Pacemaker detected active minutes are superior to pedometer-based step counts in measuring the response to physical activity counseling in sedentary older adults.

BACKGROUND: In patients with permanent pacemakers (PPM), physical activity (PA) can be monitored using embedded accelerometers to measure pacemaker detected active hours (PDAH), a strong predictor of mortality. We examined the impact of a PA Counseling (PAC) intervention on increasing activity as measured by PDAH and daily step counts. METHODS: Thirteen patients (average age 80 ± 6 years, 84.6% women) with implanted Medtronic PPMs with a ≤ 2 PDAH daily average were included in this study. Patients were randomized to Usual Care (UC, N = 6) or a Physical Activity Counseling Intervention (PACI, N = 7) groups. Step count and PDAH data were obtained at baseline, following a 12-week intervention, then 12 weeks after intervention completion. Data were analyzed using independent t-tests, Pearson's r, chi-square, and general linear models for repeated measures. RESULTS: PDAH significantly differed by time point for all subject combined (P = 0.01) but not by study group. Subjects with baseline gait speeds of > 0.8 m/sec were responsible for the increases in PDAH observed. Step counts did not differ over time in the entire cohort or by study group. Step count and PDAH significantly correlated at baseline (r = 0.60, P = 0.03). This correlation disappeared by week 12. CONCLUSION(S): PDAH can be used to monitor PA and PA interventions and may be superior to hip-worn pedometers in detecting activity. A significant increase in PA, regardless of treatment group, suggests that patient awareness of the ability to monitor PA through a PPM increases PA in these patients, particularly in patients with gait speeds of < 0.8 m/sec. TRIAL REGISTRATION: ClincalTrials.gov NCT03052829. Date of Registration: 2/14/2017.

Circulating levels of mitochondrial uncoupling protein 2, but not prohibitin, are lower in humans with type 2 diabetes and correlate with brachial artery flow-mediated dilation.

BACKGROUND: Excessive reactive oxygen species from endothelial mitochondria in type 2 diabetes individuals (T2DM) may occur through multiple related mechanisms, including production of mitochondrial reactive oxygen species (mtROS), inner mitochondrial membrane (Δψm) hyperpolarization, changes in mitochondrial mass and membrane composition, and fission of the mitochondrial networks. Inner mitochondrial membrane proteins uncoupling protein-2 (UCP2) and prohibitin (PHB) can favorably impact mtROS and mitochondrial membrane potential (Δψm). Circulating levels of UCP2 and PHB could potentially serve as biomarker surrogates for vascular health in patients with and without T2DM. METHODS: Plasma samples and data from a total of 107 individuals with (N = 52) and without T2DM (N = 55) were included in this study. Brachial artery flow mediated dilation (FMD) was measured by ultrasound. ELISA was performed to measure serum concentrations of PHB1 and UCP2. Mitochondrial membrane potential was measured from isolated leukocytes using JC-1 dye. RESULTS: Serum UCP2 levels were significantly lower in T2DM subjects compared to control subjects (3.01 ± 0.34 vs. 4.11 ± 0.41 ng/mL, P = 0.04). There were no significant differences in levels of serum PHB. UCP2 levels significantly and positively correlated with FMDmm (r = 0.30, P = 0.03) in T2DM subjects only and remained significant after multivariable adjustment. Within T2DM subjects, serum PHB levels were significantly and negatively correlated with UCP2 levels (ρ = - 0.35, P = 0.03). CONCLUSION: Circulating UCP2 levels are lower in T2DM patients and correlate with endothelium-dependent vasodilation in conduit vessels. UCP2 could be biomarker surrogate for overall vascular health in patients with T2DM and merits additional investigation.

Impact of DPP-4 inhibition on acute and chronic endothelial function in humans with type 2 diabetes on background metformin therapy.

Cell culture and animal work indicate that dipeptidyl peptidase-4 (DPP-4) inhibition may exert cardiovascular benefits through favorable effects on the vascular endothelium. Prior human studies evaluating DPP-4 inhibition have shown conflicting results that may in part be related to heterogeneity of background anti-diabetes therapies. No study has evaluated the acute response of the vasculature to DPP-4 inhibition in humans. We recruited 38 patients with type 2 diabetes on stable background metformin therapy for a randomized, double-blind, placebo-controlled crossover trial of DPP-4 inhibition with sitagliptin (100 mg/day). Each treatment period was 8 weeks long separated by 4 weeks of washout. Endothelial function and plasma markers of endothelial activation (intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)) were measured prior to and 2 hours following acute dosing of sitagliptin or placebo, as well as following 8 weeks of intervention with each pill. Thirty subjects completed the study and were included in analyses. Neither acute nor chronic sitagliptin therapy resulted in significant changes in vascular endothelial function. While post-acute sitagliptin ICAM-1 levels were lower than that post-chronic sitagliptin, the ICAM-1 concentration was not significantly different than pre-acute sitagliptin levels or levels measured in relationship to placebo. There were no significant changes in plasma VCAM-1 levels at any time point. Acute and chronic sitagliptin therapies have neutral effects on the vascular endothelium in the setting of metformin background therapy. In conclusion, our findings suggest DPP-4 inhibition has a neutral effect on cardiovascular risk in patients without a history of heart failure or renal insufficiency. TRIAL REGISTRATION: NCT01859793.

Lactobacillus plantarum 299v probiotic supplementation in men with stable coronary artery disease suppresses systemic inflammation.

Recent trials demonstrate that systemic anti-inflammatory therapy reduces cardiovascular events in coronary artery disease (CAD) patients. We recently demonstrated Lactobacillus plantarum 299v (Lp299v) supplementation improved vascular endothelial function in men with stable CAD. Whether this favorable effect is in part due to anti-inflammatory action remains unknown. Testing this hypothesis, we exposed plasma obtained before and after Lp299v supplementation from these subjects to a healthy donor's PBMCs and measured differences in the PBMC transciptome, performed gene ontological analyses, and compared Lp299v-induced transcriptome changes with changes in vascular function. Daily alcohol users (DAUs) (n = 4) had a significantly different response to Lp299v and were separated from the main analyses. Non-DAUs- (n = 15) showed improved brachial flow-mediated dilation (FMD) and reduced circulating IL-8, IL-12, and leptin. 997 genes were significantly changed. I.I.com decreased (1.01 ± 0.74 vs. 0.22 ± 0.51; P < 0.0001), indicating strong anti-inflammatory effects. Pathway analyses revealed downregulation of IL-1ß, interferon-stimulated pathways, and toll-like receptor signaling, and an increase in regulator T-cell (Treg) activity. Reductions in GBP1, JAK2, and TRAIL expression correlated with improved FMD. In non-DAU men with stable CAD, post-Lp299v supplementation plasma induced anti-inflammatory transcriptome changes in human PBMCs that could benefit CAD patients. Future studies should delineate changes in circulating metabolites responsible for these effects.

Risk of new-onset atrial fibrillation in elderly patients with the overlap syndrome: a retrospective cohort study.

OBJECTIVE: Co-existence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) is referred to as overlap syndrome. Overlap patients have greater degree of hypoxia and pulmonary hypertension than patients with OSA or COPD alone. Studies showed that elderly patients with OSA alone do not have increased risk of atrial fibrillation (AF) but it is not known if overlap patients have higher risk of AF. To determine whether elderly patients with overlap syndrome have an increased risk of AF. METHODS: In this single center, community-based retrospective cohort analysis, data were collected on 2,873 patients > 65 years of age without AF, presenting in the year 2006. Patients were divided into OSA group (n = 60), COPD group (n = 416), overlap syndrome group (n = 28) and group with no OSA or COPD (n = 2369). The primary endpoint was incidence of new-onset AF over the following two years. Logistic regression was performed to adjust for heart failure (HF), coronary artery disease, hypertension (HTN), cerebrovascular disease, cardiac valve disorders, diabetes mellitus, hyperlipidemia, chronic kidney disease (CKD) and obesity. RESULTS: The incidence of AF was 10% in COPD group, 6% in OSA group and 21% in overlap syndrome group (P < 0.05). After adjusting for age, sex, HF, CKD, and HTN, patients with overlap syndrome demonstrated a significant association with new-onset AF (OR = 3.66, P = 0.007). HF, CKD and HTN were also significantly associated with new-onset AF (P < 0.05). CONCLUSION: Among elderly patients, the presence of overlap syndrome is associated with a marked increase in risk of new-onset AF as compared to the presence of OSA or COPD alone.

The impact of severe acidemia on neurologic outcome of cardiac arrest survivors undergoing therapeutic hypothermia.

INTRODUCTION: Therapeutic Hypothermia (TH) has become a standard of care in improving neurological outcomes in cardiac arrest (CA) survivors. Previous studies have defined severe acidemia as plasma pH<7.20. We investigated the influence of severe acidemia at the time of initiation of TH on neurological outcome in CA survivors. METHODS: A retrospective analysis was performed on 196 consecutive CA survivors (out-of-hospital CA and in-hospital CA) who underwent TH with endovascular cooling between January 2007 and October 2012. Arterial blood gas drawn prior to initiation of TH was utilized to measure pH in all patients. Shockable and non-shockable CA patients were divided into two sub-groups based on pH (pH<7.2 and pH≥7.2). The primary end-point was measured using the Pittsburgh Cerebral Performance Category (CPC) scale prior to discharge from the hospital: good (CPC 1 and 2) and poor (CPC 3 to 5) neurologic outcome. RESULTS: Sixty-two percent of shockable CA patients with pH≥7.20 had good neurological outcome as compared to 34% patients with pH<7.20. Shockable CA patients with pH≥7.20 were 3.3 times more likely to have better neurological outcome when compared to those with pH <7.20 [p=0.013, OR 3.3, 95% CI (1.28-8.45)]. In comparison, non-shockable CA patients with p≥7.20 did not have a significantly different neurological outcome as compared to those with pH<7.20 [p=0.97, OR 1.02, 95% CI (0.31-3.3)]. CONCLUSION: Presence of severe acidemia at initiation of TH in shockable CA survivors is significantly associated with poor neurological outcomes. This effect was not observed in the non-shockable CA survivors.