Building a pipeline of community-engaged researchers: How interdisciplinary translational research training programs can collaborate with their Community Research Advisory Councils.

Community research advisory councils (C-RAC) bring together community members with interest in research to support design, evaluation, and dissemination of research in the communities they represent. There are few ways for early career researchers, such as TL1 trainees, to develop skills in community-engaged research, and there are limited opportunities for C-RAC members to influence early career researchers. In our novel training collaboration, TL1 trainees presented their research projects to C-RAC members who provided feedback. We present on initial evidence of student learning and summarize lessons learned that TL1 programs and C-RACs can incorporate into future collaborations.

Hemoglobin A1c and C-reactive protein are independently associated with blunted nocturnal blood pressure dipping in obesity-related prediabetes.

Blunted nocturnal dipping in blood pressure (BP) is associated with increased cardiovascular disease (CVD) risk in middle-aged/older adults. The prevalence of blunted nocturnal BP dipping is higher in persons with obesity and diabetes, conditions that are also associated with elevated aortic stiffness and inflammation. Therefore, we hypothesized that elevated glycemia, inflammation and aortic stiffness would be inversely associated with the magnitude of nocturnal systolic BP dipping among middle-aged/older adults with obesity at high CVD risk. Twenty-four hour ambulatory BP monitoring, aortic stiffness (carotid-femoral pulse wave velocity, CF-PWV), hemoglobin A1c (HbA1c) and inflammation (C-reactive protein, CRP) were measured in 86 middle-aged/older adults with obesity and at least one other CVD risk factor (age 40-74 years; 34 male/52 female; body mass index=36.7±0.5 kg m-2; HbA1c=5.7±0.04%). In the entire cohort, CRP (ß=0.40±0.20, P=0.04), but not HbA1c or CF-PWV was independently associated with systolic BP dipping percent (Model R2=0.07, P=0.12). In stratified (that is, presence or absence of prediabetes) multiple linear regression analysis, HbA1c (ß=6.24±2.6, P=0.02) and CRP (ß=0.57±0.2, P=0.01), but not CF-PWV (ß=0.14± 2.6, P=0.74), were independently associated with systolic BP dipping percent (Model R2=0.32, P<0.01) in obese adults with prediabetes but were absent in obese adults without prediabetes (Model R2=0.01 P=0.95). However, nocturnal systolic BP dipping percent (P=0.65), CF-PWV (P=0.68) and CRP (P=0.59) were similar between participants with and without prediabetes. These data suggest that impaired long-term glycemic control and higher inflammation may contribute partly to blunted BP dipping in middle-aged/older adults with obesity-related prediabetes.

Anxiety independently contributes to elevated inflammation in humans with obesity.

OBJECTIVE: Anxious and depressive states are associated with increased cardiovascular disease (CVD) risk and a proinflammatory phenotype, although the latter appears to be at least partially explained by adiposity. It was hypothesized that depression and anxiety would be associated with elevated inflammation independent of adiposity in persons with obesity at high risk of CVD. METHODS: This study explored the relation between baseline anxiety as measured by the Beck Anxiety Inventory and depression as measured by the Beck Depression Inventory-II and baseline serum c-reactive protein (CRP) in a cross-sectional sample of 100 participants [mean (SD) age 57.8 (7.7) years; 64% female] with obesity [mean (SD) body mass index, BMI 37.3 (5.5) kg/m2 ] enrolled in a clinical trial for pharmacological weight loss. RESULTS: Beck Anxiety Inventory, but not Beck Depression Inventory-II, scores were significantly correlated with CRP (ρ = 0.28, P = 0.005). BMI was also highly correlated with CRP (ρ = 0.42, P < 0.0001). In multivariate models, the relation between anxiety and CRP remained significant (P = 0.038), independent of BMI, age, and sex. CONCLUSIONS: Anxiety, but not depression, was associated with elevated inflammation in persons with obesity beyond that attributable to higher BMI. Further study is warranted to assess whether anxiety represents a potential therapeutic target to mitigate corresponding CVD risk associated with elevated inflammation in persons with obesity.

Higher augmentation index is associated with tension-type headache and migraine in middle-aged/older humans with obesity.

OBJECTIVE: Obesity is a major risk factor for chronic daily headaches, including migraine and tension-type headache (TTH). Although migraine is associated with increased risk of cardiovascular diseases (CVD), a relation between TTH and CVD risk has not been established. It was hypothesized that higher carotid-femoral pulse wave velocity (CFPWV) and augmentation index (AI), measures of aortic stiffness and pressure wave reflection, respectively, and biomarkers of CVD risk, would be higher among adults with obesity and migraine or TTH compared with those with no headache. METHODS: Adults with obesity (n = 93; body mass index ≥30 kg/m(2) ) who were between 40 and 75 years old with at least one additional CVD risk factor were enrolled. Subjects had CFPWV and AI assessed and a complete neurological exam for diagnosis of headache in the past 12 months. RESULTS: Adults with obesity and TTH (P = 0.018), but not migraine (P = 0.29), had significantly higher AI compared with those with no headache. When both CFPWV and AI were considered in a logistic regression model with migraine or TTH, only AI was associated with TTH (P = 0.008) and migraine (P = 0.032) but could not distinguish between the two headache phenotypes. CONCLUSIONS: Increased aortic AI but not stiffness is associated with TTH and migraine among middle-aged/older adults with obesity and high CVD risk.

Systemic exposure to aminoglycosides following knee and hip arthroplasty with aminoglycoside-loaded bone cement implants.

BACKGROUND: Aminoglycoside-loaded bone cement (ALBC) implants are frequently used in orthopedic surgery. Parenteral aminoglycosides are known to cause nephrotoxicity. Reports of acute renal failure in patients receiving ALBC implants have been reported in the literature and at our hospital. OBJECTIVE: To evaluate, as part of a performance improvement project, whether patients undergoing arthroplasty procedures have detectable aminoglycoside serum concentrations following ALBC implantation and to evaluate corresponding changes in serum creatinine. METHODS: Patients undergoing hip or knee revision or resection who received an ALBC implant between January and April 2010 were included in our evaluation. In addition to baseline demographic information, we measured aminoglycoside concentrations and serum creatinine levels during the early postoperative period, prior to hospital discharge, and at the follow-up clinic visit when possible. RESULTS: Seventeen patients were evaluated: 13 women and 4 men with a mean age of 69 years (range 50-84). Eight patients had a preoperative diagnosis of infection and received high-dose ALBC implants as treatment and 9 patients received lower-dose ALBC implants for infection prophylaxis. Eight patients had detectable aminoglycoside serum concentrations (mean 0.42 µg/mL; range 0.3 to 2.0); 1 patient had an aminoglycoside serum concentration of 0.9 µg/mL on postoperative day 38. Patients who did not have a detectable aminoglycoside serum concentration on the first postoperative day did not have a detectable concentration in the following serum samples. Six patients had elevation of serum creatinine by greater than 0.3 mg/dL from baseline. CONCLUSIONS: The number of patients in this study is small; however, this report raises a potential concern for the safety of high-dose ALBC implants. We recommend measuring aminoglycoside serum concentrations in the early postoperative period to identify patients in need of further monitoring. Further studies are needed to determine risk factors for systemic toxicity.

Sympathetic nervous system in obesity-related hypertension: mechanisms and clinical implications.

Obesity markedly increases the risk of hypertension and cardiovascular disease, which may be related to activation of the sympathetic nervous system (SNS). Sympathetic overactivity directly and indirectly contributes to blood pressure (BP) elevation in obesity, including stimulation of the renin-angiotensin-aldosterone system (RAAS). The adipocyte-derived peptide leptin suppresses appetite, increases thermogenesis, but also raises SNS activity and BP. Obese individuals exhibit hyperleptinemia but are resistant to its appetite-suppressing actions. Interestingly, animal models of obesity exhibit preserved sympathoexcitatory and pressor actions of leptin, despite resistance to its anorexic and metabolic actions, suggesting selective leptin resistance. Disturbance of intracellular signaling at specific hypothalamic neural networks appears to underlie selective leptin resistance. Delineation of these pathways should lead to novel approaches to treatment. In the meantime, treatment of obesity-hypertension has relied on antihypertensive drugs. Although sympathetic blockade is mechanistically attractive in obesity-hypertension, in practice its effects are disappointing because of adverse metabolic effects and inferior outcomes. On the basis of subgroup analyses of obese patients in large randomized clinical trials, drugs such as diuretics and RAAS blockers appear superior in preventing cardiovascular events in obesity--hypertension. An underused alternative approach to obesity-hypertension is induction of weight loss, which reduces circulating leptin and insulin, partially reverses resistance to these hormones, decreases sympathetic activation and improves BP and other risk factors. Though weight loss induced by lifestyle is often modest and transient, carefully selected pharmacological weight loss therapies can produce substantial and sustained antihypertensive effects additive to lifestyle interventions.