The utility of home blood pressure load in predicting average self-measured blood pressure.

OBJECTIVES: Average values for self-measured blood pressure (SMBP) more accurately reflect a patient's risk of cardiovascular disease than do office measurements. Oftentimes, however, patients provide lists of individual home blood pressure (BP) measurements, and average values cannot be computed within the time constraints of a clinic visit. In contrast, the home BP load - defined as the proportion of BP values greater than a partition value (e.g., 130 mmHg) - can be easily calculated. We examined the utility of the BP load in predicting the mean SMBP and confirming elevated SMBP. METHODS: Four hundred twenty untreated adults at least 30 years of age acquired SMBP data twice in the morning and twice in the evening over 10 days. The 'true' SMBP was defined as the mean of these 40 determinations. RESULTS: Using all 10 days of BP data and a systolic BP threshold of 130 mmHg, the average SMBP associated with a home BP load of 0.50 was 130 mmHg, with a 95% prediction interval of 126-133 mmHg. True systolic SMBP was approximately 6 mmHg lower and higher at home BP loads of 0.25 and 0.75, respectively. There was a 90% probability that the true systolic SMBP was greater than 130 mmHg if the systolic home BP load was at least 0.60. Corresponding values for 3 days and 1 day of SMBP were at least 0.68 and at least 0.84, respectively. CONCLUSION: Our analysis demonstrates that the home BP load can be used to estimate the average BP acquired on home monitoring and confirm elevated SMBP.

Depressive symptoms are associated with clinical outcomes in heart failure with reduced ejection fraction.

AIMS: The objective of this study was to examine associations between elevated depressive symptoms and increased risk of adverse clinical events patients with heart failure and reduced ejection fraction (HFrEF), as well as the potential contribution of health behaviours. METHODS AND RESULTS: One hundred forty-two men and women with HFrEF were enrolled through heart failure (HF) clinics and followed over time. At baseline and 6 months, depressive symptoms were assessed by the Beck Depression Inventory-II (BDI-II) and HFrEF disease activity by B-type natriuretic peptide (BNP). The Self-Care of Heart Failure Index (SCHFI) was used to assess HF self-care behaviours. Proportional hazards regression models assessed the contribution of depressive symptoms and HFrEF disease biomarkers on death or cardiovascular hospitalization. Over a median follow-up period of 4 years, 42 patients (30%) died, and 84 (60%) had cardiovascular hospitalizations. A 10-point higher baseline BDI-II score was associated with a 35% greater risk of death or cardiovascular hospitalization. Higher baseline BDI-II scores were associated with poorer HF self-care maintenance behaviours (R = -0.30, P < 0.001) and fewer daily steps (R = -0.19, P = 0.04), suggesting that elevated depressive symptoms may diminish important health behaviours. Increases in plasma BNP over 6 months were associated with worse outcomes. Changes in BDI-II and plasma BNP over 6 months were positively related (R = 0.25, P = 0.004). CONCLUSIONS: This study confirms that elevated depressive symptoms are associated with an increased likelihood of adverse clinical outcomes in patients with HFrEF. Poor health behaviours may contribute to the adverse association of elevated depressive symptoms with the increased hazard of adverse clinical outcomes.

Inhaled endotoxin induces a systemic neutrophil response without affecting cardiovascular measures in a randomized cross-over exposure study.

OBJECTIVE: The gram-negative bacterial cell wall component endotoxin (lipopolysaccharide, LPS) is a key component of particulate matter (PM). PM exposure is associated with cardiovascular morbidity and mortality. However, the contribution of individual components of PM to acute and chronic cardiovascular measures is not clear. This study examines whether systemic inflammation induced by LPS inhalation causes acute changes in cardiovascular physiology measures. MATERIALS AND METHODS: In this double blinded, placebo-controlled crossover study, fifteen adult volunteers underwent inhalation exposure to 20,000 EU Clinical Center Reference Endotoxin (CCRE). Peripheral blood and induced sputum neutrophils were obtained at baseline and six hours post-exposure. Blood pressure, measures of left ventricular function (ejection fraction (LVEF) and global longitudinal strain (LVGLS)), and indices of endothelial function (flow mediated dilation (FMD) and velocity time integral during hyperemia (VTIhyp)) were measured before and after treatment. Wilcoxon sign-rank tests and linear mixed models were used for statistical analysis. RESULTS: In comparison with normal saline, LPS inhalation resulted in significant increases in peripheral blood and sputum neutrophils but was not associated with significant alterations in blood pressure, LVGLS, LVEF, FMD, or VTIhyp. DISCUSSION AND CONCLUSIONS: In healthy adults, systemic inflammation after LPS inhalation was not associated with acute changes in cardiovascular physiology. Larger studies are needed to investigate the effects of other PM components on inflammation induced cardiovascular dysfunction.

Association of Depression Symptoms and Biomarkers of Risk on Clinical Outcomes in HFrEF.

BACKGROUND: Prior studies have demonstrated an association of depression with adverse clinical outcomes in patients with HFrEF, but the possible mechanisms responsible for the association are not unserstood. METHODS: 142 men and women with HFrEF were enrolled through HF clinics and followed over time. At baseline and 6-months, depression was assessed by the Beck Depression Inventory (BDI-II) and disease activity by B-type natriuretic peptide (BNP). Proportional Hazards Regression Models assessed the contribution of depressive symptoms and HFrEF disease biomarkers on death or cardiovascular hospitalization. RESULTS: Over a median follow-up period of 4 years, 42 patients (30%) died, and 84 (60%) had cardiovascular hospitalizations. A 10-point higher baseline BDI-II score was associated with a 35% higher hazard of death or cardiovascular hospitalization. Greater baseline BDI-II scores were associated with poorer HF self-care maintenance (R=-0.30, p<0.001) and fewer daily steps (R=-0.19, p=0.04), suggesting that depression may adversely affect important health behaviors. Increases in plasma BNP over 6 months were associated with worse outcomes. Changes in BDI-II score and plasma BNP over 6 months were positively correlated (R=0.25, p=0.004). CONCLUSIONS: This study underscores the importance of elevated depression symptoms and their association with an increased likelihood of adverse clinical outcomes in patients with HFrEF. Health behaviors may play a greater role than direct biobehavioral pathways in the adverse effects of depression on the HF disease trajectory and resultant clinical outcomes.

Cardiology and lifestyle medicine.

Poor lifestyle habits, such as physical inactivity and poor diets, are highly prevalent within society and even more so among patients with chronic disease. The need to stem poor lifestyle habits has led to the development of a new field of Lifestyle Medicine, whose mission is to prevent, treat, and even reverse chronic diseases through lifestyle interventions. Three fields within Cardiology relate to this mission: Cardiac Rehabilitation, Preventive Cardiology, and Behavioral Cardiology. Each of these three fields have contributed substantially to the reduction of cardiovascular disease (CVD) morbidity and mortality. The historic contributions of these three cardiac fields are reviewed as well as the challenges each of these fields has faced in optimizing the application of lifestyle medicine practices. A shared agenda between Cardiology and the American College of Lifestyle Medicine could further the utilization of behavioral interventions. This review suggests seven steps that could be shared by these organizations and other medical societies. First, there is a need to develop and promulgate the assessment of lifestyle factors as "vital signs" during patient visits. Second, developing a strong partnership between the fields of Cardiology and Physiatry could improve important aspects of cardiac care, including a potential redesign of cardiac stress testing. Third, behavioral evaluations should be optimized at patients' entrée points into medical care since these may be considered "windows of opportunity". Fourth, there is a need to broaden cardiac rehabilitation into inexpensive programs and make this program eligible for patients with risk factors but no known CVD. Fifth, lifestyle medicine education should be integrated into the core competencies for relevant specialties. Sixth, there is a need for inter-societal advocacy to promote lifestyle medicine practices. Seventh, the well-being effects of healthy lifestyle behaviors, such as their impact on one's sense of vitality, should be emphasized.

Lifestyle modification and cognitive function among individuals with resistant hypertension: cognitive outcomes from the TRIUMPH trial.

BACKGROUND: Resistant hypertension is associated with increased risk of cognitive decline, stroke, and dementia. Lifestyle modification has been suggested to improve cognitive function through its salutary effects on vascular function. METHODS: Participants included 140 patients with resistant hypertension participating in the TRIUMPH trial. Participants were randomized to a cardiac rehabilitation-based lifestyle program (C-LIFE) or a standardized education and physician advice condition (SEPA). Participants completed a 45-min cognitive test battery consisting of tests of Executive Functioning and Learning, Memory, and Processing Speed. Biomarkers of vascular [flow mediated dilation of the brachial artery (FMD)], microvascular, and cerebrovascular function were also collected, in addition to weight, fitness, and ambulatory blood pressure. RESULTS: Participants averaged 63 years of age, 48% women, 59% black, and obese [mean BMI = 36 kg/m 2 (SD = 4)]. Cognitive performance improved across the entire cohort during the 4-month trial [ t -scores pretreatment = 48.9 (48, 50) vs. posttreatment = 50.0 (49, 51), P  < 0.001]. Postintervention Executive Function/Learning composite performance was higher for participants in C-LIFE compared to SEPA ( d  = 0.37, P  = 0.039). C-LIFE intervention effects on Memory and Processing Speed were moderated by sex and baseline stroke risk, respectively ( P  = 0.026 and P  = 0.043 for interactions), such that males and participants with greater stroke risk showed the greatest cognitive changes. FMD [C-LIFE: +0.3% (-0.3, 1.0) vs. SEPA: -1.4% (-2.5, -0.3), P  = 0.022], and microvascular function [C-LIFE: 97 (65, 130) vs. SEPA: 025 (-75, 23), P  < 0.001] were improved in C-LIFE compared with SEPA, whereas cerebrovascular reactivity was not [C-LIFE: -0.2 (-0.4, 0) vs. SEPA: 0.1 (-0.2, 0.4), P  = 0.197). Mediation analyses suggested that increased executive function/learning was associated with reduced ambulatory SBP levels secondary to weight loss [indirect effect: B  = 0.25 (0.03, 0.71)]. CONCLUSION: Lifestyle modification individuals with resistant hypertension improves cognition, which appeared to be associated with reduced ambulatory SBP changes through weight loss. Cognitive improvements were accompanied by parallel improvements in endothelial and microvascular function.

Cerebrovascular Function, Vascular Risk, and Lifestyle Patterns in Resistant Hypertension.

BACKGROUND: Impaired cerebrovascular reactivity (CVR) and blunted cerebral hemodynamic recruitment are thought to be important mechanisms linking hypertension to cerebrovascular and cognitive outcomes. Few studies have examined cardiovascular or dietary correlates of CVR among hypertensives. OBJECTIVE: To delineate associations between cardiometabolic risk, diet, and cerebrovascular functioning among individuals with resistant hypertension from the TRIUMPH trial (n = 140). METHODS: CVR was assessed by examining changes in tissue oxygenation (tissue oxygenation index [TOI] and oxygenated hemoglobin [HBO2]) using functional near-infrared spectroscopy (fNIRS) during a breath holding test, a standardized CVR assessment to elicit a hypercapnic response. Participants also underwent fNIRS during three cognitive challenge tasks. Vascular function was assessed by measurement of brachial artery flow-mediated dilation and hyperemic flow response. Cardiometabolic fitness was assessed from peak VO2 on an exercise treadmill test and body mass index. Dietary patterns were quantified using the DASH eating score. Cognitive function was assessed using a 45-minute test battery assessing Executive Function, Processing Speed, and Memory. RESULTS: Greater levels fitness (B = 0.30, p = 0.011), DASH compliance (B = 0.19, p = 0.045), and lower obesity (B = -0.30, p = 0.004), associated with greater changes in TOI, whereas greater flow-mediated dilation (B = 0.19, p = 0.031) and lower stroke risk (B = -0.19, p = 0.049) associated with greater HBO2. Similar associations were found for cerebral hemodynamic recruitment, and associations between CVR and cognition were moderated by duration of hypertension. CONCLUSION: Impaired CVR elevated cardiometabolic risk, obesity, vascular function, and fitness among hypertensives.

Hypertension-mediated organ damage in masked hypertension.

OBJECTIVES: Masked hypertension - a blood pressure (BP) phenotype characterized by a clinic BP in the normal range but elevated BP outside the office - is associated with early hypertension-mediated organ damage. This study examined early target organ manifestations of masked hypertension diagnosed by home (HBPM) and ambulatory (ABPM) BP monitoring. METHODS: Left ventricular (LV) structure and diastolic function measured by echocardiography, microalbuminuria, and coronary artery calcification were evaluated in 420 patients with high clinic BP (SBP 120-150 mmHg or DBP 80-95 mmHg). Evidence of hypertension-mediated organ damage was compared in patients with sustained normotension, masked hypertension, and sustained hypertension based on measurements by HBPM, daytime ABPM, and 24-h ABPM. RESULTS: The 420 participants averaged 48 (12) [mean (SD)] years of age; the average clinic BP was 130 (13)/81 (8) mmHg. In individuals with masked hypertension diagnosed by HBPM, indexed LV mass, relative wall thickness, and e' and E/e' (indices of LV relaxation), were generally intermediate between values observed in normotensives and sustained hypertensive patients, and were significantly greater in masked hypertension than normotensives. Similar trends were observed when masked hypertension was diagnosed by ABPM but a diagnosis of masked hypertension was not as reliably associated with LV remodeling or impaired LV relaxation in comparison to normotensives. There were trends towards greater likelihoods of detectable urinary microalbumin and coronary calcification in masked hypertension than in normotensives. CONCLUSION: These results support previous studies demonstrating early hypertension-mediated organ damage in patients with masked hypertension, and suggest that HBPM may be superior to ABPM in identifying patients with masked hypertension who have early LV remodeling and diastolic LV dysfunction.

Effects of Lifestyle Modification on Patients With Resistant Hypertension: Results of the TRIUMPH Randomized Clinical Trial.

BACKGROUND: Although lifestyle modifications generally are effective in lowering blood pressure (BP) among patients with unmedicated hypertension and in those treated with 1 or 2 antihypertensive agents, the value of exercise and diet for lowering BP in patients with resistant hypertension is unknown. METHODS: One hundred forty patients with resistant hypertension (mean age, 63 years; 48% female; 59% Black; 31% with diabetes; 21% with chronic kidney disease) were randomly assigned to a 4-month program of lifestyle modification (C-LIFE [Center-Based Lifestyle Intervention]) including dietary counseling, behavioral weight management, and exercise, or a single counseling session providing SEPA (Standardized Education and Physician Advice). The primary end point was clinic systolic BP; secondary end points included 24-hour ambulatory BP and select cardiovascular disease biomarkers including baroreflex sensitivity to quantify the influence of the baroreflex on heart rate, high-frequency heart rate variability to assess vagally mediated modulation of heart rate, flow-mediated dilation to evaluate endothelial function, pulse wave velocity to assess arterial stiffness, and left ventricular mass to characterize left ventricular structure. RESULTS: Between-group comparisons revealed that the reduction in clinic systolic BP was greater in C-LIFE (-12.5 [95% CI, -14.9 to -10.2] mm Hg) compared with SEPA(-7.1 [-95% CI, 10.4 to -3.7] mm Hg) (P=0.005); 24-hour ambulatory systolic BP also was reduced in C-LIFE (-7.0 [95% CI, -8.5 to -4.0] mm Hg), with no change in SEPA (-0.3 [95% CI, -4.0 to 3.4] mm Hg) (P=0.001). Compared with SEPA, C-LIFE resulted in greater improvements in resting baroreflex sensitivity (2.3 ms/mm Hg [95% CI, 1.3 to 3.3] versus -1.1 ms/mm Hg [95% CI, -2.5 to 0.3]; P<0.001), high-frequency heart rate variability (0.4 ln ms2 [95% CI, 0.2 to 0.6] versus -0.2 ln ms2 [95% CI, -0.5 to 0.1]; P<0.001), and flow-mediated dilation (0.3% [95% CI, -0.3 to 1.0] versus -1.4% [95% CI, -2.5 to -0.3]; P=0.022). There were no between-group differences in pulse wave velocity (P=0.958) or left ventricular mass (P=0.596). CONCLUSIONS: Diet and exercise can lower BP in patients with resistant hypertension. A 4-month structured program of diet and exercise as adjunctive therapy delivered in a cardiac rehabilitation setting results in significant reductions in clinic and ambulatory BP and improvement in selected cardiovascular disease biomarkers. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02342808.

Lifestyle Interventions Reduce the Need for Guideline-Directed Antihypertensive Medication.

BACKGROUND: The 2017 ACC-AHA Hypertension Guideline recommends initiation of antihypertensive drug therapy based on blood pressure (BP) and an assessment of global cardiovascular disease (CVD) risk, but intensive lifestyle modification may lower BP to below recommended thresholds for treatment in some patients. METHODS: We examined the effects of lifestyle modification on calculated CVD risk and on the indications for BP-lowering medications in individuals with untreated hypertension. Participants included 144 adults with BP 130-160/80-99 mm Hg who were randomized to 16 weeks of DASH (Dietary Approaches to Stop Hypertension) diet plus behavioral weight management (DASH + WM), DASH diet alone (DASH), or Usual Care. RESULTS: The mean age of the study cohort was 52.0 years; the average baseline BP was 138 ± 9/86 ± 6 mm Hg. The 10-year CVD risk, as calculated by the Pooled Cohort Equations, was 5.7%. The adjusted 10-year risk fell to 4.4% in the DASH + WM group and to 5.0% in the DASH arm, but was not significantly changed (5.7%) in the Usual Care controls. The percentages of participants with guideline-based indications for antihypertensive drugs fell from 51% to 18% in the DASH + WM group and from 48% to 22% in the DASH group; and did not change significantly (49% to 44%) in the Usual Care group (P = 0.010 for the active intervention groups vs. Usual Care; P = 0.042 for DASH + WM vs. DASH). CONCLUSIONS: These data demonstrate that in men and women with mildly elevated BP, lifestyle interventions can lower the calculated CVD risk and dramatically decrease the number of individuals for whom guideline-directed antihypertensive medication is indicated.

Perimenopausal transdermal estradiol replacement reduces serum HDL cholesterol efflux capacity but improves cardiovascular risk factors.

BACKGROUND: The cardiovascular (CV) safety of estrogen replacement therapy (ERT) in perimenopausal women remains uncertain. Although exogenous estrogens increase HDL cholesterol (HDL-C), estrogen-mediated effects on alternative metrics of HDL that may better predict CV risk are unknown. OBJECTIVE: To determine the effects of transdermal ERT on HDL composition and cholesterol efflux capacity (CEC), as well as the relationships between these metrics and CV risk factors. METHODS: Fasting plasma samples were analyzed from 101 healthy, perimenopausal women randomized to receive either transdermal placebo or transdermal estradiol (100 µg/24 h) with intermittent micronized progesterone. At baseline and after 6 months of treatment, serum HDL CEC, HDL particle concentration, HDL protein composition, insulin resistance and brachial artery flow-mediated dilatation (FMD) were measured. RESULTS: No difference between groups was found for change in plasma HDL-C (p = 0.69). Between-group differences were found for changes in serum HDL total CEC [median change from baseline -5.4 (-17.3,+8.4)% ERT group versus +5.8 (-6.3,+16.9)% placebo group, p = 0.01] and ABCA1-specific CEC [median change from baseline -5.3 (-10.7,+6.7)% ERT group versus +7.4 (-1.5,+18.1)% placebo group, p = 0.0002]. Relative to placebo, transdermal ERT led to reductions in LDL-C (p < 0.0001) and insulin resistance (p = 0.0002). An inverse correlation was found between changes in serum HDL total CEC and FMD (ß = -0.26, p = 0.004). CONCLUSIONS: Natural menopause leads to an increase in serum HDL CEC, an effect that is abrogated by transdermal ERT. However, transdermal ERT leads to favorable changes in major CV risk factors.

Actigraphy-Derived Sleep Efficiency Is Associated With Endothelial Function in Men and Women With Untreated Hypertension.

BACKGROUND: Poor sleep quality is increasingly recognized as an important and potentially modifiable risk factor for cardiovascular disease (CVD). Impaired endothelial function may be 1 mechanism underlying the association between poor sleep and CVD risk. The present study examined the relationship between objective measures of sleep quality and endothelial function in a sample of untreated hypertensive adults. METHODS: Participants were 127 men (N = 74) and women (N = 53), including 55 African Americans and 72 White Americans, aged 40-60 years (mean age, 45.3 ± 8.5 years), with untreated hypertension (systolic blood pressure 130-159 mm Hg and/or diastolic blood pressure 85-99 mm Hg). Noninvasive brachial artery flow-mediated dilation (FMD) was assessed by ultrasound. Sleep parameters, including sleep efficiency (SE), total sleep time (TST), and subjective sleep quality, were assessed over 7 consecutive days by wrist actigraphy. RESULTS: Participants averaged 7.76 ± 1 hours in bed, with an average SE of 78 ± 9%, and TST of 6 ± 1 hours. Brachial FMD averaged 3.5 ± 3.1%. In multivariate analyses controlling for sex, race, body mass index, clinic blood pressure, income, smoking, alcohol use, and baseline arterial diameter, SE was positively associated with FMD (ß = 0.28, P = 0.012). Subjective sleep quality (ß = -0.04, P = 0.63) and TST (ß = -0.11, P = 0.25) were unrelated to FMD. CONCLUSIONS: Poor sleep as indicated by low SE was associated with impaired FMD. These findings for SE are consistent with previous observations of other measures implicating poor sleep as a CVD risk factor. Interventions that improve sleep may also help lower CVD risk.

Effect of ultrafiltration profiling on outcomes among maintenance hemodialysis patients: a pilot randomized crossover trial.

BACKGROUND: More rapid fluid removal during hemodialysis is associated with adverse cardiovascular outcomes and longer dialysis recovery times. The effect of ultrafiltration (UF) profiling, independent of concomitant sodium profiling, on markers of intradialytic hemodynamics and other outcomes has been inadequately studied. METHODS: Four-phase, blinded crossover trial. Participants (UF rates > 10 mL/h/kg) were assigned in random order to receive hemodialysis with UF profiling (constantly declining UF rate, intervention) vs. hemodialysis with conventional UF (control). Each 3-week 9-treatment period was followed by a 1-week 3-treatment washout period. Participants crossed into each study arm twice (2 phases/arm); 18 treatments per treatment type. The primary outcomes were intradialytic hypotension, pre- to post-dialysis troponin T change, and change from baseline in left ventricular global longitudinal strain. Other outcomes included intradialytic symptoms and blood volume measured-plasma refill (post-dialysis volume status measure), among others. Each participant served as their own control. RESULTS: On average, the 34 randomized patients (mean age 56 years, 24% female, mean dialysis vintage 6.3 years) had UF rates > 10 mL/h/kg in 56% of treatments during the screening period. All but 2 patients completed the 15-week study (prolonged hospitalization, kidney transplant). There was no significant difference in intradialytic hypotension, troponin T change, or left ventricular strain between hemodialysis with UF profiling and conventional UF. With UF profiling, participants had significantly lower odds of light-headedness and plasma refill compared to hemodialysis with conventional UF. CONCLUSIONS: Ultrafiltration (UF) profiling did not reduce the odds of treatment-related cardiac stress but did reduce the odds of light-headedness and post-dialysis hypervolemia. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03301740 (registered October 4, 2017).

Metabolic and Neurocognitive Changes Following Lifestyle Modification: Examination of Biomarkers from the ENLIGHTEN Randomized Clinical Trial.

BACKGROUND: Previous studies have demonstrated that aerobic exercise (AE) and the Dietary Approaches to Stop Hypertension (DASH) diet can improve neurocognition. However, the mechanisms by which lifestyle improves neurocognition have not been widely studied. We examined the associations between changes in metabolic, neurotrophic, and inflammatory biomarkers with executive functioning among participants from the Exercise and Nutritional Interventions for Neurocognitive Health Enhancement (ENLIGHTEN) trial. OBJECTIVE: To examine the association between changes in metabolic function and neurocognition among older adults with cognitive impairment, but without dementia (CIND) participating in a comprehensive lifestyle intervention. METHODS: ENLIGHTEN participants were randomized using a 2×2 factorial design to receive AE, DASH, both AE+DASH, or a health education control condition (HE) for six months. Metabolic biomarkers included insulin resistance (homeostatic model assessment [HOMA-IR]), leptin, and insulin-like growth factor (IGF-1); neurotrophic biomarkers included brain derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF); and inflammatory biomarkers included interleukin-6 (IL-6) and C-Reactive Protein (CRP). RESULTS: Participants included 132 sedentary older adults (mean age = 65 [SD = 7]) with CIND. Results demonstrated that both AE (d = 0.48, p = 0.015) and DASH improved metabolic function (d = 0.37, p = 0.039), without comparable improvements in neurotrophic or inflammatory biomarkers. Greater improvements in metabolic function, including reduced HOMA-IR (B = -2.3 [-4.3, -0.2], p = 0.033) and increased IGF-1 (B = 3.4 [1.2, 5.7], p = 0.004), associated with increases in Executive Function. CONCLUSION: Changes in neurocognition after lifestyle modification are associated with improved metabolic function.

IL-6 Response to Psychosocial Stress Predicts 12-month Changes in Cardiometabolic Biomarkers in Perimenopausal Women.

OBJECTIVE: Cardiometabolic diseases are the number one cause of mortality, accounting for over one third of all deaths in the United States. Cardiometabolic risk further increases with psychosocial stress exposure and during menopausal transition in women. Because disease risk and stress burden are associated with aberrant immune signaling, we hypothesized that responses of interleukin-6 (IL-6) to psychosocial stress may predict longitudinal cardiometabolic outcomes in perimenopausal women. METHODS: We conducted post hoc analyses in 151 perimenopausal or early postmenopausal women participants in a previously completed study. At study onset, participants underwent the Trier Social Stress Test (TSST), and plasma IL-6 was measured repeatedly before and during the 1 hour post-TSST. Subsequently, participants were randomly assigned to either hormonal treatment (HT) or placebo and followed for 12 months to determine longitudinal changes in cardiometabolic biomarkers. RESULTS: Greater IL-6 reactivity to stress, measured with baseline-adjusted area under the curve, predicted 12-month decrease in flow-mediated dilatation of the brachial artery (P = 0.0005), a measure of endothelial-dependent vascular function, but not in endothelial-independent function measured with nitroglycerin-mediated dilatation (P = 0.17). Greater baseline IL-6 levels predicted 12-month increase in insulin resistance based on the homeostatic model assessment of insulin resistance score (P = 0.0045) and in the number of criteria met for metabolic syndrome (P = 0.0008). These predictions were not moderated by HT. CONCLUSIONS: Greater baseline IL-6 levels as well as its reactivity to stress may predict worsening in distinct cardiometabolic biomarkers as women transition to menopause. Interleukin-6 reactivity predicts decline in endothelial-dependent vascular function, whereas baseline IL-6 presages accumulation of metabolic risk.

Progression in the severity of aortic stenosis according to race among those with advanced chronic kidney disease.

BACKGROUND: There is a higher prevalence of aortic stenosis (AS) in patients with advanced chronic kidney disease (CKD) and European ancestry. However, studies comparing AS progression in white and black patients in an advanced CKD population do not exist. METHODS: Advanced CKD (stage IV-V) patients who were referred to the UNC Cardiorenal Clinic for pre-operative kidney transplant evaluation, and diagnosed with either AS (mild, moderate, or severe) or a left ventricular outflow tract velocity ≥2 m/s at any point between 2006-2016 were eligible for inclusion. Serial transthoracic echocardiograms over the 10-year period determined AS progression. All echocardiograms acquired after renal transplantation or aortic valve replacement were excluded. The rates of change of three indices of AS severity [mean gradient, aortic valve area (AVA), and aortic valve velocity] were compared between white and black patients. Mixed effects linear models with repeated measures were used to estimate the overall and race-stratified yearly rate of progression for each index, adjusted for age, sex, smoking status, dialysis, and baseline cholesterol. RESULTS: Of 1,283 patients, 140 (34% white, 66% black) developed or had baseline AS. Initially, 81% had no AS, 13% had mild, and 6% had moderate. White patients were more likely to be male and less likely to be on hemodialysis compared to black patients. No differences in AS severity (P=0.55) or age (60 vs. 58 years, P=0.34) were seen at baseline. In white vs. black patients, mean gradient increased at 1.90 (95% CI: 0.79, 3.01) mmHg/year vs. 1.46 (95% CI, 0.79, 2.14) mmHg/year, P=0.20, AVA decreased at -0.10 (95% CI: -0.15, -0.05) m2/year vs. -0.08 (95% CI: -0.11, -0.05) m2/year, P=0.13, and transvalvular velocity increased at 0.11 (95% CI: 0.04, 0.18) m/s/year vs. 0.07 (95% CI: 0.03, 0.11) m/s/year, P=0.09. CONCLUSIONS: Compared to black patients, white patients in an advanced CKD cohort may have exhibited more rapid progression of AS. Ours is the first study to analyze racial differences in such a population. A study with a larger sample size is needed to confirm our findings.