Asymptomatic people with well-controlled HIV do not have abnormal left ventricular global longitudinal strain.

Background: Previous studies have reported impairment in systolic and diastolic function in people with HIV (PWHIV). Our aim was to determine if echocardiographically measured left ventricular (LV) global longitudinal strain (GLS) is abnormal in asymptomatic PWHIV. Methods: A cross-sectional study of PWHIV (n = 98, 89% male, median age 53 years) and HIV-negative people (n = 50, median age 53 years) without known cardiovascular disease were recruited from a single centre. All participants completed a health/lifestyle questionnaire, provided a fasting blood sample, and underwent a comprehensive echocardiogram for assessment of diastolic and systolic LV function, including measurement of GLS. Results: All PWHIV were receiving antiretroviral therapy (ART) for a median of 12 years (IQR: 6.9, 22.4), the majority with good virological control (87% suppressed) and without immunological compromise (median CD4 598 cells/µl, IQR: 388, 841). Compared with controls of similar age and gender, there was no difference in GLS [mean GLS -20.3% (SD 2.5%) vs. -21.0% (SD 2.5%), p = 0.14] or left ventricular ejection fractions [65.3% (SD 6.3) vs. 64.8% (SD 4.8), p = 0.62]. Following adjustment for covariates (gender, heart rate, systolic and diastolic blood pressure, and fasting glucose), the difference in GLS remained non-significant. There were no differences in LV diastolic function between the groups. Exposure to at least one mitochondrially toxic ART drug (didanosine, stavudine, zidovudine, or zalcitabine) was not associated with impairment of LV systolic function. Conclusion: No clinically significant impairment of myocardial systolic function, as measured by LV GLS, was detected in this predominantly Caucasian male population of PWHIV on long-term ART, with no history of cardiovascular disease.

Vascular Responses Among Adults Four Years Post Exposure to 6 Weeks of Smoke from the Hazelwood Coal Mine Fire.

Background and Aims: Mega-wild fires are exposing large communities to weeks or months of high concentration smoke-related fine particulate air pollution (PM). However, little research has examined the long-term vascular responses from exposure to PM of this concentration and duration. We investigated whether level of exposure to 6 weeks of PM from the 2014 Hazelwood coal mine fire was associated with abnormal vascular responses approximately four years later. Methods: A cross-sectional analysis was undertaken of 387 participants (225 exposed, 162 unexposed) aged 55-89 years, 3.5-4 years after the mine fire. The primary outcome was flow-mediated dilatation (FMD), with time to reach peak diameter as the secondary outcome. Other secondary markers included high-sensitivity C-reactive protein (hsCRP) and ischaemic Electrocardiogram (ECG) changes. Results: There was no evidence of a difference in FMD between participants with high, medium, low or no mine-fire related PM2.5 exposure (4.09% vs 4.06% vs 4.02% vs 3.98%, respectively, p=0.99). Likewise, there was no difference in hsCRP or ischaemic ECG changes. In contrast, there was evidence of a difference in time to peak diameter (p=0.002) with more unexposed participants reaching peak diameter within 30 seconds (36%) compared to those who had high, medium, or low exposure (23%, 22%, 13%, respectively). Multivariate ordinal logistic regression analysis suggested that township, Morwell (exposed) vs Sale (unexposed), but not level of PM2.5 exposure, was associated with delayed time to peak diameter (OR 2.71; 95% CI 1.56, 4.69). Smokers also had delayed time to peak diameter. Conclusion: There was no association between level of exposure to PM2.5 from the 6-week Hazelwood coal mine fire smoke event and reduced FMD, elevated hsCRP or ischaemic ECG four years later. Evidence of delayed time to peak diameter observed in adults from the exposed town, compared to an unexposed town, requires further investigation.

Cardiopulmonary exercise performance and factors associated with aerobic capacity in neuromuscular diseases.

INTRODUCTION/AIMS: Aerobic deconditioning, due to lower levels of physical activity, could impact independence for people with neuromuscular conditions. We report the maximal cardiopulmonary response in a cohort of people with Charcot Marie Tooth disease type 1A (CMT 1A) and inclusion body myositis (IBM). We also explored potential predictors of aerobic capacity with measures of physical impairment and functional performance. METHODS: Participants underwent maximal cardiopulmonary exercise testing (CPET) using a semi-recumbent cycle ergometer. Data were analyzed to determine the peak O2 consumption (VO2 peak), anaerobic threshold (AT), maximum heart rate (MHR), ventilatory equivalent for CO2 slope (VE /VCO2 ), and respiratory exchange ratio (RER). Impairment, functional and patient reported measures were also recorded. Predicted CPET variables were calculated based on published normative data for age, gender, and weight. RESULTS: Twenty-two people with CMT and 17 people with IBM were recruited. Both groups showed significantly lower VO2 peak, MHR, AT, and VE /VCO2 . The CMT group overall performed better than the IBM group, with significantly higher VO2 peak, MHR, and AT, but lower VE /VCO2. Linear regression analysis demonstrated that VO2 peak was related to body fat percentage and 6-min walk distance for both groups, and steps per day for the IBM group. DISCUSSION: Lower than predicted CPET variables were observed that were not explained by cardiopulmonary limitations or reduced effort, implicating peripheral factors in limiting the cycling task. Regression analysis implied prediction of VO2 peak by body fat percentage and 6-min walk distance. Six-minute walk distance could be a potential proxy measure of cardiopulmonary fitness.

Markers of Cardiovascular Disease among Adults Exposed to Smoke from the Hazelwood Coal Mine Fire.

Little research has examined the effects of high concentration, medium-duration smoke exposure on cardiovascular health. We investigated whether six weeks of exposure to smoke from the 2014 Hazelwood coal mine fire in Victoria (Australia), was associated with long-term clinical or subclinical cardiovascular disease approximately four years later, in adult residents of the towns of Morwell (exposed, n = 336) and Sale (unexposed, n = 162). The primary outcome was serum high sensitivity (hs) C-reactive protein (CRP). Blood pressure, electrocardiogram, flow mediated dilatation and serum levels of hs-troponin, N-terminal pro B-type natriuretic peptide and lipids were secondary outcomes. There was no significant difference in weighted median hsCRP levels between exposed and unexposed participants (1.9 mg/L vs. 1.6 mg/L, p = 0.273). Other outcomes were comparable between the groups. hsCRP was associated in a predictable manner with current smoking, obesity and use of lipid-lowering therapy. Four years after a 6-week coal mine fire, this study found no association between smoke exposure and markers of clinical or subclinical cardiovascular disease in exposed adults.

Impact of rosuvastatin on atherosclerosis in people with HIV at moderate cardiovascular risk: a randomised, controlled trial.

BACKGROUND: People living with HIV-1 (PLHIV) are at increased risk for cardiovascular disease. OBJECTIVE: This study aimed to determine if PLHIV would benefit from starting statins at a lower threshold than currently recommended in the general population. DESIGN: A double-blind multicentre, randomised, placebo-controlled trial was performed. METHODS: Participants (n = 88) with well controlled HIV, at moderate cardiovascular risk (Framingham score of 10-15%), and not recommended for statins were recruited from Australia and Switzerland. They were randomized 1 : 1 to rosuvastatin (n = 44) 20 mg daily, 10 mg if co-administered with ritonavir/cobicistat-boosted antiretroviral therapy, or placebo (n = 40) for 96 weeks. Assessments including fasting blood collection and carotid--intima media thickness (CIMT) were performed at baseline, and weeks 48 and 96. The primary outcome was the change from baseline to week 96 in CIMT (clinicaltrials.gov: NCT01813357). RESULTS: Participants were predominantly men [82 (97.6%); mean age 54 years (SD 6.0)]. At 96 weeks, there was no difference in the progression of CIMT between the rosuvastatin (mean 0.004 mm, SE 0.0036) and placebo (0.0062 mm, SE 0.0039) arms (P = 0.684), leading to no difference in CIMT levels between groups at week 96 [rosuvastatin arm, 0.7232 mm (SE 0.030); placebo arm 0.7785 mm (SE 0.032), P = 0.075].Adverse events were common (n = 146) and predominantly in the rosuvastatin arm [108 (73.9%)]. Participants on rosuvastatin were more likely to cease study medication because of an adverse event [7 (15.9%) vs. 2 (5.0%), P = 0.011]. CONCLUSION: In PLHIV, statins prescribed at a lower threshold than guidelines did not lead to improvements in CIMT but was associated with significant adverse events.

HIV disease, metabolic dysfunction and atherosclerosis: A three year prospective study.

HIV infection is known to be associated with cardiometabolic abnormalities; here we investigated the progression and causes of these abnormalities. Three groups of participants were recruited: HIV-negative subjects and two groups of treatment-naïve HIV-positive subjects, one group initiating antiretroviral treatment, the other remaining untreated. Intima-media thickness (cIMT) increased in HIV-positive untreated group compared to HIV-negative group, but treatment mitigated the difference. We found no increase in diabetes-related metabolic markers or in the level of inflammation in any of the groups. Total cholesterol, low density lipoprotein cholesterol and apoB levels were lower in HIV-positive groups, while triglyceride and Lp(a) levels did not differ between the groups. We found a statistically significant negative association between viral load and plasma levels of total cholesterol, LDL cholesterol, HDL cholesterol, apoA-I and apoB. HIV-positive patients had hypoalphalipoproteinemia at baseline, and we found a redistribution of sub-populations of high density lipoprotein (HDL) particles with increased proportion of smaller HDL in HIV-positive untreated patients, which may result from increased levels of plasma cholesteryl ester transfer protein in this group. HDL functionality declined in the HIV-negative and HIV-positive untreated groups, but not in HIV-positive treated group. We also found differences between HIV-positive and negative groups in plasma abundance of several microRNAs involved in lipid metabolism. Our data support a hypothesis that cardiometabolic abnormalities in HIV infection are caused by HIV and that antiretroviral treatment itself does not influence key cardiometabolic parameters, but mitigates those affected by HIV.

Community exercise is feasible for neuromuscular diseases and can improve aerobic capacity.

OBJECTIVE: The aim of this phase 2 trial was to ascertain the feasibility and effect of community-based aerobic exercise training for people with 2 of the more common neuromuscular diseases: Charcot-Marie-Tooth disease type 1A (CMT) and inclusion body myositis (IBM). METHODS: A randomized single-blinded crossover trial design was used to compare a 12-week aerobic training program using recombinant exercise bicycles compared to a control period. The training occurred 3 times per week in community gyms local to the participants. Support was available from trained gym staff and a research physiotherapist. The 2 disease groups were analyzed separately. The primary outcome measure was peak oxygen uptake (VO2 peak) during a maximal exercise test, with secondary measures of muscle strength, function, and patient-reported measures. RESULTS: Data from 23 people with CMT and 17 people with IBM were included in the analysis. Both disease groups had high levels of participation and demonstrated improvements in VO2 peak, with a moderate effect size in the CMT participants (Cohen d = 0.53) and a strong effect size in the IBM group (Cohen d = 1.72). No major changes were observed in the secondary outcome measures. Qualitative interviews revealed that participants valued the support of gym instructors and the research physiotherapists in overcoming challenges to participation. CONCLUSION: Twelve weeks of aerobic training in community gyms was feasible, safe, and improved aerobic capacity in people with CMT and IBM. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with CMT type 1A and IBM, an aerobic training program increases aerobic capacity.

A study of physical activity comparing people with Charcot-Marie-Tooth disease to normal control subjects.

PURPOSE: Charcot Marie Tooth disease (CMT) describes a group of hereditary neuropathies that present with distal weakness, wasting and sensory loss. Small studies indicate that people with CMT have reduced daily activity levels. This raises concerns as physical inactivity increases the risk of a range of co- morbidities, an important consideration in the long-term management of this disease. This study aimed to compare physical activity, patterns of sedentary behavior and overall energy expenditure of people with CMT and healthy matched controls. METHODS: We compared 20 people with CMT and 20 matched controls in a comparison of physical activity measurement over seven days, using an activity monitor. Patterns of sedentary behavior were explored through a power law analysis. RESULTS: Results showed a decrease in daily steps taken in the CMT group, but somewhat paradoxically, they demonstrate shorter bouts of sedentary activity and more frequent transitions from sedentary to active behaviors. No differences were seen in energy expenditure or time spent in sedentary, moderate or vigorous activity. CONCLUSION: The discrepancy between energy expenditure and number of steps could be due to higher energy requirements for walking, but also may be due to an over-estimation of energy expenditure by the activity monitor in the presence of muscle wasting. Alternatively, this finding may indicate that people with CMT engage more in activities or movement not related to walking. Implications for Rehabilitation Charcot-Marie-Tooth disease: • People with Charcot-Marie-Tooth disease did not show a difference in energy expenditure over seven days compared to healthy controls, but this may be due to higher energy costs of walking, and/or an over estimation of energy expenditure by the activity monitor in a population where there is muscle wasting. This needs to be considered when interpreting activity monitor data in people with neuromuscular diseases. • Compared to healthy controls, people with Charcot-Marie-Tooth disease had a lower step count over seven days, but exhibited more frequent transitions from sedentary to active behaviors • High Body Mass Index and increased time spent sedentary were related factors that have implications for general health status. • Understanding the profile of physical activity and behavior can allow targeting of rehabilitation interventions to address mobility and fitness.

Predictive Performance of Echocardiographic Parameters for Cardiovascular Events Among Elderly Treated Hypertensive Patients.

BACKGROUND: Hypertension leads to cardiac structural and functional changes, commonly assessed by echocardiography. In this study, we assessed the predictive performance of different echocardiographic parameters including left ventricular hypertrophy (LVH) on future cardiovascular outcomes in elderly hypertensive patients without heart failure. METHODS: Data from LVH substudy of the Second Australian National Blood Pressure trial were used. Echocardiograms were performed at entry into the study. Cardiovascular outcomes were identified over short term (median 4.2 years) and long term (median 10.9 years). LVH was defined using threshold values of LV mass (LVM) indexed to either body surface area (BSA) or height(2.7): >115/95g/m(2) (LVH-BSA(115/95)) or ≥49/45g/m(2.7) (LVH-ht(49/45)) in males/females, respectively, and ≥125g/m(2) (LVH-BSA(125)) or ≥51g/m(2.7) (LVH-ht(51)) for both sexes. RESULTS: In the 666 participants aged ≥65 years in this analysis, LVH prevalence at baseline was 33%-70% depending on definition; and after adjusting for potential risk factors, only LVH-BSA(115/95) predicted both short- and long-term cardiovascular outcomes. Participants having LVH-BSA(115/95) (69%) at baseline had twice the risk of having any first cardiovascular event over the short term (hazard ratio, 95% confidence interval: 2.00, 1.12-3.57, P = 0.02) and any fatal cardiovascular events (2.11, 1.21-3.68, P = 0.01) over the longer term. Among other echocardiographic parameters, LVM and LVM indexed to either BSA or height(2.7) predicted cardiovascular events over both short and longer term. CONCLUSIONS: In elderly treated hypertensive patients without heart failure, determining LVH by echocardiography is highly dependent on the methodology adopted. LVH-BSA(115/95) is a reliable predictor of future cardiovascular outcomes in the elderly.

Accuracy of Echocardiographic Cardiac Index Assessment in Subjects with Preserved Left Ventricular Ejection Fraction.

INTRODUCTION: We aimed to determine the accuracy of the echocardiographic assessment of cardiac index (CI) in subjects with preserved left ventricular ejection fraction (LVEF). METHODS: Thirty-three subjects with LVEF >50%, normal sinus rhythm, and a broad spectrum of hemodynamic profiles underwent echocardiography immediately followed by right heart catheterization. As gold standards, CI was assessed using thermodilution [CI (TD)] and the Fick method [CI (F)]. Echocardiographic CI was assessed by four methods: from the left ventricular outflow tract (LVOT) velocity time integral and the LVOT diameter as measured [CI (LVOTm)] as well as estimated from body surface area [CI (LVOTe)], and from stroke volume indices assessed using the biplane [CI (BP)] and monoplane [CI (MP)] methods. RESULTS: The mean CI (TD), CI (F), CI (LVOTm), CI (LVOTe), CI (BP), and CI (MP) were 3.0 ± 0.9, 3.1 ± 0.7, 2.8 ± 0.6, 3.3 ± 0.6, 2.0 ± 0.6, and 2.2 ± 0.7 L/min/m(2) . There were modest correlations between CI (TD) and CI (F) and all four noninvasive measures of CI with r(2) values ranging from 0.09 to 0.30. CI (LVOTm) underestimated CI (TD) and CI (F) by 0.3 and 0.3 L/min/m(2) , CI (LVOTe) overestimated CI (TD) and CI (F) by 0.3 and 0.2 L/min/m(2) , and CI (BP) and CI (MP) underestimated CI (TD) and CI (F) by 1.1 and 1.1 L/min/m(2) and 0.9 and 0.9 L/min/m(2) , respectively, with large limits of agreement for all comparisons. CONCLUSIONS: In subjects with nondilated left ventricles with preserved LVEF, flow- or volume-based measures of CI by 2D echocardiography may not accurately reflect CI (TD) and CI (F). Further larger studies are required to verify our findings and to evaluate the accuracy of contrast and 3D echocardiography in this setting.

A pilot study of proximal strength training in Charcot-Marie-Tooth disease.

Gait analysis of people with Charcot-Marie-Tooth (CMT) disease revealed proximal adaptive gait strategies to compensate for foot drop. We previously demonstrated that hip flexor muscle fatigue can limit walking endurance. This pilot study used a single-blinded cross over design to investigate the effect of a 16-week home-based programme of resistance training on hip flexor muscle strength. Measures of walking endurance, gait speed, exertion, fatigue, and general activity were also recorded. The exercise protocol was based on American College of Sports Medicine recommendations. A mixed effects model was used for analysis. Twenty-six people finished the study, with average reported exercise participation of 93%. No negative effects of exercise were observed. Significant increase in hip flexor muscle strength was observed on the left, but not the right. No changes were observed in walking speed and endurance measures. This pilot study of home-based resistance training showed a modest improvement in hip strength but only on one side. The lack of a more significant improvement and no improvement in walking measures suggests that this training protocol may not be optimal for people with CMT and that patients may need to stratified differently for training studies in CMT.

Associations between surface markers on blood monocytes and carotid atherosclerosis in HIV-positive individuals.

Chronic HIV infection is associated with increased risk of cardiovascular disease (CVD), including in patients with virological suppression. Persistent innate immune activation may contribute to the development of CVD via activation of monocytes in these patients. We investigated whether changes in monocyte phenotype predict subclinical atherosclerosis in virologically suppressed HIV-positive individuals with low cardiovascular risk. We enroled 51 virologically suppressed HIV-positive individuals not receiving protease inhibitors or statins and 49 age-matched uninfected controls in this study. Carotid artery intima-media thickness (cIMT) was used as a surrogate marker for CVD, and traditional risk factors, including Framingham risk scores, were recorded. Markers of monocyte activation (CD14, CD16, CCR2, CX3CR1, CD38, HLA-DR and CD11b) were measured in whole-blood samples by flow cytometry. Associations were assessed using univariate and multivariate median regressions. Median cIMT was similar between HIV-positive and HIV-negative participants (P=0.3), although HIV-positive patients had significantly higher Framingham risk score (P=0.009) and systemic inflammation. Expression of two monocyte markers, CD11b and CX3CR1, independently predicted carotid artery thickness in HIV-positive individuals after controlling for Framingham risk score (P=0.025 and 0.015, respectively). These markers were not predictive of carotid artery thickening in controls. Our study indicates that monocyte surface markers may serve as novel predictors of CVD in HIV-positive individuals and is consistent with an important role for monocyte activation in the progression of HIV-related cardiovascular pathology.

The effect of HIV infection on atherosclerosis and lipoprotein metabolism: a one year prospective study.

OBJECTIVES: HIV infection is associated with dyslipidaemia and increased risk of cardiovascular disease. The effects of HIV infection and antiretroviral treatment on surrogate markers of atherosclerosis, and lipoprotein metabolism were evaluated in a 12 month prospective study. METHODS AND RESULTS: Treatment-naive HIV patients were recruited into one of three groups: untreated HIV infection not likely to require initiation of antiretroviral therapy (ART) for at least 12 months; initiating treatment with non nucleoside reverse transcriptase inhibitor-containing ART regimen and initiating treatment with protease inhibitor-containing ART regimen. The patients underwent assessment of carotid intima-media thickness (cIMT), pulse wave velocity (PWV), brachial flow-mediated dilation (FMD) and variables of plasma lipoprotein metabolism at baseline and 12 months. The findings were compared with published values for age and sex matched HIV-negative healthy subjects in a cross-sectional fashion. cIMT and FMD were lower while PWV was higher in HIV-patients compared with HIV-negative individuals; none of the markers changed significantly during 12 months follow up. HIV patients had hypoalphalipoproteinemia and elevated plasma levels of lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein. The only significant changes in lipid-related variables were elevation of total cholesterol and triglycerides in patients treated with PI-containing regimen and elevation of plasma LCAT levels in patients treated with NNRTI-containing regimen. The ability of whole and apoB-depleted plasma to effect cholesterol efflux was not impaired in all three groups. CONCLUSIONS: This study did not find evidence for rapid progression of subclinical atherosclerosis and deterioration of dyslipidaemia in HIV patients within 1 year.

Accuracy of Doppler echocardiography to estimate key hemodynamic variables in subjects with normal left ventricular ejection fraction.

BACKGROUND: The accuracy of Doppler echocardiography to estimate key hemodynamic parameters in subjects with normal left ventricular ejection fraction (LVEF) has not been fully investigated. METHODS AND RESULTS: Thirty-six subjects with LVEF >50% (median age 62 years), with a broad clinical profile, underwent Doppler echocardiography immediately followed by right heart catheterization. Correlation coefficients between invasive and noninvasive right atrial pressure (RAP), systolic (sPAP) and mean (mPAP) pulmonary artery pressure, cardiac output (CO), and pulmonary vascular resistance (PVR) were 0.39, 0.70, 0.72, 0.57, and 0.60 (P < .001 for all). There was no significant correlation between invasive and noninvasive (based on the peak early transmitral to peak early septal mitral annular velocity ratio) pulmonary capillary wedge pressure (PCWP; r = 0.23; P = .18). Bland-Altman plots revealed variable bias but with consistently large limits of agreement for all noninvasive parameters, particularly PCWP. Areas under the receiver operating characteristic curve for noninvasive sPAP, CO, PVR, and PCWP to predict an invasively assessed mPAP ≥25 mm Hg, cardiac index <2.5 L min(-1) m(-2), PVR >3 Wood units, and PCWP ≤15 mm Hg, respectively, were 0.92, 0.83, 0.70, and 0.58. CONCLUSIONS: Single Doppler echocardiography parameters are not accurate enough to reliably estimate key hemodynamic parameters, particularly PCWP, in subjects with normal LVEF.

Large-artery stiffness contributes to the greater prevalence of systolic hypertension in elderly women.

OBJECTIVES: To determine whether sex differences in large-artery stiffness contribute to the greater prevalence of systolic hypertension in elderly women than in elderly men. DESIGN: During a single visit arterial stiffness was assessed in the unmedicated state using four parameters. PARTICIPANTS: Three hundred seventy-four women with a mean age+/-standard deviation of 72+/-5 and 296 men aged 71+/-5 participated. SETTING: Hypertensive patients were recruited from general practice as part of the second Australian National Blood Pressure Study in Melbourne, Australia. MEASUREMENTS: Large-artery stiffness was assessed using multiple methodologies, including aortic arch stiffness (beta-index) using M-mode ultrasound and arterial compliance and augmentation index using noninvasive carotid pressure and aortic flow measurements. RESULTS: Women had greater carotid and brachial pulse pressure (PP) than men (P<.001), despite higher mean arterial pressure in men. Mean arterial compliance was lower in women (0.20+/-0.12 vs 0.28+/-0.16 mL/mmHg, P<.001) even after correction for aortic area, and aortic arch stiffness was higher (30+/-36 vs 23+/-22; P<.01). Consistent with both a stiffer proximal circulation and a shorter distance to reflection sites, women had higher augmentation index (38+/-11% vs 29+/-12%, P<.001). In multivariate analysis, sex was an independent determinant of all arterial stiffness indices. CONCLUSION: Independently of known confounders, elderly hypertensive women have stiffer large arteries, greater central wave reflection, and higher PP than elderly men. Stiffer large arteries likely contribute to the greater prevalence of systolic hypertension in elderly women and may partly explain the acceleration in postmenopausal cerebrovascular and cardiac complications.