Obesity associated inflammation in African American adolescents and adults.

BACKGROUND: C-reactive protein (CRP) is related to adiposity and metabolic risk and predicts events in adults. The objective was to determine if relationships between adiposity and CRP have similar magnitudes in adolescents as adults. METHODS: Healthy African Americans (484 adults and 282 adolescents) were recruited from similar environments. In both cohorts, measurements included anthropometrics, blood pressure (BP), metabolic risk factors and inflammatory markers. After stratification by high-sensitivity CRP (hsCRP: ≤1, 1-≤3, >3 mg/dL), adults and adolescents were compared with regard to body mass index (BMI; kg/m), waist circumference (WC; cm), BP and other risk factors. hsCRP was regressed on BMI and WC with covariates including cohort, age, sex, BP, insulin resistance, smoking, alcohol and other biomarkers. Interaction terms and a subset of the covariates were subject to a supervised variable selection procedure for a final model. Skewed variables were log transformed and summarized by geometric means (GMs) with 1st and 3rd quartiles (Q1, Q3). RESULTS: Among adolescents (16.3%) and adults (34.1%) having high hsCRP(>3 mg/dL), BMI was distributed similarly (GM = 36.4 [32.7, 43.1] and GM = 34.7 [28.8, 40.8], respectively) as was WC (GM = 104.2 [93.0, 119.0] and GM = 104.9 [93.0, 117.2], respectively). In an adjusted regression model, for a given BMI, elevated WC was associated with elevated hsCRP (P = 0.02). Although elevated BMI was significantly associated with elevated hsCRP, the relationship was stronger among adolescents (interaction P = 0.04). CONCLUSIONS: These findings demonstrate that, in African Americans, obesity is associated with inflammation and adverse changes in metabolic parameters among both adolescents and young adults.

Associations of cardiac structure with obesity, blood pressure, inflammation, and insulin resistance in African-American adolescents.

To determine if obesity, blood pressure (BP), markers of inflammation, and insulin resistance are associated with cardiac structure in African-American adolescents, a cross-sectional study was performed on a cohort oversampled for high BP and obesity. Measurements included the following: anthropometrics, BP, homeostasis model assessment (HOMA) to assess insulin resistance, high-sensitivity C-reactive protein, and plasma adipokines (adiponectin, interleukin-6, plasminogen activator inhibitor-1). Echocardiogram measurements were left-ventricular mass index (LVMI) (g/m(2.7)), LV relative wall thickness (LVRWT), left-atrial diameter index [LADI (mm/m)], and LV diastolic time intervals. LADI (r (2) = 0.25) was associated with body mass index (BMI) systolic BP (SBP) and female sex. LVMI (r (2) = 0.35) variation was associated with BMI SBP, heart rate, age, and male sex. LVRWT (r (2) = 0.05) was associated with HOMA. Tissue diastolic intervals were not associated with any risk factor. Inflammatory markers and adipokines were associated with BMI but were not independently associated with any echocardiographic measures. In African-American adolescents, BMI and SBP, but not inflammatory markers or adipokines, are important correlates of LA size and LVM.

Changes in biomarkers associated with living kidney donation.

Living donor kidneys have been associated with better graft and overall survival in kidney transplant recipients. Although a living kidney donation is generally considered safe in carefully selected living donors, concerns of possible adverse effects related to kidney donation remain, especially in younger and high-risk donors. In this study, we examined the changes in a panel of traditional and novel serum biomarkers linked with cardiovascular conditions in a cohort of 34 healthy living kidney donors with a mean age ± SD of 40 ± 10 years and estimated predonation glomerular filtration rate (GFR) of 86 ± 10 ml/min/1.73 m(2). At 6 months after donation, there were no significant changes in the clinical parameters including body mass index and blood pressure despite a significant decline in the mean estimated GFR to 60 ml/min/1.73 m(2). Among the panel of markers, the levels of symmetric dimethylarginine and fibroblast growth factor 23 increased significantly compared to baseline, suggesting that living kidney donation may result in changes in biomarkers that are associated with cardiovascular risk in other cohorts.

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.

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.

Living donor kidney donation: another form of white coat effect.

BACKGROUND/AIMS: Living donor nephrectomy can be associated with increases in blood pressure several years following the procedure, but the best method to assess blood pressure during the living donor evaluation process is unclear. METHODS: Living kidney donors underwent casual clinic and ambulatory blood pressure monitoring (ABPM) and measurement of central aortic pressures at baseline and 6 months following donor nephrectomy. RESULTS: There was a significant decline in clinic systolic blood pressure (SBP; p = 0.001) and central aortic systolic pressure (p = 0.011) during the study period. However, average ABPM was unchanged and other measures of central arterial pressures and Augmentation Index were unchanged at 6 months compared to baseline. CONCLUSIONS: The remarkable differences between clinic SBP and ambulatory SBP prior to donation, and the disappearance of these differences 6 months later, suggest a substantial white coat effect on SBP associated with living kidney donor evaluation. Also, ABPM represents a better way to assess blood pressure prior to kidney donation.

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.

High blood pressure and obesity increase the risk of abnormal glucose tolerance in young adult african americans.

Higher prevalence of both hypertension and obesity in African Americans is associated with a disproportionately greater burden of cardiovascular diseases in this ethnic group. The purpose of this study was to examine whether there is an interaction between hypertension and obesity that significantly increases the expression of metabolic risk factors for cardiovascular disease. Four groups of young adult African Americans were recruited based on their weight and blood pressure (BP). The effects of weight and BP on metabolic risk factors were analyzed based on data obtained from 484 patients. Results demonstrated that high BP and obesity were independently associated with increased odds of abnormal glucose tolerance, 1.8- and 2.2-fold, respectively. The coexistence of both high BP and obesity further increased the odds of abnormal glucose tolerance 4-fold. In addition, the geometric mean of homeostasis model assessment, an estimate of insulin resistance, increased by 18% with high BP, 60% with obesity, and 90% with the presence of both high BP and obesity. Although no statistically significant interaction between high BP and obesity was detected, the relationships of both high BP and obesity with metabolic risk factors were clearly additive.

Relationship of blood pressure and obesity with inflammatory cytokines among African Americans.

OBJECTIVES: Hypertension and obesity are major public health issues. Both conditions are highly prevalent among African Americans and contribute to the increased burden of cardiovascular disease in this group. Inflammation is considered to be an underlying process in both conditions. The authors sought to determine if there is an interaction between high blood pressure (HBP) and obesity that is associated with markedly elevated plasma levels of proinflammatory cytokines in African American adults. METHODS: This study examined 484 African Americans, aged 18-45 years, including people with and without obesity, and also with and without HBP. People known to have diabetes were not enrolled. Plasma levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), plasminogen activator inhibitor 1, tumor necrosis factor alpha (TNF-α), and adiponectin were measured. Participants also underwent an oral glucose tolerance test and measurement of blood pressure and body mass index (BMI). RESULTS: There was no statistically significant interaction between obesity and HBP on plasma levels of adiponectin or the inflammatory cytokines. When both conditions were present, HBP and obesity had additive associations with the expected geometric mean ratios for IL-6 (1.44, 95% CI 1.18 to 1.75), TNF-α (1.31, 95% CI 1.11 to 1.53), hsCRP (2.55, 95% CI 1.99 to 3.26) and negative association with adiponectin (0.61, 95% CI 0.52 to 0.71). Compared with HBP, obesity had the predominant association with cytokine levels. An increase in cytokine plasma levels was detectable when BMI exceeded 25 kg/m2. CONCLUSIONS: Biomarkers of inflammation in African Americans are strongly associated with BMI. A modest additive effect is found with HBP. Interventions to reduce obesity-related inflammation may impact cardiovascular disease outcomes.

Relationship of adipokines with insulin sensitivity in African Americans.

INTRODUCTION: Cytokines produced by adipose tissue, including adiponectin, have been associated with metabolic abnormalities. The purpose of this study was to examine the relationship of insulin sensitivity measured by euglycemic hyperinsulinemic insulin clamp with plasma adiponectin and other adipokines in young adult African Americans. METHODS: Participants were healthy African Americans. Anthropometric measures, blood pressure, an oral glucose tolerance test and an euglycemic hyperinsulinemic insulin clamp were performed. Insulin sensitivity measurements were adjusted for percentage of fat mass. Plasma concentrations of adiponectin, plasminogen activator inhibitor-1 (PAI-1) and interleukin-6 (IL-6) were assayed on plasma from fasting blood samples. Pearson correlation coefficients and multiple regression models were fitted to assess the association between glucose sensitivity and cytokines. RESULTS: In univariate analysis, there were statistically significant correlations of plasma adiponectin level (r = 0.19, P = 0.004), PAI-1 (r = -0.19, P = 0.020) and IL-6 (r = -0.24, P < 0.001) with measures of insulin sensitivity after adjustment for both fat mass and insulin clamp concentration. In multivariate analysis, adiponectin [geometric mean ratios (GMR) 1.15, P = 0.007], PAI-1 (GMR 0.998, P = 0.021) and body mass index (GMR 0.95, P < 0.001) were each independently associated with insulin sensitivity. For IL-6, there was no significant association with insulin sensitivity independent of obesity. CONCLUSION: These data show a significant and independent positive correlation of adiponectin with insulin sensitivity. The relationship of IL-6 with insulin sensitivity seems to be dependent on adiposity.

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.

Endothelin-1 response to glucose and insulin among African Americans.

Endothelin-1 (ET-1) is implicated in the pathogenesis of hypertension. In vitro studies demonstrate that ET-1 is upregulated by insulin and glucose. The purpose of this study was to determine the effects of insulin and glucose on ET-1 levels in young adult African Americans, a population with a high burden of hypertension and diabetes. Plasma and urine ET-1 levels were measured before and after an oral glucose tolerance test (OGTT) and insulin clamp procedure in 288 participants. Subjects were classified according to glucose tolerance and blood pressure (BP) status. Plasma and urine ET-1 were not significantly different among the glucose tolerance groups. There was a trend toward increased plasma ET-1 among those with diabetes compared with impaired glucose tolerance and normal glucose tolerance; however, this was not statistically significant (P = .085). According to BP status, plasma ET-1 was highest among the high BP group compared with the normal BP group (P = .01). After glucose challenge, plasma ET-1 levels decreased and urine ET-1 increased in all three BP groups (P = .037). Our data show that plasma ET-1 is higher among young adult African Americans with hypertension compared with normotension. Urine ET-1 levels increased in response to glucose challenge, possibly indicating early renal injury.

Regulation of transforming growth factor-beta1 by insulin in prediabetic African Americans.

Insulin resistance has been associated with kidney disease even in the absence of diabetes; however, pathways linking insulin resistance to kidney disease are unclear. The purpose of this study was to determine if transforming growth factor (TGF)-beta1, a key cytokine associated with kidney disease, responds to circulating levels of glucose and/or insulin. Urinary TGF-beta1 levels were measured in 249 young adult African Americans (mean age 40) at baseline, after an oral glucose tolerance test and after a euglycemic hyperinsulinemic clamp procedure. Baseline urinary geometric mean TGF-beta1 levels were somewhat lower in those with normal compared with the impaired glucose tolerance. The urinary TGF-beta1 level increased by 56% followed by a 23% decrease in the normal glucose tolerance group, changes that were significant and corresponded to the changes in the plasma glucose and insulin concentrations. The impaired tolerance group showed little change in the urinary TGF-beta1 level following glucose ingestion. All participants had a significant increase in urinary TGF-beta1 level after steady-state hyperinsulinemia, with sustained euglycemia during the clamp procedure in both of the groups. At baseline, there was a significant correlation between the urinary TGF-beta1 level and urinary albumin excretion. Thus our results suggest that insulin contributes to increased TGF-beta1 production and possible early renal injury in prediabetic young African Americans.

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.

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.

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.