Directional hydrophone clusters reveal evasive responses of small cetaceans to disturbance during construction at offshore windfarms.

Mitigation measures to disperse marine mammals prior to pile-driving include acoustic deterrent devices and piling soft starts, but their efficacy remains uncertain. We developed a self-contained portable hydrophone cluster to detect small cetacean movements from the distributions of bearings to detections. Using an array of clusters within 10 km of foundation pile installations, we tested the hypothesis that harbour porpoises (Phocoena phocoena) respond to mitigation measures at offshore windfarm sites by moving away. During baseline periods, porpoise movements were evenly distributed in all directions. By contrast, animals showed significant directional movement away from sound sources during acoustic deterrent device use and piling soft starts. We demonstrate that porpoises respond to measures aimed to mitigate the most severe impacts of construction at offshore windfarms by swimming directly away from these sound sources. Portable directional hydrophone clusters now provide opportunities to characterize responses to disturbance sources across a broad suite of habitats and contexts.

Evaluating adaptive co-management as conservation conflict resolution: Learning from seals and salmon.

By linking iterative learning and knowledge generation with power-sharing, adaptive co-management (ACM) provides a potential solution to resolving complex social-ecological problems. In this paper we evaluate ACM as a mechanism for resolving conservation conflict using a case study in Scotland, where seal and salmon fishery stakeholders have opposing and entrenched objectives. ACM emerged in 2002, successfully resolving this long-standing conflict. Applying evaluation approaches from the literature, in 2011 we interviewed stakeholders to characterise the evolution of ACM, and factors associated with its success over 10 years. In common with other ACM cases, triggers for the process were shifts in slow variables controlling the system (seal and salmon abundance, public perceptions of seal shooting), and exogenous shocks (changes in legal mandates, a seal disease outbreak). Also typical of ACM, three phases of evolution were evident: emerging local leadership preparing the system for change, a policy window of opportunity, and stakeholder partnerships building the resilience of the system. Parameters maintaining ACM were legal mechanisms and structures, legal power held by government, and the willingness of all stakeholders to reach a compromise and experiment with an alternative governance approach. Results highlighted the critical role of government power and support in resolving conservation conflict, which may constrain the extent of local stakeholder-driven ACM. The evaluation also demonstrated how, following perceived success, the trajectory of ACM has shifted to a 'stakeholder apathy' phase, with declining leadership, knowledge exchange, stakeholder engagement, and system resilience. We discuss remedial actions required to revive the process, and the importance of long term government resourcing and alternative financing schemes for successful conflict resolution. Based on the results we present a generic indicator framework and participatory method for the longitudinal evaluation of ACM applied to conservation conflict resolution.

The association of fasting plasma sulfur-containing compounds with BMI, serum lipids and apolipoproteins.

BACKGROUND AND AIM: Sulfur amino acids are recognized as potent modulators of lipid metabolism. Plasma total cysteine (tCys) is associated with fat mass, obesity and serum LDL-cholesterol and apolipoprotein (Apo)-B in large population studies. It is not known how fasting plasma concentrations of cysteine precursors and products relate to these associations in humans, given that sulfur-containing compounds (SCC) influence rodent weight gain and serum lipids. METHODS AND RESULTS: We investigated the cross-sectional associations of fasting plasma SCC (methionine, total homocysteine, cystathionine, tCys, taurine and total glutathione) with BMI and fasting serum lipids and apolipoproteins in 854 men and women with and without cardiovascular disease (CVD). In multiple linear regression analysis adjusted for age, gender, CVD and other SCC, neither methionine, taurine, nor total glutathione was associated with BMI. Plasma taurine was, however, inversely related to HDL-cholesterol (partial r = -0.12, p = 0.004) and its associated apoA1 (partial r = -0.18, p < 0.001). Plasma cystathionine correlated positively with triglycerides and BMI, while tCys positively correlated with total cholesterol, LDL-cholesterol (partial r = 0.20, p < 0.001) and its associated apoB. The associations of SCC with serum lipids were independent of BMI. tCys was also independently associated with BMI (partial r = 0.20, p < 0.001) after adjustment for other SCC, glucose, lipids and apolipoproteins. CONCLUSIONS: Fasting tCys is associated with BMI independently of metabolically related SCC. Elevation of plasma SCC is generally associated with an unfavorable lipid profile. The negative relations of plasma taurine with HDL-C and apoA1 deserve further investigation.

Exercise induced fatigue: unfit or unwell?

This case report outlines the diagnoses of a rare myophosphorylase deficiency (McArdle Syndrome) in a unique way. A set of characteristic values from a Cardiopulmonary Exercise Test (CPET) combined with a typical patient history pointed to a failure of the glycolytic pathway in the skeletal muscle. McArdle Syndrome was confirmed with a skeletal muscle biopsy. There is no evidence of such a diagnostic method in the literature.

Homocysteine status and cardiovascular risk factors in patients with psoriasis: a case-control study.

BACKGROUND: Psoriasis is a hyperproliferative, cutaneous disorder with the potential to lower levels of folate. This may result in raised levels of homocysteine, an independent risk factor for the development of cardiovascular disease. OBJECTIVE: A study was conducted to compare levels of red-cell folate (RCF) and homocysteine in patients with psoriasis and in healthy controls. Levels of homocysteine were also examined in the context of other major cardiovascular risk factors. METHODS: In total, 20 patients with psoriasis and 20 controls had their RCF, homo-cysteine and other conventional cardiovascular risk factors assessed. RESULTS: Patients with psoriasis had a trend towards lower levels of RCF. Significantly raised levels of homocysteine were found in patients with psoriasis compared with controls (P = 0.007). There was no correlation between homocysteine levels, RCF levels or disease activity as measured by the Psoriasis Area and Severity Index. Patients with psoriasis had higher body mass index (P < 0.004) and higher systolic blood pressure (P < 0.001) than controls. This may contribute to the excess cardiovascular mortality observed in patients with psoriasis.

Dyslipidemia therapy update: the importance of full lipid profile assessment.

Lipid guidelines typically focus on total cholesterol +/- low-density lipoprotein cholesterol levels with less emphasis on high-density lipoprotein cholesterol (HDL-C) or triglyceride assessment, thus potentially underestimating cardiovascular (CV) risk and the need for lifestyle or treatment optimization. In this article, we highlight how reliance on isolated total cholesterol assessment may miss prognostically relevant lipid abnormalities; we describe from the European Systematic COronary Risk Evaluation (SCORE) data set how incorporation of HDL-C may improve estimation of CV risk; and, finally, we critically evaluate the evidence base surrounding triglycerides and CV risk.

Bridging science and health policy in cardiovascular disease: focus on lipid management: A Report from a Session held during the 7th International Symposium on Multiple Risk Factors in Cardiovascular Diseases: Prevention and Intervention--Health Policy, in Venice, Italy, on 25 October, 2008.

In Europe, cardiovascular disease (CVD) represents the main cause of morbidity and mortality, costing countries euro 190 billion yearly (2006). CVD prevention remains unsatisfactory across Europe largely due to poor control of CVD risk factors (RFs), growing incidence of obesity and diabetes, and sedentary lifestyle/poor dietary habits. Hypercholesterolaemia is a proven CVD RF, and LDL-C lowering slows atherosclerotic progression and reduces major coronary events. Lipid-lowering therapy is cost-effective, and intensive treatment of high-risk patients further improves cost effectiveness. In Italy, models indicate that improved cholesterol management translates into potential yearly savings of euro 2.9-4 billion. Identifying and eliminating legislative and administrative barriers is essential to providing optimal lipid care to high-risk patients. Public health and government policy can influence clinical practice rapidly, and guideline endorsement via national health policy may reduce the CVD burden and change physician and patient behaviour. Action to reduce CVD burden should ideally include the integration of strategies to lower the incidence of major CV events, improvement in total CV risk estimation, database monitoring of CVD trends, and development of population educational initiatives on CVD prevention. Failure to bridge the gap between science and health policy, particularly in relation to lipid management, could result in missed opportunities to reverse the burgeoning epidemic of CVD in Europe.

HDL cholesterol protects against cardiovascular disease in both genders, at all ages and at all levels of risk.

OBJECTIVE: We aimed to clarify some previous inconsistencies regarding the role of high density lipoprotein cholesterol (HDL-C) as a CVD protective factor. METHODS: The SCORE dataset contained data on HDL-C for 104,961 individuals (45% women) without pre-existing coronary heart disease (CHD). These were from 7 pooled European prospective studies. The effect of HDL-C, both in quintiles and as a continuous variable, on risk of CVD and CHD mortality was examined, using Cox proportional hazards model, adjusted for age, total cholesterol, systolic blood pressure, smoking, diabetes and body mass index and stratified by gender, age group, country and category of SCORE CVD risk. RESULTS: A strong, graded, independent, inverse relationship between HDL-C and both CVD and CHD mortality was demonstrated. Adjusted hazard ratios per 0.5mmol/l increase in HDL-C were 0.60 (0.51, 0.69) and 0.76 (0.70, 0.83) in women and men, respectively for the CVD mortality endpoint. The corresponding hazard ratios were 0.53 (0.42, 0.68) and 0.79 (0.64, 0.98) in elderly women and men, respectively. The relationship was significant in all SCORE CVD risk strata and age groups. CONCLUSIONS: This multivariable analysis, the largest of its kind to date, has confirmed the inverse, independent, strong and graded relationship between HDL-C and both CVD and CHD mortality. We have clarified previous suggestions that the relationship is stronger in women and that it applies in all age groups. This is the first prospective study to demonstrate the independent relationship specifically in healthy elderly women and to show that the relationship holds at all levels of total CVD risk.

Chest pain and hypertension in an 18 year old girl.

We describe the case of an 18 year old lady who presented with chest pain, breathlessness and hypertension. The initial diagnosis of renal artery stenosis, while correct, was incomplete. The finding of a reduced right radial pulse suggested the possibility of a large vessel vasculitis. She was also found to have critical coronary artery disease that required stenting and aortic incompetence. Renal artery stenting was also performed. Additional investigations confirmed Takayasu's arteritis. With immunosuppressive therapy and stenting she is now well and normotensive but may require aortic valve replacement in the future.

Survey of medication documentation at hospital discharge: implications for patient safety and continuity of care.

BACKGROUND: Medication discrepancies at the time of hospital discharge are common and can result in error, patient/carer inconvenience or patient harm. Providing accurate medication information to the next care provider is necessary to prevent adverse events. AIMS: To investigate the quality and consistency of medication details generated for such transfer from an Irish teaching hospital. METHODS: This was an observational study of 139 cardiology patients admitted over a 3 month period during which a pharmacist prospectively recorded details of medication inconsistencies. RESULTS: A discrepancy in medication documentation at discharge occurred in 10.8% of medication orders, affecting 65.5% of patients. While patient harm was assessed, it was only felt necessary to contact three (2%) patients. The most common inconsistency was drug omission (20.9%). CONCLUSIONS: Inaccuracy of medication information at hospital discharge is common and compromises quality of care.

Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project.

AIMS: The SCORE project was initiated to develop a risk scoring system for use in the clinical management of cardiovascular risk in European clinical practice. METHODS AND RESULTS: The project assembled a pool of datasets from 12 European cohort studies, mainly carried out in general population settings. There were 20,5178 persons (88,080 women and 11,7098 men) representing 2.7 million person years of follow-up. There were 7934 cardiovascular deaths, of which 5652 were deaths from coronary heart disease. Ten-year risk of fatal cardiovascular disease was calculated using a Weibull model in which age was used as a measure of exposure time to risk rather than as a risk factor. Separate estimation equations were calculated for coronary heart disease and for non-coronary cardiovascular disease. These were calculated for high-risk and low-risk regions of Europe. Two parallel estimation models were developed, one based on total cholesterol and the other on total cholesterol/HDL cholesterol ratio. The risk estimations are displayed graphically in simple risk charts. Predictive value of the risk charts was examined by applying them to persons aged 45-64; areas under ROC curves ranged from 0.71 to 0.84. CONCLUSIONS: The SCORE risk estimation system offers direct estimation of total fatal cardiovascular risk in a format suited to the constraints of clinical practice.

Plasma total cysteine as a risk factor for vascular disease: The European Concerted Action Project.

BACKGROUND: Elevated plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease. Although cysteine is structurally similar and metabolically linked to tHcy, its relation to the risk of cardiovascular disease has received little attention. We studied the relation between plasma total cysteine (tCys) levels and the risk of vascular disease in the coronary, cerebral, and peripheral vessels. METHODS AND RESULTS: This case-control study included 750 patients with vascular disease and 800 age- and sex-matched control subjects recruited from 19 centers in 9 European countries. Conventional risk factors for cardiovascular disease were recorded. In addition, plasma levels of tCys, tHcy, folate, B(6), B(12), and creatinine were measured. Overall, a U-shaped relationship was observed between tCys and risk of vascular disease. With the middle range of 250 to 275 micromol/L tCys used as the reference category, the adjusted risk of vascular disease at low (300 micromol/L) tCys levels was 1.6 (95% CI 1.1 to 2.3). Different shapes of the dose-response relationship were seen for the 3 vascular disease categories. The relation with peripheral vascular and cerebrovascular disease was U-shaped, whereas a weak positive relation was observed with coronary heart disease. CONCLUSIONS: Our data show a significant U-shaped relationship between tCys and cardiovascular disease after adjustment for tHcy, creatinine, and other cardiovascular disease risk factors.

Thermolabile MTHFR genotype and retinal vascular occlusive disease.

BACKGROUND: Raised levels of total plasma homocysteine (tHcy) are associated with an increased risk of retinal vascular occlusive disease. A thermolabile form of a pivotal enzyme in homocysteine metabolism, methylenetetrahydrofolate reductase (MTHFR), has been associated with vascular occlusive disease and raised tHcy levels. The relation between thermolabile MTHFR genotype, tHcy, and retinal vascular occlusive disease has not been determined. METHODS: A retrospective case-control study involving hospital based controls and cases with retinal vascular occlusions in whom tHcy levels had been determined was undertaken. Genotyping for the MTHFR 677 C-T mutation that specifies the thermolabile form of the enzyme was performed by established methods in all subjects. The relation between homozygosity for thermolabile MTHFR genotype (TT), raised tHcy levels, and risk of retinal vascular occlusive disease was examined. RESULTS: 87 cases of retinal vascular occlusive disease (mean age 68.7 years) comprising 26 cases of retinal artery occlusion and 61 of retinal vein occlusion were compared with 87 controls (mean age 70.2 years). The TT genotype did not confer a significantly increased risk of retinal vascular occlusive disease. The mean tHcy level was significantly higher in the cases than in the controls (p<0.0001). Overall, and in both the cases and controls, the frequency of the TT genotype was higher in those with normal tHcy levels than in those with increased levels of tHcy. However, the TT genotype did not significantly alter the risk of increased tHcy levels in these patients. CONCLUSIONS: The TT genotype is not associated with an increased risk of retinal vascular occlusive disease or increased tHcy levels in this group of elderly patients. In older patients, nutritional rather than genetic factors may be more important in increasing tHcy levels, a known risk factor for retinal vascular occlusive disease.

The role of folic acid in the prevention of cardiovascular disease.

Coronary heart disease is the leading cause of death in the developed world. Current surgical and pharmacological interventions are essentially palliative and interest in preventive strategies, particularly through nutrition and avoidance of tobacco has increased in recent years. Basic scientific, clinical and epidemiological evidence indicates a positive association between the plasma level of the amino acid homocysteine and vascular disease. Homocysteine levels are inversely related to both intake and plasma levels of folate. Less strong evidence indicates an inverse relationship between folate intake and coronary heart disease risk. It is likely that current estimates of dietary folate requirements are lower than optimal. Folic acid supplementation reliably reduces homocysteine levels, and may also modify endothelial function independent of this effect on homocysteine. Such treatment is cheap and appears to be essentially free of risk. However, until present randomised control trials are complete, it will not be known definitively whether or not increasing folate intake reduces cardiovascular risk.

Effect of plasma homocysteine concentration on early and late events in patients with acute coronary syndromes.

BACKGROUND: Although a raised plasma homocysteine is a risk factor for vascular disease, it is not known whether it is associated with an adverse cardiac outcome in patients admitted with acute coronary syndromes. We evaluated the relationship between plasma homocysteine and short-term (28 days) and long-term (median 2.5 years) prognosis in acute coronary syndromes. METHODS AND RESULTS: We evaluated the relationship of quintiles of homocysteine to fatal and nonfatal coronary disease early (28 days) and late (29 days to a median of 2. 5 years) after admission to a single unit of patients with unstable angina (n=204) and myocardial infarction (n=236). The end points studied were cardiac death (n=67) and/or myocardial (re)infarction (n=30). Cox regression and logistic regression were used to estimate the relationship of homocysteine to coronary events. The event rate within the first 28 days (22 cardiac deaths and 5 nonfatal infarctions) was not related to the admission homocysteine level. In the 203 unstable angina and 214 myocardial infarction survivors, an apparent threshold effect was seen on long-term follow-up, with a significant step-up in the frequency of events between the lowest 3 quintiles (14 cardiac deaths and 11 nonfatal infarctions) and the upper 2 quintiles (31 fatal and 12 nonfatal events). Patients in the upper 2 quintiles (>12.2 micromol/L) had a 2.6-fold increase in the risk of a cardiac event (95% CI, 1.5 to 4.3, P<0.001). CONCLUSIONS: Elevated total homocysteine levels on admission strongly predict late cardiac events in acute coronary syndromes.

Homocysteine, vitamin status and risk of vascular disease; effects of gender and menopausal status. European COMAC Group.

BACKGROUND: Elevated plasma total homocysteine (tHcy) is a known risk factor for vascular disease. Gender, age, and circulating levels of folate, vitamins B(6)and B(12)affect tHcy levels. Objectives To study associations of gender and age with levels of plasma tHcy, and to examine the relationships of tHcy and circulating levels of folate, vitamins B(6)and B(12)with risk of vascular disease in men and women (pre- and post-menopausal). MATERIAL AND METHODS: In a multicentre case-control study in Europe, 750 patients (544 men, 206 women) with documented vascular disease of the coronary, cerebral, or peripheral vessels and 800 control subjects (570 men, 230 women) were enrolled. Plasma tHcy levels (fasting and after methionine loading) and circulating levels of the vitamins were measured. Adjustment for age and centre was carried out for all statistical analyses, with additional adjustment for serum creatinine and vitamins for the tHcy comparisons between the sexes and between cases and controls. Risk analyses included adjustment for creatinine and traditional risk factors. Relationships between age, gender and tHcy were studied among control subjects only. RESULTS: Fasting tHcy levels were lower in women than in men. Levels of tHcy showed a positive association with age, for both sexes. In the post-menopausal age category, female post-methionine load tHcy levels surpassed levels of men. Elevation of tHcy (defined as >80th percentile of controls) appeared to be at least as strong a risk factor for vascular disease in women as in men, even before the menopause. For post-methionine load tHcy, there was a 40% stronger association with vascular disease in women than in men. In both sexes, but especially in pre-menopausal women, low circulating levels of vitamin B(6)conferred a two- to threefold increased risk of vascular disease, independent of tHcy. In men, but not in women, low (defined as <20th percentile of controls) circulating folate levels were associated with a 50% increased risk of vascular disease. CONCLUSIONS: Elevation of tHcy appears to be at least as strong a risk for vascular disease in women as men, even before the menopause. Our data indicate that associations of the various tHcy measurements (and the vitamins that determine them), with risks of vascular disease may differ between the sexes. The tHcy-independent relationship of vitamin B(6)with vascular disease indicates that it will be advisable to test the effects of vitamin B(6)in clinical trials.

Genetic analysis of the thermolabile variant of 5, 10-methylenetetrahydrofolate reductase as a risk factor for ischemic stroke.

Mild hyperhomocysteinemia is a risk factor for atherosclerotic vascular disease. Homozygosity for the C677T mutation in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR) is frequently associated with hyperhomocysteinemia, particularly in individuals with low levels of serum folate, and has been directly associated with cardiovascular disease in certain populations. The purpose of this study was to establish whether the C677T mutation, which causes thermolabile MTHFR, is a risk factor for ischemic stroke in the Irish population. The homozygous C677T genotype has previously been associated with coronary heart disease in Ireland. We collected blood from 174 individuals (minimum age 60 years) who had suffered an ischemic stroke that was confirmed by computed tomography brain scan. Control subjects (n=183) aged >/=60 years, who had never suffered a stroke or transient ischemic attack, were recruited from hospitals and active retirement groups in the same geographical area. MTHFR genotypes were determined and other known risk factors for stroke were documented. In the control group, the frequency of subjects with the homozygous C677T genotype was 10.4%. In patients who had suffered ischemic stroke, the frequency was 15.5%. This difference was not statistically significant. The odds ratio of stroke for C677T homozygotes, with other genotypes as a reference group, was 1.59, 95% CI=0.85, 2.97. The data indicate that the homozygous C677T MTHFR genotype is at most a moderate risk factor for ischemic stroke.

Homocysteine and vascular disease: nature or nurture?

There is now abundant evidence that elevated plasma total homocysteine is a risk factor for vascular disease in general and for cardiovascular disease in particular. Plasma concentrations of homocysteine are modulated by both genetic and environmental factors, among which inherited enzymatic defects and nutritional deficiencies respectively, are probably the most important. Other environmental factors such as smoking, also influence plasma homocysteine concentrations. The role of nutritional and other environmental factors had been underestimated until recently, when a final examination of the contribution of inherited defects became possible with the advent of DNA isolation and sequencing of large population samples. There is now consistent evidence from many studies that plasma homocysteine levels are inversely correlated with plasma folate, pyridoxal 5'-phosphate and cobalamin levels. This finding, together with that of significant lowering of homocysteine levels achieved with folate supplementation, constitutes a basis for optimism in reducing cardiovascular risk. As yet, no randomised control trial has been carried out to test this hypothesis.

Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project.

CONTEXT: Elevated plasma homocysteine is a known risk factor for atherosclerotic vascular disease, but the strength of the relationship and the interaction of plasma homocysteine with other risk factors are unclear. OBJECTIVE: To establish the magnitude of the vascular disease risk associated with an increased plasma homocysteine level and to examine interaction effects between elevated plasma homocysteine level and conventional risk factors. DESIGN: Case-control study. SETTING: Nineteen centers in 9 European countries. PATIENTS: A total of 750 cases of atherosclerotic vascular disease (cardiac, cerebral, and peripheral) and 800 controls of both sexes younger than 60 years. MEASUREMENTS: Plasma total homocysteine was measured while subjects were fasting and after a standardized methionine-loading test, which involves the administration of 100 mg of methionine per kilogram and stresses the metabolic pathway responsible for the irreversible degradation of homocysteine. Plasma cobalamin, pyridoxal 5'-phosphate, red blood cell folate, serum cholesterol, smoking, and blood pressure were also measured. RESULTS: The relative risk for vascular disease in the top fifth compared with the bottom four fifths of the control fasting total homocysteine distribution was 2.2 (95% confidence interval, 1.6-2.9). Methionine loading identified an additional 27% of at-risk cases. A dose-response effect was noted between total homocysteine level and risk. The risk was similar to and independent of that of other risk factors, but interaction effects were noted between homocysteine and these risk factors; for both sexes combined, an increased fasting homocysteine level showed a more than multiplicative effect on risk in smokers and in hypertensive subjects. Red blood cell folate, cobalamin, and pyridoxal phosphate, all of which modulate homocysteine metabolism, were inversely related to total homocysteine levels. Compared with nonusers of vitamin supplements, the small number of subjects taking such vitamins appeared to have a substantially lower risk of vascular disease, a proportion of which was attributable to lower plasma homocysteine levels. CONCLUSIONS: An increased plasma total homocysteine level confers an independent risk of vascular disease similar to that of smoking or hyperlipidemia. It powerfully increases the risk associated with smoking and hypertension. It is time to undertake randomized controlled trials of the effect of vitamins that reduce plasma homocysteine levels on vascular disease risk.