G.P. Tarr

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.

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.

Do high risk patients alter their lifestyle to reduce risk of colorectal cancer

BackgroundColorectal cancer (CRC) may be reduced by healthy lifestyle behaviours. We determined the extent of self-reported lifestyle changes in people at increased risk of CRC, and the association of these reports with anxiety, risk and knowledge-based variables.MethodsWe randomly selected 250 participants who had undergone surveillance colonoscopy for family history of CRC. A telephone interview was conducted, recording demographics and family history. Self-reported lifestyle change due to thoughts about CRC across a range of dietary and lifestyle variables was assessed on a four-point scale. Participants’ perceptions of the following were recorded: risk factor knowledge, personal risk, and worry due to family history. General anxiety was assessed using the GAD-7 scale. Ordinal logistic regression was used to calculate adjusted results.ResultsThere were 148 participants (69% response). 79.7% reported at least one healthy change. Change in diet and physical activity were most frequently reported (fiber, 63%; fruit and vegetables, 54%; red meat, 47%; physical activity, 45%), with consumption of tobacco, alcohol, and body weight less likely (tobacco, 25%; alcohol, 26%; weight 31%). People were more likely to report healthy change with lower levels of generalized anxiety, higher worry due to family history, or greater perceived knowledge of CRC risk factors. Risk perception and risk due to family history were not associated with healthy changes.ConclusionsSelf-reported lifestyle changes due to thoughts about CRC were common. Lower general anxiety levels, worries due to family history, and perceived knowledge of risk factors may stimulate healthy changes.

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.

Erythromelalgia? A Clinical Study of People Who Experience Red, Hot, Painful Feet in the Community

We recruited a population of people who clinically suffer from the symptoms of erythromelalgia, red, hot, painful feet made worse by heat and improved by cooling, to better characterise this population and measure their quality of life (QOL). Ninety-two individuals completed the QOL surveys, and 56 individuals were clinically assessed. There was a 3 : 1 ratio of females to males with an average age of 61 years. The estimated prevalence of people who had clinical symptoms of erythromelalgia in the Dunedin community was 15/100,000. Only 27% of people had received a diagnosis for their symptoms despite seeking medical attention. People in the study population had worse quality of life than the general New Zealand population (P < 0.001). In the majority of participants symptoms had a mild-moderate effect on their quality of life. The results of this study indicate that the number of people who have clinical symptoms of erythromelalgia is much greater than is commonly accepted and that the majority of these individuals go unrecognised by the medical profession despite seeking help. They have significantly diminished QOL with the majority of people having mild-to-moderate symptoms.

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.