Polypill and Combination Therapy: Blood Pressure and Cardiovascular Risk Reduction.

PURPOSE OF REVIEW: The number of medications prescribed to patients has been progressively increasing, primarily driven by cardioprotective medications. The advent of pharmaceutical 3D printing technology holds the promise of reducing the burden of multiple pills by combining various medications with different release mechanisms into a single tablet. This development encourages a comprehensive review of the evidence supporting the use of combination pills. RECENT FINDINGS: Recent randomized studies have shown higher BP control rates in quadpill groups than in monotherapy groups and improved 6-month BP control rates with a low-dose triple fixed-dose combination (FDC) medication compared to usual care. Recent randomized controlled trials also support FDC use for primary and secondary prevention of cardiovascular disease. Three-dimensional printing technologies such as powder-based (PB) 3D printing, fused deposition modeling (FDM) 3D printing, and semisolid extrusion (EXT) 3D printing are examples of promising technologies that could be utilized to combine multiple medications with different release mechanisms into a single tablet. FDC therapy can provide patients with combination regimens with a reduced pill burden, which promotes improved adherence and efficacy. Recent randomized trials have shown that FDC can be used for primary and secondary prevention of cardiovascular disease with no significant difference in adverse events. Multidisciplinary approaches should be implemented to enhance long-term adherence, and further research on establishing affordable and effective initial dual antihypertensive therapy options is necessary. Pharmaceutical 3D printing technology may play an important role in enhancing the flexibility, affordability, and feasibility of clinical FDC utilization.

Home blood pressure monitoring in CKD.

Hypertension is common in patients with chronic kidney disease (CKD) and the prevalence increases with declining kidney function. Hypertension management is particularly important due to the increased risk of cardiovascular disease and stroke in the CKD population. Most clinical decisions for blood pressure (BP) management are based on BP readings in the office or dialysis unit. These BP readings often are inaccurate. Home BP monitoring provides more data than conventional clinic or dialysis-unit BP measurements and is relatively easy to accomplish, is cost-effective, and has been shown to have an increasing role in the management of BP in the CKD population. This In Practice article focuses on the use of home BP monitoring in patients with CKD. We also provide guidance for choosing a BP monitoring device and review recent literature regarding the use of home BP monitoring and the effect on CKD outcomes. In addition, we address the future use of electronic medical records and how they may interface with home BP monitoring.

Head and Neck Paragangliomas: Overview of Institutional Experience.

Head and neck paragangliomas (HNPGLs) are rare and have high rates of genetic mutations. We conducted a retrospective review of 187 patients with 296 PGLs diagnosed between 1974 and 2023. The mean age of diagnosis was 48.8 years (range 10 to 82) with 69.0% female and 26.5% patients with multiple PGLs. Among 119 patients undergoing genetic testing, 70 (58.8%) patients had mutations, with SDHB (30) and SDHD (26) being the most common. The rates of metastasis and recurrence were higher among patients with SDHB mutations or SDHD mutations associated with multiple PGLs. Metabolic evaluation showed elevated plasma dopamine levels were the most common derangements in HNPGL. MRI and CT were the most common anatomic imaging modalities and DOTATATE was the most common functional scan used in this cohort. Most patients (81.5%) received surgery as the primary definitive treatment, while 22.5% patients received radiation treatment, mostly as an adjuvant therapy or for surgically challenging or inoperable cases. Systemic treatment was rarely used in our cohort. Our single-center experience highlights the need for referral for genetic testing and metabolic evaluation and for a team-based approach to improve the clinical outcomes of patients with HNPGLs.

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.

Ambulatory blood pressure in chronic kidney disease.

Chronic kidney disease (CKD) affects approximately 20 million adults in the United States. Patients with CKD have an increased risk of cardiovascular (CV) disease. Ambulatory blood pressure monitoring (ABPM) provides superior BP measurements when compared to office BP measurements in normotensive, hypertensive and CKD patients. ABPM measurements are often abnormal in CKD, with CKD patients frequently showing an altered circadian rhythm with an increased rate of non-dipping and reverse dipping. The prevalence of non-dippers and reverse-dippers increases progressively as stage of CKD progresses. ABPM has been shown to be a better tool for predicting CV risk, CKD progression, end stage renal disease (ESRD) or death than office-based pressures. ABPM is also additive and adds prognostic value for predicting CKD and CV outcomes when added to estimated glomerular filtration rate (eGFR). Although ABPM is time consuming, it is worth considering, as the data demonstrates that information from ABPM can potentially impact future CV and renal outcomes in patients with CKD.

Pretransplant physical activity predicts all-cause mortality in kidney transplant recipients.

BACKGROUND: Low physical activity (PA) has been associated with higher rates of cardiovascular disease (CVD) and mortality in the general population. Despite the benefits of kidney transplantation, kidney transplant recipients (KTRs) remain at elevated risk for CVD and mortality compared to individuals without kidney disease. METHODS: A prospective cohort of 507 adult KTRs from three academic centers completed the Physical Activity Scale for the Elderly (PASE) at transplantation. PASE scores were divided into tertiles. RESULTS: PA was lower with older age, history of CVD, smoking, and diabetes. During the median 8-year follow-up period, 128 individuals died, among whom 101 had a functioning allograft. In multivariable Cox regression for all-cause mortality, greater PA was strongly associated with better survival (HR: 0.52 for most active vs. inactive tertiles, 95% CI: 0.31-0.87, p = 0.01). Secondary analyses, in which (1) death with a functioning graft was the primary outcome, and (2) PASE scores were converted to the metabolic equivalent of task, revealed similar results. We did not find an association between change of PA after transplantation and mortality. CONCLUSIONS: PA at the time of kidney transplantation is a strong predictor of all-cause mortality and death with graft function. Evaluation of PA level among kidney transplant candidates may be a useful method to risk-stratify patients for survival after kidney transplantation. Kidney transplant candidates and recipients should also be encouraged to be physically active.

Comparative Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Serum Electrolyte Levels in Patients with Type 2 Diabetes: A Pairwise and Network Meta-Analysis of Randomized Controlled Trials.

Background: Previous studies have reported that sodium-glucose co-transporter 2 (SGLT2) inhibitors (SGLT2is) affect levels of serum electrolytes, especially magnesium. This study aimed to integrate direct and indirect trial evidence to maximize statistical power to clarify their overall and comparative effects in patients with type 2 diabetes (T2D). Methods: We systematically searched PubMed, EMBASE, CENTRAL, and ClinicalTrials.gov up to January 2021 to identify eligible randomized controlled trials (RCTs) of SGLT2is that reported mean changes in serum electrolytes, including magnesium, sodium, potassium, phosphate, and calcium. We performed both random-effects pairwise and network meta-analyses to calculate the weighted mean difference (WMD) and 95% confidence intervals (CI). Results: In total, we included 25 RCTs involving 28,269 patients with T2D and 6 SGLT2is. Compared with placebo, SGLT2is were significantly associated with elevations in serum magnesium by 0.07 mmol/L (95% CI, 0.06 to 0.08 mmol/L) and serum phosphate by 0.03 mmol/L (95% CI, 0.02 to 0.04 mmol/L). Our network meta-analysis showed no evidence of significantly superior efficacy of any specific SGLT2 inhibitor over the others, although dapagliflozin was associated with a larger increment in serum magnesium (WMD=0.16 mmol/L) compared with other SGLT2is. Similarly, no statistically detectable differences among the effects of SGLT2is on serum levels of other electrolytes were detected. Conclusions: SGLT2is significantly increased serum magnesium and phosphate levels, consistent with a class effect of SGLT2 inhibition. However, further investigations of long-term efficacy and safety in patients with T2D with different clinical phenotypes are needed.

Is there a role for measuring central aortic pressure?

Peripheral brachial blood pressure measurements by sphygmomanometry remains the standard for measuring and managing blood pressure. Elevated brachial blood pressure is a major risk for cardiovascular disease, and reduction of bracial blood pressure decreases target organ damage and cardiovascular events. However, many patients still succumb to heart disease, stroke, kidney failure, and death even when the brachial blood pressures appear adequately controlled. Central aortic pressure may be more relevant to the pathogenesis of cardiovascular disease, which is not always accurately represented by brachial blood pressure. Noninvasive applanation tonometry can now assess central aortic pressure easily and reliably. Emerging data suggest that central arotic pressure and related parameters are often better and more robust predictors of cardiovascular outcome than peripheral brachial blood pressures.

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.

Health-Related Quality of Life, Depressive Symptoms, and Kidney Transplant Access in Advanced CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Among individuals with chronic kidney disease (CKD), poor self-reported health is associated with adverse outcomes including hospitalization and death. We sought to examine the association between health-related quality-of-life (HRQoL) and depressive symptoms in advanced CKD and subsequent access to the kidney transplant waiting list. STUDY DESIGN: Prospective cohort study. SETTING & POPULATION: 1,676 Chronic Renal Insufficiency Cohort (CRIC) study participants with estimated glomerular filtration rates ≤ 30 mL/min/1.73 m2 at study entry or during follow-up. EXPOSURES: HRQoL ascertained by 5 scales of the Kidney Disease Quality of Life-36 Survey (Physical Component Summary [PCS], Mental Component Summary, Symptoms, Burdens, and Effects), with higher scores indicating better HRQoL, and depressive symptoms ascertained using the Beck Depression Inventory. OUTCOMES: Time to kidney transplant wait-listing and time to pre-emptive wait-listing. ANALYTIC APPROACH: Time-to-event analysis using Cox proportional hazards regression. RESULTS: During a median follow-up of 5.1 years, 652 (39%) participants were wait-listed, of whom 304 were preemptively wait-listed. Adjusted for demographics, comorbid conditions, estimated glomerular filtration rate slope, and cognitive function, participants with the highest scores on the Burden and Effects scales, respectively, had lower rates of wait-listing than those with the lowest scores on the Burden (wait-listing adjusted hazard ratio [aHR], 0.70; 95% CI, 0.57-0.85; P < 0.001) and Effects scales (wait-listing aHR, 0.74; 95% CI, 0.59-0.92; P = 0.007). Participants with fewer depressive symptoms (ie, Beck Depression Inventory score < 14) had lower wait-listing rates than those with more depressive symptoms (aHR, 0.81; 95% CI, 0.66-0.99; P = 0.04). Participants with lower Burden and Effects scale scores and those with higher Symptoms and PCS scores had higher pre-emptive wait-listing rates (aHR in highest tertile of PCS relative to lowest tertile, 1.58; 95% CI, 1.12-2.23; P = 0.01). LIMITATIONS: Unmeasured confounders. CONCLUSIONS: Self-reported health in late-stage CKD may influence the timing of kidney transplantation.

Patterns and Correlates of Baseline Thiazide-Type Diuretic Prescription in the Systolic Blood Pressure Intervention Trial.

Thiazides and thiazide-type diuretics are recommended as first-line agents for the treatment of hypertension, but contemporary information on their use in clinical practice is lacking. We examined patterns and correlates of thiazide prescription in a cross-sectional analysis of baseline data from participants enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT). We examined baseline prescription of thiazides in 7582 participants receiving at least 1 antihypertensive medication by subgroup, and used log-binomial regression to calculate adjusted prevalence ratios for thiazide prescription (versus no thiazide). Forty-three percent of all participants were prescribed a thiazide at baseline, but among participants prescribed a single agent, the proportion was only 16%. The prevalence of thiazide prescription differed significantly by demographic factors, with younger participants, women, and blacks all having higher adjusted prevalence of thiazide prescription than other corresponding subgroups. Participants in the lowest category of kidney function (estimated glomerular filtration rate <30 mL/min per 1.73 m2) were half as likely to be prescribed a thiazide as participants with preserved kidney function. In conclusion, among persons with hypertension and heightened cardiovascular risk, we found that thiazide prescription varied significantly by demographics and kidney disease status, despite limited evidence about relative differences in effectiveness.

Masked Hypertension and Elevated Nighttime Blood Pressure in CKD: Prevalence and Association with Target Organ Damage.

BACKGROUND AND OBJECTIVES: Masked hypertension and elevated nighttime BP are associated with increased risk of hypertensive target organ damage and adverse cardiovascular and renal outcomes in patients with normal kidney function. The significance of masked hypertension for these risks in patients with CKD is less well defined. The objective of this study was to evaluate the association between masked hypertension and kidney function and markers of cardiovascular target organ damage, and to determine whether this relationship was consistent among those with and without elevated nighttime BP. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a cross-sectional study. We performed 24-hour ambulatory BP in 1492 men and women with CKD enrolled in the Chronic Renal Insufficiency Cohort Study. We categorized participants into controlled BP, white-coat, masked, and sustained hypertension on the basis of clinic and 24-hour ambulatory BP. We obtained echocardiograms and measured pulse wave velocity in 1278 and 1394 participants, respectively. RESULTS: The percentages of participants with controlled BP, white-coat, masked, and sustained hypertension were 49.3%, 4.1%, 27.8%, and 18.8%, respectively. Compared with controlled BP, masked hypertension independently associated with low eGFR (-3.2 ml/min per 1.73 m(2); 95% confidence interval, -5.5 to -0.9), higher proteinuria (+0.9 unit higher in log2 urine protein; 95% confidence interval, 0.7 to 1.1), and higher left ventricular mass index (+2.52 g/m(2.7); 95% confidence interval, 0.9 to 4.1), and pulse wave velocity (+0.92 m/s; 95% confidence interval, 0.5 to 1.3). Participants with masked hypertension had lower eGFR only in the presence of elevated nighttime BP (-3.6 ml/min per 1.73 m(2); 95% confidence interval, -6.1 to -1.1; versus -1.4 ml/min per 1.73 m(2); 95% confidence interval, -6.9 to 4.0, among those with nighttime BP <120/70 mmHg; P value for interaction with nighttime systolic BP 0.002). CONCLUSIONS: Masked hypertension is common in patients with CKD and associated with lower eGFR, proteinuria, and cardiovascular target organ damage. In patients with CKD, ambulatory BP characterizes the relationship between BP and target organ damage better than BP measured in the clinic alone.

Renal denervation: a potential new treatment for severe hypertension.

Hypertension is a leading cause of cardiovascular morbidity and mortality. Drug-resistant hypertension remains common despite the availability of several classes of effective antihypertensive agents. Sympathetic hyperactivity has long been recognized as a major contributor to resistant hypertension, but radical sympathectomy was abandoned several decades ago due to its significant side effects. The newly developed, minimally invasive, catheter-based renal sympathetic denervation procedure has been shown in recent trials to produce impressive blood pressure reductions and a favorable safety profile in drug-resistant hypertension. Although the long-term efficacy and safety of renal denervation remains to be determined, emerging data suggest that the benefits of renal denervation may extend beyond blood pressure control.

The single pill triple combination of aliskiren, amlodipine, and hydrochlorothiazide in the treatment of hypertension.

INTRODUCTION: Hypertension is a leading cause of cardiovascular morbidity and mortality, and uncontrolled hypertension remains common despite the availability of several classes of effective antihypertensive medications. Combination therapy with antihypertensive agents of complementary actions has been advocated in the management of hypertension to maximize efficacy and minimize side effects. AREAS COVERED: This review summarizes the current data on the triple combination therapy of aliskiren with amlodipine and hydrochlorothiazide, and discusses the clinical use of single pill triple combination of aliskiren, amlodipine and hydrochlorothiazide in the treatment of hypertension and associated cardiovascular conditions. EXPERT OPINION: Combination therapy with antihypertensive agents of complementary actions is more effective than monotherapy in the management of hypertension. Combining an agent in renin-angiotensin blockade with a dihydropyridine calcium channel blocker (CCB) and a thiazide diuretic has plausibility in maximizing blood pressure reduction and minimizing side effects. The combination of aliskiren with amlodipine and hydrochlorothiazide has shown effective blood pressure lowering and noteworthy tolerability. The single pill triple combination of aliskiren, amlodipine, and hydrochlorothiazide offers five different formulations of escalating dosages of the three agents, allowing dosing flexibility. The decreased pill burden and simplified treatment options with the single pill triple combination provide an opportunity to improve blood pressure control through improved adherence and reduced treatment inertia.

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.

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 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.

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.

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.

Association of metabolic syndrome with development of new-onset diabetes after transplantation.

BACKGROUND: New-onset diabetes after transplantation (NODAT) is a major posttransplant complication associated with lower allograft and recipient survival. Our objective was to determine whether metabolic syndrome pretransplant is independently associated with NODAT development. METHODS: We recruited 640 consecutive incident nondiabetic renal transplant recipients from three academic centers between 1999 and 2004. NODAT was defined as the use of hypoglycemic medication, a random plasma glucose level more than 200 mg/dL, or two fasting glucose levels more than or equal to 126 mg/dL beyond 30 days posttransplant. RESULTS: Metabolic syndrome was common pretransplant (57.2%). NODAT developed in 31.4% of recipients 1 year posttransplant. Participants with metabolic syndrome were more likely to develop NODAT compared with recipients without metabolic syndrome (34.4% vs. 27.4%, P=0.057). Recipients with increasing number of positive metabolic syndrome components were more likely to develop NODAT (metabolic syndrome score prevalence at 1 year: 0 components-0.0%, 1-24.2%, 2-29.3%, 3-31.0%, 4-34.8%, and 5-73.7%, P=0.001). After adjustment for demographics, age by decade (hazard ratio [HR] 1.34 [1.20-1.50], P<0.0001), African American race (HR 1.35 [1.01-1.82], P=0.043), cumulative prednisone dosage (HR 1.18 [1.07-1.30], P=0.001), and metabolic syndrome (HR 1.34 [1.00-1.79], P=0.047) were independent predictors of development of NODAT at 1 year posttransplant. In a multivariable analysis incorporating the individual metabolic syndrome components themselves as covariates, the only pretransplant metabolic syndrome component to remain an independent predictor of NODAT was low high-density lipoprotein (hazard ratio [HR] 1.37 [1.01-1.85], P=0.042). CONCLUSIONS: Metabolic syndrome is an independent predictor for NODAT and is a possible target for intervention to prevent NODAT. Future studies to evaluate whether modification of metabolic syndrome factors pretransplant reduces NODAT development are needed.