Stephanie DeLoach

Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO)

Cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD) is high, and the presence of CKD worsens outcomes of cardiovascular disease (CVD). CKD is associated with specific risk factors. Emerging evidence indicates that the pathology and manifestation of CVD differ in the presence of CKD. During a clinical update conference convened by the Kidney Disease: Improving Global Outcomes (KDIGO), an international group of experts defined the current state of knowledge and the implications for patient care in important topic areas, including coronary artery disease and myocardial infarction, congestive heart failure, cerebrovascular disease, atrial fibrillation, peripheral arterial disease, and sudden cardiac death. Although optimal strategies for prevention, diagnosis, and management of these complications likely should be modified in the presence of CKD, the evidence base for decision making is limited. Trials targeting CVD in patients with CKD have a large potential to improve outcomes.

Vascular Stiffness: Its Measurement and Significance for Epidemiologic and Outcome Studies

Arterial stiffness is recognized increasingly as an important component in the determination of cardiovascular risk, particularly in chronic kidney disease and ESRD populations. Although the technique has been around for nearly 100 yr, in the past 20 to 25 yr, pragmatic noninvasive approaches have allowed the incorporation of arterial stiffness measurements, usually in the form of aortic pulse wave velocity (PWV), into clinical assessment of patients. In populations with high cardiovascular risk, especially those with ESRD, aortic PWV measurements provide predictive utility independent of the standard brachial arterial BP measurements. This review briefly discusses the history of vascular dynamics, the determinants of PWV, and some of the available technologies in current use and concludes with a section on the relevance of arterial stiffness measurements in populations of particular interest to nephrologists.

Aortic calcification predicts cardiovascular events and all-cause mortality in renal transplantation

BACKGROUND Cardiovascular disease is a leading cause of death among renal transplant recipients. Aortic calcification is associated with increased mortality in dialysis subjects. The significance of aortic calcification among renal transplant recipients is unknown. Our objective was to prospectively examine the association of aortic calcification with cardiovascular events and all-cause mortality among asymptomatic incident renal transplant recipients. METHODS One hundred and twelve renal transplant recipients underwent electron beam computed tomography. Aortic calcification was scored by the Agatston method. The mean follow-up time was 5.1 years. Cardiovascular events (heart failure, coronary artery disease, peripheral arterial disease and stroke) and all-cause mortality were recorded. RESULTS The cohort consisted of 62% Caucasians, 38% African Americans and 62% male gender. The mean age was 49.0 +/- 12.5 years. Thirty-four percent had aortic calcification. During follow-up, 12 cardiovascular events and 10 deaths were recorded. Subjects with aortic calcification had more cardiovascular events compared to those without aortic calcification (23.7 versus 4.1%, P = 0.001). Recipients with aortic calcification had higher mortality compared to those without aortic calcification but it did not reach statistical significance (15.8 versus 5.4%, P = 0.07). The univariate hazard ratio of aortic calcification score in a proportional hazard Cox model to assess event-free survival was 1.15 (1.04-1.27, P = 0.01). Diabetes and aortic calcification score were independently associated with survival. In addition to the predictors above, dialysis vintage was an independent predictor for combined future cardiovascular event and mortality. CONCLUSIONS In conclusion, aortic calcification is prevalent among renal transplant recipients and is predictive of future cardiovascular events. Aortic calcification is easily identified by non-invasive testing, and should be considered when assessing cardiovascular risk in asymptomatic renal transplant recipients.

High risk blood pressure and obesity increase the risk for left ventricular hypertrophy in African-American adolescents.

OBJECTIVE To examine the relative effects of high blood pressure (HBP) and obesity on left ventricular mass (LVM) among African-American adolescents; and if metabolic or inflammatory factors contribute to LVM. STUDY DESIGN Using a 2 × 2 design, African-American adolescents were stratified by body mass index percentile (body mass index <95th percentile = non-obese; ≥ 95th percentile = obese) and average blood pressure (BP) (normal BP <120/80 mm Hg; HBP ≥ 120/80). Glucose, insulin, insulin resistance, lipids, and inflammatory cytokines were measured. From echocardiography measures of LVM, calculated LVM index (LVMI) ≥ 95th percentile defined left ventricular hypertrophy (LVH). RESULTS Data included 301 adolescents (48% female), mean age 16.2 years, 51% obese, and 29% HBP. LVMI was highest among adolescents with both obesity and HBP. The multiplicative interaction of obesity and HBP on LVH was not significant (OR = 2.35, P = .20) but the independent additive associations of obesity and HBP with log-odds of LVH were significant; obesity OR = 3.26, P < .001; HBP OR = 2.92, P < .001. Metabolic and inflammatory risk factors were associated with obesity, but had no independent association with LVMI. Compared with those with average systolic BP (SBP) <75th percentile, adolescents with SBP from the 75th percentile to 90th percentile had higher LVMI (33.2 vs 38.7 g/m(2.7), P < .001) and greater LVH (18% vs 43%, P < .001), independent of obesity. CONCLUSIONS Prevalence of LVH is highest among African-American adolescents with average BP ≥ 120/80 mm Hg and obesity. There also is an independent association of LVMI with BP, beginning at the 75th SBP percentile.

Peripheral Artery Disease and CKD: A Focus on Peripheral Artery Disease as a Critical Component of CKD Care

The incidence of peripheral artery disease (PAD) is higher in patients with chronic kidney disease (CKD) than in the general population. PAD is a strong independent risk factor for increased cardiovascular disease mortality and morbidity, including limb amputation, in persons with CKD. Diagnosis of PAD in patients with CKD may be challenging in the absence of classic intermittent claudication or the presence of atypical leg symptoms. In addition, pedal artery incompressibility may decrease the accuracy of ankle-brachial index measurement, the most common PAD diagnostic tool. Alternative methods such as toe-brachial index should be used if clinical suspicion persists despite a normal ankle-brachial index value. Aggressive risk-factor modification, including treatment of diabetes, hyperlipidemia, and hypertension and smoking cessation, should be mandatory in all patients. Treatment of all individuals with PAD should include antiplatelet medications and prescribed supervised exercise programs and/or cilostazol for individuals with claudication symptoms. Preventive foot care measures and a multidisciplinary approach involving podiatrists and vascular and wound care specialists should be used to reduce amputations. Revascularization for critical limb ischemia is associated with poor outcomes in patients with CKD with PAD. Future investigation is recommended to evaluate the benefit of earlier treatment strategies in this high cardiovascular disease risk population with CKD.

Peripheral Arterial Disease: A Guide for Nephrologists

Cardiovascular disease is a major source of morbidity and mortality for patients with chronic kidney disease (CKD). Peripheral arterial disease (PAD) is a strong predictor of coronary artery disease and a risk factor for mortality in the general population. This is of particular interest to nephrologists because the risk for PAD is increased in CKD. Often, PAD is overlooked as a source of morbidity and as a cardiovascular risk factor in this population. This review serves as an overview of the epidemiology, screening, diagnosis, and treatment of PAD with an emphasis on CKD.

Aortic pulse pressure is associated with carotid IMT in chronic kidney disease: report from Chronic Renal Insufficiency Cohort.

BACKGROUND Patients with chronic kidney disease (CKD) have a disproportionate risk of cardiovascular disease. This study was designed to assess the association between two noninvasive measures of cardiovascular risk, pulse wave analysis (PWA), and carotid intima-media thickness (IMT), in a cohort of CKD patients enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. METHODS Three hundred and sixty-seven subjects with CKD enrolled in the CRIC study at the University of Pennsylvania site (mean age 59.9 years, blood pressure 129/74 mm Hg, estimated glomerular filtration rate 48 ml/min/1.73 m2, IMT 0.8 mm) had both carotid IMT and PWA measurements. Carotid ultrasound was also used to determine the presence of plaque. PWA was used to determine augmentation index (AI), amplification ratio (AMPR), aortic pulse pressure (C_PP), and central aortic systolic pressure (C_SP). RESULTS IMT was significantly associated with all PWA-derived measures. However, on multivariable linear regression analysis, only AMPR (regression coefficient -0.072, P = 0.006), C_PP (regression coefficient 0.0025, P < 0.001), and C_SP (regression coefficient 0.0017, P < 0.001) remained significantly associated with IMT. The prevalence of carotid plaque in the cohort was 59%. Of the PWA-derived measures, only C_PP was significantly associated with the presence of carotid plaque (P < 0.001). CONCLUSIONS PWA-derived measures are associated with carotid IMT and plaque in the CKD. Of these measures, C_PP was most associated with carotid IMT and plaque.

Variants in Genes Involved in Functional Pathways Associated with Hypertension in African Americans

Essential hypertension (HBP) is a complex trait with a substantial heritable component. The purpose of this study was to determine if variants in the G‐protein coupled receptor Kinase‐4 (GRK4), nitric oxide synthase‐3 (NOS3), or angiotensin converting enzyme (ACE) genes are associated singly or through complex interactions, with HBP in African Americans aged 18–49 years. TaqMan Assays were used for genotyping the GRK4 and NOS3 variants. The ACE I/D variant was obtained by polymerase chain reaction and electrophoresis. Allelic association tests were performed for the five markers using PLINK. Logistic regression models were fitted to investigate associations between HBP status and the genetic markers. Multilocus analyses were also conducted. The study included 173 hypertensives and 239 normotensives, with stratification into obese and nonobese groups. The GRK4 A486V variant was negatively associated with HBP in the nonobese group (p= 0.048). The TT/CT genotype of GRK4 A486V was associated with decreased risk for HBP relative to the CC genotype after adjusting for age, sex, and body mass index (p= 0.028). Individuals having at least one NOS3 A allele and GRK4 R65L genotype GG had odds of HBP of 2.97 relative to GG homozygotes for NOS3 and GRK4 R65L. These results show very modest effects and do not fully replicate previous studies. Clin Trans Sci 2010; Volume 3: 279–286

Central blood pressures are associated with left ventricular mass index among African-American adolescents.

BACKGROUND There is a high burden of premature cardiovascular disease (CVD) among African Americans. Measures of central aortic blood pressure (CASP) and wave reflection are predictive of CVD risk in adults, but there is a paucity of data regarding the relation of these measures to target organ damage among adolescents. The objective of this study was to examine the relationship between CASP, central pulse pressure (CPP), and augmentation index (AI) with left ventricular mass index (LVMI). METHODS A cohort of 120 African-American adolescents was examined. Study participants underwent measurement of peripheral blood pressure (BP) using auscultation, pulse wave analysis (PWA) for determination of CASP, CPP, and AI, and echocardiography for determination of LVMI. RESULTS The cohort was 55% male, with mean BP 114/62 mm Hg, mean LVMI 36 g/m(2.7), mean CASP 94 mm Hg, mean CPP 31 mmHg, and mean AI was 0.5%. After adjustment for potential confounders, peripheral systolic BP (SBP) was significantly associated with LVMI (P = 0.008), but diastolic pressure was not (P = 0.887). The CASP and CPP were significantly associated with LVMI (P = 0.020 and 0.005, respectively). Peripheral SBP, CASP, and CPP had similar associations with respect to LVMI (r(2) = 0.26, 0. 26, and 0.27, respectively). CONCLUSION Central BP is associated with LVMI among African-American adolescents, and these associations are similar to those seen with peripheral BP measurements.

Aldosterone and aldosterone: renin ratio associations with insulin resistance and blood pressure in African Americans

African Americans have more hypertension and hypertension-related morbidity than whites. Aldosterone, in presence of a high salt intake, contributes to hypertension and tissue injury. Inappropriately elevated aldosterone levels could explain this racial disparity. Our study was conducted to determine if aldosterone is associated with elevated blood pressure (BP) or insulin resistance, independent of obesity. A study was conducted on 483 young adult African Americans without cardiovascular or renal disease. Measurements included anthropometrics, BP, lipids, glucose, insulin, aldosterone, and renin. Urine sodium and potassium estimated sodium intake. The cohort was stratified by tertiles of aldosterone and tertiles of aldosterone/renin ratio (ARR). Average urine sodium/potassium ratio was >3.0 in all groups. Insulin resistance, estimated by homeostasis model, was lowest in the low aldosterone group (geometric mean 1.5 [0.6, 2.2]) compared with the high aldosterone group (1.7 [0.9, 2.7], P < .01). Adjusted analyses detected a significant association of aldosterone with insulin resistance, independent of other variables. BP was significantly higher in the high ARR group compared with low and mid ARR groups (P < .01). The significant association of ARR with BP with high dietary sodium suggests that insufficiently suppressed aldosterone may contribute to BP sensitivity to sodium in African Americans.