Central Blood Pressure and Chronic Kidney Disease Progression

Hypertension, diabetes, and proteinuria are well-recognized risk factors for progressive kidney function loss. However, despite excellent antihypertensive and antidiabetic drug therapies, which also often lower urinary protein excretion, there remains a significant reservoir of patients with chronic kidney disease who are at high risk for progression to end-stage kidney disease. This has led to the search for less traditional cardiovascular risk factors that will help stratify patients at risk for more rapid kidney disease progression. Among these are noninvasive estimates of vascular structure and function. Arterial stiffness, manifested by the pulse wave velocity in the aorta, has been established in a number of studies as a significant risk factor for kidney disease progression and cardiovascular endpoints. Much less well studied in chronic kidney disease are measures of central arterial pressures. In this paper we cover the physiology behind the generation of the central pulse wave contour and the studies available using these approaches and conclude with some speculations on the rationale for why measurements of central pressure may be informative for the study of chronic kidney disease progression

Impact of diabetes mellitus on ventricular structure, arterial stiffness, and pulsatile hemodynamics in heart failure with preserved ejection fraction

Background-Heterogeneity in the underlying processes that contribute to heart failure with preserved ejection fraction (HFpEF) is increasingly recognized. Diabetes mellitus is a frequent comorbidity in HFpEF, but its impact on left ventricular and arterial structure and function in HFpEF is unknown. Methods and Results-Weassessed the impact of diabetesmellitus on left ventricular cellular and interstitial hypertrophy (assessedwith cardiacmagnetic resonance imaging, including T1mapping pregadolinium and postgadolinium administration), arterial stiffness (assessed with arterial tonometry), and pulsatile arterial hemodynamics (assessed with in-office pressure-flow analyses and 24-hour ambulatory monitoring) among 53 subjects with HFpEF (32 diabetic and 21 nondiabetic subjects). Despite few differences in clinical characteristics, diabetic subjects with HFpEF exhibited a markedly greater left ventricular mass index (78.1 [95% CI, 70.4-85.9] g versus 63.6 [95% CI, 55.8-71.3] g; P=0.0093) and indexed extracellular volume (23.6 [95% CI, 21.2-26.1] mL/m(2) versus 16.2 [95% CI, 13.1-19.4] mL/m(2); P=0.0008). Pronounced aortic stiffening was also observed in the diabetic group (carotid-femoral pulse wave velocity, 11.86 [95% CI, 10.4-13.1] m/s versus 8.8 [95% CI, 7.5-10.1] m/s; P=0.0027), with an adverse pulsatile hemodynamic profile characterized by increased oscillatory power (315 [95% CI, 258-373] mWversus 190 [95% CI, 144-236] mW; P=0.0007), aortic characteristic impedance (0.154 [95% CI, 0.124-0.183] mmHg/mL per second versus 0.096 [95% CI, 0.072-0.121] mm Hg/mL per second; P=0.0024), and forward (59.5 [95% CI, 52.8-66.1] mm Hg versus 40.1 [95% CI, 31.6-48.6] mm Hg; P=0.0010) and backward (19.6 [95% CI, 16.2-22.9] mm Hg versus 14.1 [95% CI, 10.9-17.3] mm Hg; P=0.0169) wave amplitude. Abnormal pulsatile hemodynamics were also evident in 24-hour ambulatory monitoring, despite the absence of significant differences in 24-hour systolic blood pressure between the groups. Conclusions-Diabetes mellitus is a key determinant of left ventricular remodeling, arterial stiffness, adverse pulsatile hemodynamics, and ventricular-arterial interactions in HFpEF

Role of Ambulatory and Home Blood Pressure Monitoring in Clinical Practice: A Narrative Review

Hypertension, a common risk factor for cardiovascular disease, is usually diagnosed and treated based on blood pressure readings obtained in the clinic setting. Blood pressure may differ considerably when measured inside versus outside of the clinic setting. Over the past several decades, evidence has accumulated on the following 2 approaches for measuring blood pressure outside of the clinic: ambulatory blood pressure monitoring (ABPM) and home blood pressure monitoring (HBPM). Both of these methods have a stronger association with cardiovascular disease outcomes than clinic blood pressure measurement. Controversy exists about whether ABPM or HBPM is superior for estimating risk for cardiovascular disease and under what circumstances these methods should be used in clinical practice for assessing blood pressure outside of the clinic. This review describes ABPM and HBPM procedures, the blood pressure phenotypic measurements that can be ascertained, and the evidence that supports the use of each approach to measuring blood pressure outside of the clinic. It also describes barriers to the successful implementation of ABPM and HBPM in clinical practice, proposes core competencies for the conduct of these procedures, and highlights important areas for future research

Late systolic central hypertension as a predictor of incident heart failure : the Multi-Ethnic Study of Atherosclerosis

Background: Experimental studies demonstrate that high aortic pressure in late systole relative to early systole causes greater myocardial remodeling and dysfunction, for any given absolute peak systolic pressure. Methods and Results: We tested the hypothesis that late systolic hypertension, defined as the ratio of late (last one third of systole) to early (first two thirds of systole) pressure-time integrals (PTI) of the aortic pressure waveform, independently predicts incident heart failure (HF) in the general population. Aortic pressure waveforms were derived from a generalized transfer function applied to the radial pressure waveform recorded noninvasively from 6124 adults. The late/early systolic PTI ratio (L/ESPTI) was assessed as a predictor of incident HF during median 8.5 years of follow-up. The L/ESPTI was predictive of incident HF (hazard ratio per 1% increase= 1.22; 95% CI= 1.15 to 1.29; P58.38%) was more predictive of HF than the presence of hypertension. After adjustment for each other and various predictors of HF, the HR associated with hypertension was 1.39 (95% CI= 0.86 to 2.23; P=0.18), whereas the HR associated with a high L/E was 2.31 (95% CI=1.52 to 3.49; P<0.0001). Conclusions: Independently of the absolute level of peak pressure, late systolic hypertension is strongly associated with incident HF in the general population

Isosorbide dinitrate, with or without hydralazine, does not reduce wave reflections, left ventricular hypertrophy, or myocardial fibrosis in patients with heart failure with preserved ejection fraction

Background-Wave reflections, which are increased in patients with heart failure with preserved ejection fraction, impair diastolic function and promote pathologic myocardial remodeling. Organic nitrates reduce wave reflections acutely, but whether this is sustained chronically or affected by hydralazine coadministration is unknown. Methods and Results-We randomized 44 patients with heart failure with preserved ejection fraction in a double-blinded fashion to isosorbide dinitrate (ISDN; n=13), ISDN+hydralazine (ISDN+hydral; n=15), or placebo (n=16) for 6months. The primary end point was the change in reflection magnitude (RM; assessed with arterial tonometry and Doppler echocardiography). Secondary end points included change in left ventricular mass and fibrosis, measured with cardiac magnetic resonance imaging, and the 6-minute walk distance. ISDN reduced aortic characteristic impedance (mean baseline=0.15 [95% CI, 0.14-0.17], 3 months=0.11 [95% CI, 0.10-0.13], 6 months=0.10 [95% CI, 0.08-0.12] mmHg/mL per second; P=0.003) and forward wave amplitude (P-f, mean baseline=54.8 [95% CI, 47.6-62.0], 3 months=42.2 [95% CI, 33.2-51.3]; 6 months=37.0 [95% CI, 27.2-46.8] mmHg, P=0.04), but had no effect on RM (P=0.64), left ventricular mass (P=0.33), or fibrosis (P=0.63). ISDN+hydral increased RM (mean baseline=0.39 [95% CI, 0.35-0.43]; 3 months=0.31 [95% CI, 0.25-0.36]; 6 months=0.44 [95% CI, 0.37-0.51], P=0.03), reduced 6-minute walk distance (mean baseline=343.3 [95% CI, 319.2-367.4]; 6 months=277.0 [95% CI, 242.7-311.4] meters, P=0.022), and increased native myocardial T1 (mean baseline=1016.2 [95% CI, 1002.7-1029.7]; 6 months=1054.5 [95% CI, 1036.5-1072.3], P=0.021). A high proportion of patients experienced adverse events with active therapy (ISDN=61.5%, ISDN+hydral=60.0%; placebo=12.5%; P=0.007). Conclusions-ISDN, with or without hydralazine, does not exert beneficial effects on RM, left ventricular remodeling, or submaximal exercise and is poorly tolerated. ISDN+hydral appears to have deleterious effects on RM, myocardial remodeling, and submaximal exercise. Our findings do not support the routine use of these vasodilators in patients with heart failure with preserved ejection fraction

Arterial stiffness and wave reflection 1 year after a pregnancy complicated by hypertension.

Hypertensive disorders of pregnancy (HDP) are associated with cardiovascular disease (CVD) later in life. The authors investigated the association of HDP with blood pressure (BP) and arterial stiffness 1-year postpartum. Seventy-four participants, 33 with an HDP and 41 with uncomplicated pregnancies, were examined using applanation tonometry to measure BP, carotid-femoral pulse wave velocity (cfPWV), and augmentation index (AIx). On average, women with HDP had a 9 mm higher systolic BP (

Effects of Arteriovenous Fistula on Blood Pressure in Patients With End-Stage Renal Disease: A Systematic Meta-Analysis

Background Central arteriovenous fistula ( AVF ) creation is under investigation for treatment of severe hypertension. We evaluated the effects of AVF for initiation of hemodialysis on systolic, diastolic, and mean arterial blood pressure in patients with end-stage renal disease. Methods and Results Data search included PubMed, Web of Science, and the Cochrane Library. A systematic review and meta-analysis of peer-reviewed studies reporting the effects of the creation/ligation of an AVF on blood pressure in patients with end-stage renal disease was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis), PRISMA -P (PRISMA for systematic review protocols), and ROBINS-I (Risk of Bias in Non-Randomized Studies) criteria by the Cochrane Bias Methods Group. All studies in which the results could have been biased by hemodialysis were excluded. A total of 14 trials including 412 patients with end-stage renal disease ( AVF creation, n=185; AVF ligation, n=227) fulfilled the criteria and were subsequently analyzed. Average blood pressure in patients with no/closed AVF was 140.5/77.6 mm Hg with a mean arterial blood pressure of 96.1 mm Hg. Following creation of AVF , systolic blood pressure significantly decreased by 8.7 mm Hg ( P<0.001), diastolic blood pressure by 5.9 mm Hg ( P<0.001), and mean arterial blood pressure by 6.6 mm Hg ( P=0.02), whereas after ligation systolic blood pressure increased by 5.2 mm Hg ( P=0.07), diastolic blood pressure by 3.8 mm Hg ( P=0.02), and mean arterial blood pressure by 3.7 mm Hg ( P=0.07) during short- to long-term follow-up. Conclusions Creation of AVF significantly decreases blood pressure in patients with end-stage renal disease, whereas blood pressure tends to increase after ligation. These findings illustrate the hemodynamic consequences of AVF which are under investigation for severe hypertension

Ankle Brachial Index and Subsequent Cardiovascular Disease Risk in Patients With Chronic Kidney Disease

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139089/1/jah31554.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139089/2/jah31554_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139089/3/jah31554-sup-0001-TableS1.pd

Research-based versus clinical serum creatinine measurements and the association of acute kidney injury with subsequent kidney function: findings from the Chronic Renal Insufficiency Cohort study.

Background:Observational studies relying on clinically obtained data have shown that acute kidney injury (AKI) is linked to accelerated chronic kidney disease (CKD) progression. However, prior reports lacked uniform collection of important confounders such as proteinuria and pre-AKI kidney function trajectory, and may be susceptible to ascertainment bias, as patients may be more likely to undergo kidney function testing after AKI. Methods:We studied 444 adults with CKD who participated in the prospective Chronic Renal Insufficiency Cohort (CRIC) Study and were concurrent members of a large integrated healthcare delivery system. We estimated glomerular filtration rate (eGFR) trajectories using serum creatinine measurements from (i) the CRIC research protocol (yearly) and (ii) routine clinical care. We used linear mixed effects models to evaluate the associations of AKI with acute absolute change in eGFR and post-AKI eGFR slope, and explored whether these varied by source of creatinine results. Models were adjusted for demographic characteristics, diabetes status and albuminuria. Results:During median follow-up of 8.5 years, mean rate of eGFR loss was -0.31 mL/min/1.73&nbsp;m2/year overall, and 73 individuals experienced AKI (55% Stage 1). A significant interaction existed between AKI and source of serum creatinine for acute absolute change in eGFR level after discharge; in contrast, AKI was independently associated with a faster rate of eGFR decline (mean additional loss of -0.67 mL/min/1.73&nbsp;m2/year), which was not impacted by source of serum creatinine. Conclusions:AKI is independently associated with subsequent steeper eGFR decline regardless of the serum creatinine source used, but the strength of association is smaller than observed in prior studies after taking into account key confounders such as pre-AKI eGFR slope and albuminuria

Cardiac Biomarkers and Risk of Atrial Fibrillation in Chronic Kidney Disease: The CRIC Study.

Background We tested associations of cardiac biomarkers of myocardial stretch, injury, inflammation, and fibrosis with the risk of incident atrial fibrillation (AF) in a prospective study of chronic kidney disease patients. Methods and Results The study sample was 3053 participants with chronic kidney disease in the multicenter CRIC (Chronic Renal Insufficiency Cohort) study who were not identified as having AF at baseline. Cardiac biomarkers, measured at baseline, were NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity troponin T, galectin-3, growth differentiation factor-15, and soluble ST-2. Incident AF ("AF event") was defined as a hospitalization for AF. During a median follow-up of 8 years, 279 (9%) participants developed a new AF event. In adjusted models, higher baseline log-transformed NT-proBNP (N-terminal pro-B-type natriuretic peptide) was associated with incident AF (adjusted hazard ratio [HR] per SD higher concentration: 2.11; 95% CI, 1.75, 2.55), as was log-high-sensitivity troponin T (HR 1.42; 95% CI, 1.20, 1.68). These associations showed a dose-response relationship in categorical analyses. Although log-soluble ST-2 was associated with AF risk in continuous models (HR per SD higher concentration 1.35; 95% CI, 1.16, 1.58), this association was not consistent in categorical analyses. Log-galectin-3 (HR 1.05; 95% CI, 0.91, 1.22) and log-growth differentiation factor-15 (HR 1.16; 95% CI, 0.96, 1.40) were not significantly associated with incident AF. Conclusions We found strong associations between higher NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity troponin T concentrations, and the risk of incident AF in a large cohort of participants with chronic kidney disease. Increased atrial myocardial stretch and myocardial cell injury may be implicated in the high burden of AF in patients with chronic kidney disease