Cardiopulmonary exercise testing in severe osteoarthritis: a crossover comparison of four exercise modalities.

Cardiopulmonary exercise testing is performed increasingly for cardiorespiratory fitness assessment and pre-operative risk stratification. Lower limb osteoarthritis is a common comorbidity in surgical patients, meaning traditional cycle ergometry-based cardiopulmonary exercise testing is difficult. The purpose of this study was to compare cardiopulmonary exercise testing variables and subjective responses in four different exercise modalities. In this crossover study, 15 patients with osteoarthritis scheduled for total hip or knee arthroplasty (mean (SD) age 68 (7) years; body mass index 31.4 (4.1) kg.m-2 ) completed cardiopulmonary exercise testing on a treadmill, elliptical cross-trainer, cycle and arm ergometer. Mean (SD) peak oxygen consumption was 20-30% greater on the lower limb modalities (treadmill 21.5 (4.6) (p < 0.001); elliptical cross-trainer (21.2 (4.1) (p < 0.001); and cycle ergometer (19.4 (4.2) ml.min-1 .kg-1 (p = 0.001), respectively) than on the arm ergometer (15.7 (3.7) ml.min-1 .kg-1 ). Anaerobic threshold was 25-50% greater on the lower limb modalities (treadmill 13.5 (3.1) (p < 0.001); elliptical cross-trainer 14.6 (3.0) (p < 0.001); and cycle ergometer 10.7 (2.9) (p = 0.003)) compared with the arm ergometer (8.4 (1.7) ml.min-1 .kg-1 ). The median (95%CI) difference between pre-exercise and peak-exercise pain scores was greater for tests on the treadmill (2.0 (0.0-5.0) (p = 0.001); elliptical cross-trainer (3.0 (2.0-4.0) (p = 0.001); and cycle ergometer (3.0 (1.0-5.0) (p = 0.001)), compared with the arm ergometer (0.0 (0.0-1.0) (p = 0.406)). Despite greater peak exercise pain, cardiopulmonary exercise testing modalities utilising the lower limbs affected by osteoarthritis elicited higher peak oxygen consumption and anaerobic threshold values compared with arm ergometry.

Childhood body mass index and endothelial dysfunction evaluated by peripheral arterial tonometry in early midlife.

BACKGROUND/OBJECTIVES: Endothelial dysfunction predicts mortality but it is unknown whether childhood obesity predicts adult endothelial dysfunction. The aim of this study was to determine whether anthropometric indices of body fat in childhood, adolescence and early midlife are associated with endothelial dysfunction in early midlife. SUBJECTS/METHODS: Participants belonged to a representative birth cohort of 1037 individuals born in Dunedin, New Zealand in 1972 and 1973 and followed to age 38 years, with 95% retention (the Dunedin Multidisciplinary Health and Development Study). We assessed anthropometric indices of obesity at ages 3, 5, 7, 9, 11, 13, 15, 18, 21, 26, 32 and 38 years. We tested associations between endothelial function assessed by peripheral arterial tonometry (PAT) at age 38 and; age 38 cardiovascular risk factors; age 3 body mass index (BMI); and four BMI trajectory groups from childhood to early midlife. RESULTS: Early midlife endothelial dysfunction was associated with BMI, large waist circumference, low high-density lipoprotein cholesterol, low cardiorespiratory fitness and increased high-sensitivity C-reactive protein. After adjustment for sex and childhood socioeconomic status, 3-year-olds with BMI 1 s.d. above the mean had Framingham-reactive hyperemia index (F-RHI) ratios that were 0.10 below those with normal BMI (ß=-0.10, 95% confidence interval (CI) -0.17 to -0.03, P=0.007) at age 38. Cohort members in the 'overweight', 'obese' and 'morbidly obese' trajectories had F-RHI ratios that were 0.08 (ß=-0.08, 95% CI -0.14 to -0.03, P=0.003), 0.13 (ß=-0.13, 95% CI -0.21 to -0.06, P<0.001) and 0.17 (ß=-0.17, 95% CI -0.33 to -0.01, P=0.033), respectively, below age-peers in the 'normal' trajectory. CONCLUSIONS: Childhood BMI and the trajectories of BMI from childhood to early midlife predict endothelial dysfunction evaluated by PAT in early midlife.

Comparison of three targeted approaches to screening for abdominal aortic aneurysm based on cardiovascular risk.

BACKGROUND: Abdominal aortic aneurysm (AAA) continues to be a significant health burden yet few countries have implemented a comprehensive screening programme. Screening typically places emphasis on men aged over 65 years; however, there is concern that other at-risk groups may be underidentified. The present study examined three potential screening strategies based on cardiovascular risk. METHODS: The prevalence of AAA was determined by abdominal ultrasound imaging in over 50-year-olds of either sex undergoing coronary angiography, vascular laboratory assessment of peripheral arterial disease, or community-based cardiovascular disease (CVD) event risk assessment. A fourth group, consisting of volunteers aged over 60 years who had no symptoms or signs of cardiovascular disease, was used as a comparator group. RESULTS: A total AAA prevalence of 4·4 per cent was detected across all three strategies (137 of 3142 individuals), compared with 1·0 per cent in the CVD-free group. Male sex, age and smoking were all associated with greater AAA prevalence. Although AAA prevalence was lowest using the community-based strategy, those with an AAA detected were on average 7 years younger than those with AAAs detected with the other two strategies (P < 0·001). CONCLUSION: Different strategies, based on CVD risk, resulted in AAA prevalence rates that were significantly greater than that in CVD-free individuals. This may provide opportunities for a targeted approach to community AAA screening in parts of the world where more sophisticated national screening programmes do not exist.

Variation in Arterial Access for Invasive Coronary Procedures in New Zealand: A National Analysis (ANZACS-QI 5).

BACKGROUND: Radial arterial access (RA) and femoral arterial access (FA) rates for invasive coronary angiography (ICA) vary widely internationally. The European Society of Cardiology (ESC) suggests default RA is feasible. We aim to investigate the variation in RA rates across all New Zealand public hospitals. METHODS AND RESULTS: Patient characteristics, procedural details, and inpatient outcome data were collected in the All New Zealand Acute Coronary Syndrome - Quality Improvement (ANZACS-QI) registry on consecutive patients undergoing ICA over five months. Of the 5894 ICAs 81% were via RA. Hospitals averaged 25 - 176 procedures/month (46.5% - 96.4% via RA). Operators averaged 17 procedures/month. Those performing more than 20 ICAs/month had RA rates between 61% - 99%. Of the 75 operators, 69% met the ESC recommendation. After multivariable adjustment higher operator (RR 1.12, CI 1.09 - 1.30) and hospital (RR 1.21, CI 1.15 - 1.28) volume were independent predictors of RA. Those with prior CABG (RR 0.51, CI 0.45 - 0.57), STEMI <12h (RR 0.91, CI 0.87 - 0.96), and female sex (RR 0.96, CI 0.94 - 0.99) were less likely to receive RA. CONCLUSIONS: New Zealand has a high RA rate for ICAs. Rates vary substantially between both operators and centres. Radial arterial was highest amongst the highest volume operators and centres.

Prevalence of abdominal aortic aneurysm in patients referred for transthoracic echocardiography.

BACKGROUND: Previous studies have documented the prevalence of abdominal aortic aneurysm (AAA) during transthoracic echocardiography, but the effect of such screening on subsequent vascular interventions remains unclear. AIM: This study aimed to determine the utility of opportunistic selective screening for AAA in a contemporary large series of patients having transthoracic echocardiography. METHODS: Subjects aged 50 years or older having transthoracic echocardiography had scanning of the infrarenal aorta in a consecutive series of 10 403 men and women. RESULTS: The study subjects had a mean age of 70.2 ± 10.7 years, and 54.1% were men. There was a 3.5% (95% confidence interval (CI) 3.2-3.9%) prevalence of AAA with a median diameter of 39 mm (interquartile range 32 mm-48 mm). In males ≥ 65 years the prevalence of newly diagnosed AAA was 6.2% (95% CI 5.5-7.0%). Of those with newly diagnosed AAA, 39.7% underwent AAA repair. Age and male gender were associated with AAA prevalence. After adjustment for age and gender, echocardiographic variables associated with AAA were left ventricular end diastolic dimension (odds ratio (OR) 1.02, 95%CI 1.01-1.04), interventricular septum thickness (OR 1.11, 95% CI 1.06-1.17), left ventricular posterior wall thickness (OR 1.09, 95% CI 1.03-1.15), left atrial diameter (OR 1.04, 95% CI 1.02-1.07) and aortic root diameter (OR 1.09, 95% CI 1.06-1.11). CONCLUSIONS: This study revealed a high prevalence of newly diagnosed AAA in a group of older men having cardiac evaluation. There was a relationship of increasing age with AAA, and a significant proportion of newly diagnosed subjects were not suitable for AAA repair.

Intra-individual changes of active matrix metalloproteinase-9 are associated with clinical in-stent restenosis of bare metal stents.

OBJECTIVES: Increased chronic postprocedural levels of active matrix metalloproteinase-9 (MMP-9) have been associated retrospectively with a history of in-stent restenosis (ISR). This study aimed to determine whether index or post-percutaneous coronary intervention (PCI) plasma levels of active MMP-9 are a predictor of subsequent clinical ISR, in a standard population of patients treated with bare metal coronary stents. METHODS: Four hundred thirty-two patients were prospectively recruited and sampled at index and 3 and 6 months after PCI. Those who developed symptomatic angiographically confirmed ISR were compared to randomly selected, asymptomatic controls, stratified by index presentation in a nested case-control design. Plasma samples were analyzed for the active form of MMP-9. RESULTS: In all, 35 patients (8.1%) developed ISR, and these were compared to 98 controls. The increase in active MMP-9 over 3 months was significantly greater in the ISR group (p = 0.030) and independent of the established risk factors. Index clinical presentation was not associated with acute changes in active MMP-9; however, patients with ST-elevation myocardial infarction had greater increases in active MMP-9 at 3 months. CONCLUSIONS: The change in active MMP-9 over 3 months after bare metal coronary stent placement appears to be independently associated with the development of ISR in a standard PCI population.

Pro-MMP-9/TIMP-1 ratio correlates poorly with a direct assessment of MMP-9 activity.

OBJECTIVE: To determine if the pro-MMP-9/TIMP-1 ratio is an accurate surrogate for endogenously active MMP-9 levels. METHODS: Plasma active MMP-9, pro-MMP-9 and TIMP-1 were measured in 295 patients. RESULTS: There was a weak negative correlation between the pro-MMP-9/TIMP-1 ratio and active MMP-9. TIMP-1 was more closely correlated with active MMP-9 than pro-MMP-9. CONCLUSION: Pro-MMP-9/TIMP-1 ratio measured with ELISA is not a good surrogate measure for active MMP-9, and direct measurements of active MMP-9 are therefore recommended.

Seasonal variation and stability of matrix metalloproteinase-9 activity and tissue inhibitor of matrix metalloproteinase-1 with storage at -80°C.

OBJECTIVE: To determine whether active matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 displayed seasonal variation and were stable in storage. METHODS: Plasma active MMP-9 and TIMP-1 were measured at three time-points in 163 individuals. RESULT: There was no evidence for seasonal variation or declining levels for up to three years of storage at -80°C. CONCLUSION: Active MMP-9 and TIMP-1 appear to be stable seasonally, and in storage for at least three years.

Identical pattern of cerebral hypoperfusion during different types of syncope.

Syncope is caused by insufficient oxygen supply to the brain. There have been attempts to classify syncope on the basis of defects in the venous system, arterial system (that is impaired systemic vascular resistance) or a combination of the two (that is mixed). We examined the hypothesis that a comparable decrease in cerebral perfusion would be evident at pre-syncope irrespective of the category of dysfunction. Young healthy volunteers (N=37) participated. The protocol consisted of 15 min supine rest, followed by 60 degrees head-up tilt and lower body suction in increments of -10 mm Hg for 5 min each until pre-syncope. Beat-to-beat blood pressure (BP) (Finometer or intra-arterial), cardiac output (Finometer), middle cerebral artery blood velocity (MCAv), end-tidal CO(2) and cerebral oxygenation were monitored continuously. At pre-syncope, mixed dysfunction was common (21 out of 37 participants), followed by venular dysfunction (15 out of 37 participants). In the venular and mixed groups, comparable orthostatic tolerance and declines in BP (-37 vs -43% from baseline, respectively), end-tidal PCO(2), MCAv (-35 vs -38%) and cerebral oxygenation (-5 vs -7%) were evident despite distinct mechanisms purportedly being responsible for the hypotension. Although different determinants of hypotension do exist, cerebral hypoperfusion occurs to a similar extent.

Active matrix metalloproteinases 3 and 9 are independently associated with coronary artery in-stent restenosis.

OBJECTIVE: This study aimed to determine whether plasma levels of active matrix metalloproteinases (MMP) are predictors of in-stent restenosis (ISR) in New Zealand patients treated with bare-metal coronary stents. METHODS: A group of 152 patients with a history of ISR were compared with 151 symptom free 1-year post-stenting patients (non-ISR). Demographic and angiographic characteristics were collected. Plasma samples were analyzed for the active forms of MMP-1, -2, -3 and -9 as well as tissue inhibitor of metalloproteinases (TIMP-1) using ELISA-based isoform sensitive assays. RESULTS: Both active MMP-9 and active MMP-3 were independently associated with history of ISR. Elevated levels of both active MMP-3 and -9 had an adjusted odds ratio of 11.8 (95% CI: 4-35, p<0.0001) for association with ISR, with 37% of ISR patients having such levels versus 11% on non-ISR. The addition of both of the MMP biomarkers significantly increased the area under the curve (AUC) of a receiver operator characteristic (ROC) analysis incorporating the significant demographic and angiographic variables (AUC 0.85 versus 0.78, p<0.005). CONCLUSION: Measures of plasma active MMP isoforms appear to be independently associated with ISR, and assessment of multiple MMP markers yields cumulative utility.

Novel rare mutations and promoter haplotypes in ABCA1 contribute to low-HDL-C levels.

The ATP-binding cassette A1 (ABCA1) protein regulates plasma high-density lipoprotein (HDL) levels. Mutations in ABCA1 can cause HDL deficiency and increase the risk of premature coronary artery disease. Single nucleotide polymorphisms (SNPs) in ABCA1 are associated with variation in plasma HDL levels. We investigated the prevalence of mutations and common SNPs in ABCA1 in 154 low-HDL individuals and 102 high-HDL individuals. Mutations were identified in five of the low-HDL subjects, three having novel variants (I659V, R2004K, and A2028V) and two with a previously identified variant (R1068H). Analysis of four SNPs in the ABCA1 gene promoter (C-564T, G-407C, G-278C, and C-14T) identified the C-14T SNP and the TCCT haplotype to be over-represented in low-HDL individuals. The R1587K SNP was over-represented in low-HDL individuals, and the V825I and I883M SNPs over-represented in high-HDL individuals. We conclude that sequence variation in ABCA1 contributes significantly to variation in HDL levels.

Elevated plasma active matrix metalloproteinase-9 level is associated with coronary artery in-stent restenosis.

OBJECTIVE: This study aimed to determine whether the plasma levels of matrix metalloproteinase-9 (MMP-9) or tissue inhibitor of metalloproteinases-1 (TIMP-1) were altered in patients with a history of symptomatic in-stent restenosis (ISR). METHODS AND RESULTS: A group of 158 patients with a history of ISR were compared with 128 symptom-free patients. Plasma samples and a detailed risk factor history were collected. Plasma samples were analyzed for pro-MMP-9 and latent MMP-9 and active MMP-9, latent MMP-3, and TIMP-1. Several variables were associated with ISR, including index coronary disease extent and severity (number of diseased vessels and American College of Cardiology/American Heart Association lesion classification), number, diameter, and total length of stent(s) inserted, and plasma high-density lipoprotein cholesterol. Plasma active MMP-9 (odds ratio, 1.96; 95% CI, 1.43 to 2.69) showed independent risk association with ISR. Patients with multiple sites of ISR had significantly higher levels of active MMP-9 compared with patients with only a single ISR lesion or no ISR. CONCLUSIONS: Plasma active MMP-9 levels may be a useful independent predictor of bare metal stent ISR.

Breast feeding is related to C reactive protein concentration in adult women.

OBJECTIVE: To assess the influence of infant breast feeding on C reactive protein (CRP), a marker of low grade inflammation associated with cardiovascular mortality independent of serum cholesterol concentrations. DESIGN: Serum CRP, total cholesterol, anthropometric, and blood pressure measurements were performed along with assessment of infant breast feeding duration, birth weight, smoking status, adult socioeconomic status, number of health problems, and hormonal contraceptive use. SETTING: A New Zealand predominantly European descent community birth cohort. PARTICIPANTS: 822 men and women aged 26 years. MAIN RESULTS: There was a significant linear relation (p<0.001) between duration of breast feeding and adult CRP level in women. The geometric means (IQR) for CRP were 2.22 (1, 4) mg/l for women breast fed for six months or more and 3.95 (2, 8) mg/l for women not breast fed (ratio, 95% confidence interval (CI): 0.69 (0.55 to 0.87). The linear association between cholesterol and breast feeding was also significant (p = 0.01), the geometric mean (IQR) total cholesterol levels being 4.62 (4.10, 5.10) for those breast fed for six months or more and 5.04 (4.5, 5.80) for those not breast fed (ratio, 95% CI: 0.92 (0.87, 0.98). There was no relation between CRP or total cholesterol and duration of breast feeding in men. CONCLUSIONS: The findings of lower CRP with an increased duration of breast feeding in women suggest early postnatal nutrition may influence long term cardiovascular risk.

Association between C-reactive protein, metabolic cardiovascular risk factors, obesity and oral contraceptive use in young adults.

OBJECTIVE: This study sought to determine the relationship between levels of the inflammatory marker, C-reactive protein (CRP), cardiovascular risk factors and oral contraceptive use in young adults. DESIGN: Cross-sectional study of a community cohort. SUBJECTS: A total of 822 men and women aged 26 y. MEASUREMENTS: CRP, body mass index (BMI), blood pressure, lipid and lipoprotein levels, smoking status, socioeconomic status, health status, and hormonal contraceptive use in women. RESULTS: Multiple regression analysis showed that obesity was independently related to CRP with an increase in ratio CRP of 1.03 (95% CI 1.01, 1.05) for men and 1.07 (1.05, 1.09) for women associated with a 1 kg/m(2) increase in BMI. In women, combined oral contraceptive use was associated with a ratio change in CRP of 1.52 (1.27, 1.82) compared with nonusers. Other independent determinants of CRP in men and women were apolipoprotein B level, systolic blood pressure and apolipoprotein A1 in men. Univariate analysis showed that the relationship between CRP and BMI, systolic blood pressure and apolipoprotein B was significantly stronger in women than men. CONCLUSION: These findings suggest that obesity is associated with inflammation independent of other cardiovascular risk factors that may contribute to an increased risk for cardiovascular disease in men and women. Elevated CRP related to combined oral contraceptive use may influence the rate of cardiovascular events in young women.

Effects of white and red wine on endothelial function in subjects with coronary artery disease.

BACKGROUND: Levels of anti-oxidant polyphenols are higher in red than in white wine and are thought to contribute to the reduced cardiovascular risk associated with moderate consumption of wine observed in epidemiological studies. AIM: To compare the acute effects of acute ingestion of white and red wine on endothelial function in subjects with coronary artery disease (CAD). METHODS: Fourteen subjects with proven CAD were randomised to consume white and red wine with a light meal in a single blind cross-over study. Flow-mediated dilatation (FMD) of the brachial artery was measured using high-resolution ultrasonography. Endothelial function, lipid profile, plasma alcohol and polyphenols were measured at baseline, 60 and 360 min after wine consumption. RESULTS: At baseline, FMD was similar (white wine 1.6 +/- 1.9%, red wine 1.8 +/- 1.7%). At 360 min after ingestion of wine there was no difference in FMD, which improved nearly threefold after both wines (white wine 4.7 +/- 2.2%, red wine 3.4 +/- 2.9%; P = 0.002). There was no detectable change in plasma polyphenol levels after either wine. CONCLUSIONS: These data suggest that wine acutely improves endothelial function in patients with CAD. This improved endothelial function might contribute to a reduced risk of cardiovascular events.