitoring; the association seems to be independent of nocturnal and in-office BP. Adults with shorter sleep duration may benefit from screening with 24-hour ambulatory BP monitoring to promote earlier detection of hypertension and potentially mitigate their increased risk for future cardiovascular disease.

Background: Physiologic determinants, such as pulse pressure [difference between systolic blood pressure (SBP) and diastolic BP (DBP)], mean arterial pressure (2/3 DBP + 1/3 SBP), and double product [beats per minute (bpm) × SBP], are linked to cardiovascular outcomes. The effects of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, on pulse pressure, mean arterial pressure, and double product were assessed in patients with type 2 diabetes mellitus (T2DM). Methods: This post hoc analysis was based on pooled data from four 26-week, randomized, double-blind, placebo-controlled studies evaluating canagliflozin in patients with T2DM (N = 2313) and a 6-week, randomized, double-blind, placebo-controlled, ambulatory BP monitoring (ABPM) study evaluating canagliflozin in patients with T2DM and hypertension (N = 169). Changes from baseline in SBP, DBP, pulse pressure, mean arterial pressure, and double product were assessed using seated BP measurements (pooled studies) or averaged 24-h BP assessments (ABPM study). Safety was assessed based on adverse event reports. Results: In the pooled studies, canagliflozin 100 and 300 mg reduced SBP (−4.3 and −5.0 vs −0.3 mmHg) and DBP (−2.5 and −2.4 vs −0.6 mmHg) versus placebo at week 26. Reductions in pulse pressure (−1.8 and −2.6 vs 0.2 mmHg), mean arterial pressure (−3.1 and −3.3 vs −0.5 mmHg), and double product (−381 and −416 vs −30 bpm × mmHg) were also seen with canagliflozin 100 and 300 mg versus placebo. In the ABPM study, canagliflozin 100 and 300 mg reduced mean 24-h SBP (−4.5 and −6.2 vs −1.2 mmHg) and DBP (−2.2 and −3.2 vs −0.3 mmHg) versus placebo at week 6. Canagliflozin 300 mg provided reductions in pulse pressure (−3.3 vs −0.8 mmHg) and mean arterial pressure (−4.2 vs −0.6 mmHg) compared with placebo, while canagliflozin 100 mg had more modest effects on these parameters. Canagliflozin was generally well tolerated in both study populations. Conclusions: Canagliflozin improved all three cardiovascular physiologic markers, consistent with the hypothesis that canagliflozin may have beneficial effects on some cardiovascular outcomes in patients with T2DM. Trial registration ClinicalTrials.gov Identifier: NCT01081834 (registered March 2010); NCT01106677 (registered April 2010); NCT01106625 (registered April 2010); NCT01106690 (registered April 2010); NCT01939496 (registered September 2013)

The effect of clinic-based intensive hypertension treatment on ambulatory blood pressure (BP) is unknown. The goal of the SPRINT (Systolic Blood Pressure Intervention Trial) ambulatory BP ancillary study was to evaluate the effect of intensive versus standard clinic-based BP targets on ambulatory BP. Ambulatory BP was obtained within 3 weeks of the 27-month study visit in 897 SPRINT participants. Intensive treatment resulted in lower clinic systolic BP (mean difference between groups=16.0 mm Hg; 95% confidence interval, 14.1–17.8 mm Hg), nighttime systolic BP (mean difference=9.6 mm Hg; 95% confidence interval, 7.7–11.5 mm Hg), daytime systolic BP (mean difference=12.3 mm Hg; 95% confidence interval, 10.6–13.9 mm Hg), and 24-hour systolic BP (mean difference=11.2 mm Hg; 95% confidence interval, 9.7–12.8 mm Hg). The night/day systolic BP ratio was similar between the intensive (0.92±0.09) and standard-treatment groups (0.91±0.09). There was considerable lack of agreement within participants between clinic systolic BP and daytime ambulatory systolic BP with wide limits of agreement on Bland–Altman plots. In conclusion, targeting a systolic BP of <120 mm Hg, when compared with <140 mm Hg, resulted in lower nighttime, daytime, and 24-hour systolic BP, but did not change the night/day systolic BP ratio. Ambulatory BP monitoring may be required to assess the effect of targeted hypertension therapy on out of office BP. Further studies are needed to assess whether targeting hypertension therapy based on ambulatory BP improves clinical outcomes. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01835249.

The use of arterial stiffness measurements in longitudinal cohorts of normal populations, hypertensive patients, diabetic patients, healthy elderly, and patients on hemodialysis have confirmed the value of this important measure of arterial health, and established its complementary role to measures of blood pressure. Its contribution to understanding cardiovascular and mortality risk beyond blood pressure measurements has moved measures of arterial stiffness into the ranks of factors such as elevated cholesterol, diabetes, and left ventricular hypertrophy in considering cardiovascular risk. The recent international collaboration's publication of reference ranges for normal people and those with hypertension, along with the American Heart Association's recent scientific statement on standardizing arterial stiffness measurements are important aspects to consider in future studies employing these valuable methods, particularly as interventions that not only lower blood pressure but improve arterial function are tested in the clinical arena.

This randomized, double‐blind, placebo‐controlled study evaluated the early effects of canagliflozin on blood pressure (BP) in patients with type 2 diabetes mellitus (T2DM) and hypertension. Patients were randomized to canagliflozin 300 mg, canagliflozin 100 mg, or placebo for 6 weeks and underwent 24‐hour ambulatory BP monitoring before randomization, on day 1 of treatment, and after 6 weeks. The primary endpoint was change in mean 24‐hour systolic BP (SBP) from baseline to week 6. Overall, 169 patients were included (mean age, 58.6 years; glycated hemoglobin, 8.1%; seated BP 138.5/82.7 mm Hg). At week 6, canagliflozin 300 mg provided greater reductions in mean 24‐hour SBP than placebo (least squares mean −6.2 vs −1.2 mm Hg, respectively; P=.006). Numerical reductions in SBP were observed with canagliflozin 100 mg. Canagliflozin was generally well tolerated, with side effects similar to those reported in previous studies. These results suggest that canagliflozin rapidly reduces BP in patients with T2DM and hypertension.

Resistant hypertension affects approximately 10–15 % of the hypertensive population and is associated with an increased occurrence of adverse cardiovascular outcomes. Recently, renal denervation (RDN) has emerged as a novel, non-pharmacologic therapy for resistant hypertension that is designed to ablate the sympathetic nerves distributed around the renal arteries, thus diminishing sympathetic nervous system activity and its influence on hypertension. RDN appeared to have a powerful BP-lowering effect in early clinical trials. However, a pivotal follow-up trial, SYMPLICITY HTN-3, showed no additional benefit of the therapy when compared with a sham procedure. Various aspects of the trial have been examined to explain this inconsistency, including a potent placebo effect and uncertainty about whether RDN actually occurred. Further research is needed to clarify the role of RDN in the management of resistant hypertension.