TRPV1 antagonists that cause hypothermia, instead of hyperthermia, in rodents: Compounds' pharmacological profiles, in vivo targets, thermoeffectors recruited and implications for drug development.

AIM: Thermoregulatory side effects hinder the development of transient receptor potential vanilloid-1 (TRPV1) antagonists as new painkillers. While many antagonists cause hyperthermia, a well-studied effect, some cause hypothermia. The mechanisms of this hypothermia are unknown and were studied herein. METHODS: Two hypothermia-inducing TRPV1 antagonists, the newly synthesized A-1165901 and the known AMG7905, were used in physiological experiments in rats and mice. Their pharmacological profiles against rat TRPV1 were studied in vitro. RESULTS: Administered peripherally, A-1165901 caused hypothermia in rats by either triggering tail-skin vasodilation (at thermoneutrality) or inhibiting thermogenesis (in the cold). A-1165901-induced hypothermia did not occur in rats with desensitized (by an intraperitoneal dose of the TRPV1 agonist resiniferatoxin) sensory abdominal nerves. The hypothermic responses to A-1165901 and AMG7905 (administered intragastrically or intraperitoneally) were absent in Trpv1-/- mice, even though both compounds evoked pronounced hypothermia in Trpv1+/+ mice. In vitro, both A-1165901 and AMG7905 potently potentiated TRPV1 activation by protons, while potently blocking channel activation by capsaicin. CONCLUSION: TRPV1 antagonists cause hypothermia by an on-target action: on TRPV1 channels on abdominal sensory nerves. These channels are tonically activated by protons and drive the reflectory inhibition of thermogenesis and tail-skin vasoconstriction. Those TRPV1 antagonists that cause hypothermia further inhibit these cold defences, thus decreasing body temperature. SIGNIFICANCE: TRPV1 antagonists (of capsaicin activation) are highly unusual in that they can cause both hyper- and hypothermia by modulating the same mechanism. For drug development, this means that both side effects can be dealt with simultaneously, by minimizing these compounds' interference with TRPV1 activation by protons.

Sample selection may bias the outcome of an adolescent mental health survey: results from a five-year follow-up of 4171 adolescents.

OBJECTIVES: The representativeness of the data is one of the main issues in evaluating the significance of research findings. Dropping out is common in adolescent mental health research, and may distort the results. Nevertheless, very little is known about the types of systematic bias that may affect studies in a) the informed consent phase and b) later in follow-up phases. STUDY DESIGN: The authors addressed this gap in knowledge in a five-year follow-up study on a sample of adolescents aged 13-18 years. METHODS: The data were collected using self-report questionnaires. The baseline sample consisted of 4171 adolescents, 1827 (43.8%) of whom gave consent to be contacted for a follow-up survey, but only 797 (19.1%) participated in the follow-up. Binary logistic regression models were used to explain the participation. RESULTS: Young age, female gender, a high number of hobbies, good performance at school in the native language and general subjects, family disintegration such as divorce, high parental employment, and symptoms of depression and anxiety were associated with both consent and participation. However, the effect of mental health aspects was smaller than the effect of age and gender. CONCLUSIONS: This study confirmed the possibility of systematic selection bias by adolescents' sociodemographic characteristics. The representativeness of the study sample might have been improved by more intense recruitment strategies.

Fear of childbirth in nulliparous and multiparous women: a population-based analysis of all singleton births in Finland in 1997-2010.

OBJECTIVE: To identify risk factors for fear of childbirth (FOC) according to parity and socioeconomic status, and to evaluate associations between FOC and adverse perinatal outcomes. DESIGN: A cohort study. SETTING: The Finnish Medical Birth Register. POPULATION: All 788 317 singleton births during 1997-2010 in Finland. METHODS: Fear of childbirth was defined according to the International Classification of Diseases code O99.80, and its associations with several risk factors and perinatal outcomes were analysed by multivariable logistic regression. MAIN OUTCOME MEASURES: Prevalence of, risk factors for and outcomes of FOC. RESULTS: Fear of childbirth was experienced by 2.5% of nulliparous women and 4.5% of multiparous women. The strongest risk factors for FOC in nulliparous women were depression [adjusted odds ratio (aOR), 6.35; 95% confidence interval (CI), 5.25-7.68], advanced maternal age (aOR, 3.78; 95% CI, 3.23-4.42) and high or unspecified socioeconomic status. In multiparous women, the strongest risk factors for FOC were depression (aOR, 5.47; 95% CI, 4.67-6.41), previous caesarean section (CS) (aOR, 3.02; 95% CI, 2.93-3.11) and high or unspecified socioeconomic status. Among both nulliparous and multiparous women, FOC was associated with higher rates of CS (3.3-fold and 4.5-fold higher, respectively) and a lower incidence of low birthweight (<2500 g), small for gestational age babies, preterm birth and low Apgar scores at 1 minute. CONCLUSIONS: High and unspecified socioeconomic status, advanced maternal age and depression are predisposing factors for FOC regardless of parity. Among multiparous women, a previous CS increases vulnerability to FOC. FOC is associated with increased rates of CS, but does not adversely affect other pregnancy outcomes.

The effect of long-term life dissatisfaction on health-related quality of life among general population subjects.

The aim of this population-based study (n = 329) was to explore how long-term life dissatisfaction (LS burden) and concurrent life dissatisfaction are associated with the concurrent health-related quality of life (HRQL) (RAND-36), and how long-term life dissatisfaction predicts HRQL in the general population. The sum of the life satisfaction scores in 1998, 1999, 2001 (LS burden) and the concurrent life satisfaction score (LS) in 2005 were used to categorize the study participants into satisfied, intermediate and dissatisfied groups. Differences in RAND-36 dimensions in 2005 were investigated with respect to the LS burden and concurrent life dissatisfaction. The predictive power of the LS burden for HRQL dimensions was assessed with logistic regression models. Both a high LS burden and concurrent life dissatisfaction were strongly associated with HRQL and were risk factors for poor HRQL, regardless of its dimensions. The LS burden predicted all of the RAND-36 dimensions, except for physical functioning. Screening of life dissatisfaction can be used to identify service users whose HRQL should be further investigated. Assessment of HRQL provides information on the domains and factors that require mental health nursing intervention. This knowledge could assist mental health nurses in both the alleviation of disease consequences and promotion of well-being of service users.

Proteinuria modifies the effect of systolic blood pressure on total and cardiovascular disease mortality in patients with type 2 diabetes.

OBJECTIVES: Hypertension and proteinuria are major risk factors for cardiovascular disease (CVD) mortality in patients with type 2 diabetes. Blood pressure (BP) targets have been progressively lowered in these patients to prevent or delay the progression of nephropathy. However, no long-term population-based studies have been reported on the interaction between BP and proteinuria with respect to total and CVD mortality in patients with type 2 diabetes. DESIGN: We prospectively followed 881 middle-aged type 2 diabetic patients, free of CVD events at baseline, for up to 18 years. Participants were categorized into four groups according to baseline systolic BP (<130, 130-139, 140-159 and ≥160 mmHg) and further stratified by proteinuria (≤150 or >150 mg L(-1)). Cox proportional hazards model was used to estimate the joint association between systolic BP and proteinuria and the risk of mortality. RESULTS: During follow-up, 607 patients died including 395 because of CVD. After adjustment for confounding factors, total and CVD mortality were significantly higher in patients with proteinuria and systolic BP <130 mmHg compared with those with systolic BP between 130 and 160 mmHg. The prognosis was similar in patients with systolic BP <130 mmHg or ≥160 mmHg. Among patients without proteinuria, systolic BP <130 mmHg was associated with a nonsignificant reduction in mortality. CONCLUSIONS: Type 2 diabetic patients with proteinuria and with systolic BP <130 mmHg may have an increased risk of CVD mortality. The presence of proteinuria should be taken into account when defining the target systolic BP level for the prevention of fatal CVD events in patients with type 2 diabetes.

How does lifestyle intervention affect depressive symptoms? Results from the Finnish Diabetes Prevention Study.

AIMS: To assess the effect of lifestyle intervention on depressive symptoms during a 36-month randomized clinical trial designed to prevent Type 2 diabetes. METHODS: A total of 522 middle-aged participants, who were overweight or obese and had impaired glucose tolerance, were randomized to the lifestyle intervention or control group in the Finnish Diabetes Prevention Study. The intervention group received individualized counselling aimed at reducing weight and increasing physical activity. Depressive symptoms were measured using the Beck Depression Inventory among a subgroup of 140 participants. RESULTS: On study entry, the mean Beck Depression Inventory scores ± sd were 6.8 ± 5.6 in the intervention group and 6.7 ± 5.5 in the control group. Beck Depression Inventory scores reduced during the intervention study: the mean ± sd (95% CI) reduction was 0.90 ± 4.54 (-1.99 to -0.19) scores in the intervention group and 0.75 ± 4.47 (-1.80 to 0.31) in the control group, with no difference between the groups. In a stepwise linear multivariate regression analysis, the variables with the strongest associations with the change in Beck Depression Inventory scores were baseline Beck Depression Inventory scores, marital status, weight change and change of total energy intake (R(2) = 0.209, P < 0.001). CONCLUSIONS: Participation in the study lowered depression scores, with no specific group effect. Among the lifestyle changes, particularly successful reduction of body weight was associated with the greater reduction of depressive symptoms. Thus, regardless of the intensity of the treatment, the success in executing alterations in one's lifestyle and behaviour is associated with beneficial changes in mood.

Proteinuria modifies the effects of physical activity on total and cardiovascular disease mortality rates in patients with type 2 diabetes.

AIMS/HYPOTHESIS: Physical activity reduces cardiovascular disease (CVD) and total mortality rates in patients with type 2 diabetes. However, it is not known whether or not the effects of physical activity on mortality rates depend on the presence of proteinuria in type 2 diabetic patients. METHODS: We prospectively followed up 577 patients with type 2 diabetes who were aged 45 to 64 years and were free of CVD at baseline. Participants were stratified according to the presence of proteinuria (300 mg/l) and the degree of physical activity (0-4 metabolic equivalent tasks [MET] or >4 MET). The Cox proportional hazards model was used to estimate the association of physical activity and proteinuria with risk of mortality. RESULTS: During the 18-year follow-up, 356 patients died, of whom 217 died from CVD. Physically more active patients had significantly reduced total, CVD and CHD mortality rates if they did not have proteinuria. In contrast, physically active proteinuric patients had significantly increased total and CVD mortality rates (HR 1.83, 95% CI 1.00-3.36, p=0.049) in univariate analyses, with HR 2.43 (95% CI 1.09-5.40, p=0.030) in multivariate analyses. CONCLUSIONS/INTERPRETATION: Physical activity reduces total and CVD mortality rates in type 2 diabetic patients without proteinuria. However, in proteinuric patients, no protective effect was observed. Larger studies are needed to confirm the latter finding and to define which exercise intensity leads to possible harmful effects.

Serum adiponectin and resistin levels in major depressive disorder.

OBJECTIVE: To examine the role of the adipose-tissue-derived low-grade inflammation markers adiponectin and resistin in major depressive disorder (MDD) in a population-based sample. METHOD: Serum levels of adiponectin and resistin were measured from 70 DSM-IV MDD subjects and 70 healthy controls. Depression severity was assessed with the 29-item Hamilton Depression Rating Scale. RESULTS: The MDD group had lowered serum adiponectin levels. Regression modelling with adjustments for age, gender, overweight, several socioeconomic and lifestyle factors, coronary heart disease and metabolic syndrome showed that each 5.0 microg/ml decrease in serum adiponectin increased the likelihood of MDD by approximately 20% (P = 0.01). The resistin levels correlated with atypical (P = 0.02), but not with typical depressive symptoms (P = 0.12). CONCLUSION: Our findings suggest that the lowered adiponectin levels in MDD are depression-specific and not explained by conventional low adiponectin-related factors such as such as coronary heart disease and metabolic disorders.

Link between plasma ceramides, inflammation and insulin resistance: association with serum IL-6 concentration in patients with coronary heart disease.

AIMS/HYPOTHESIS: Ceramides and IL-6 have a role in immune-inflammatory responses and cardiovascular diseases, and are suggested to be involved in insulin and glucose metabolism. We sought to assess the associations of circulating levels of IL-6, TNF-alpha and high-sensitivity C reactive protein (hsCRP), which are inflammatory markers related to insulin resistance (IR), with the plasma lipid metabolites ceramides and diacylglycerols (DAG) in patients with CHD. METHODS: Cross-sectional analyses were carried out on data from 33 patients with CHD. Serum levels of the inflammatory markers and plasma lipid metabolites (lipidomics approach performed by ultra-performance liquid chromatography coupled to electrospray ionisation MS) were measured at the same time point as insulin resistance (IR) (HOMA-IR index). RESULTS: Serum circulating levels of IL-6 were strongly correlated with plasma ceramide concentrations (r = 0.59, p < 0.001). Adjustments for serum TNF-alpha or hsCRP levels, smoking, BMI, age, sex or HOMA-IR did not change the results (p < 0.001). After adjustments for the effect of serum inflammatory markers (TNF-alpha or hsCRP), HOMA-IR and BMI the correlation between plasma DAG and serum IL-6 (r = 0.33) was also significant (p < 0.03). In a linear regression model, circulating levels of both ceramides and TNF-alpha had a significant independent influence on circulating levels of IL-6, altogether accounting for 41% of its variation (p < 0.001). CONCLUSIONS/INTERPRETATION: Our results strongly suggest that the link between ceramides, IR and inflammation is related to the inflammatory marker IL-6. Ceramides may contribute to the induction of inflammation involved in IR states that frequently coexist with CHD.

Association of depressive symptoms and metabolic syndrome in men.

OBJECTIVE: To explore the relationship between several indicators of depression and metabolic syndrome (MetS). METHOD: A population-based sample with high (HMS group) or low (LMS group) levels of mental symptoms, including those of depression, in three follow-ups participated in a clinical examination in 2005 (n = 223). MetS was determined according to the NCEP criteria. RESULTS: The prevalence of MetS was 49% in men and 21% in women. Men with MetS had higher rates of major depressive disorder than other men. They also displayed higher Hamilton Rating Scale for Depression (HDRS) scores and more often signs of suicidality. In logistic regression analyses, higher HDRS scores (OR 1.31, 95% CI 1.04-1.64) and belonging to the HMS group (OR 10.1, 95% CI 1.98-51.3) were independent associates for MetS but only in men. CONCLUSION: The results highlight that there is an association between long-term depressive symptoms and the emergence of MetS, especially in men.

Long-term prognosis after coronary artery bypass surgery.

OBJECTIVE: To analyse the risk of coronary heart disease (CHD) events and total mortality among patients who had coronary artery bypass graft (CABG) surgery during 1988-1992. METHODS: A population-based myocardial infarction (MI) register included data on invasive cardiac procedures among residents of the study area. The subjects aged 35-64 years were followed-up for 12 years for non-fatal and fatal CHD events and all-cause mortality, excluding events within 30 days of the CABG operation. CABG was performed on 1158 men and 215 women. RESULTS: The overall survival of men who underwent CABG was similar to the survival of the corresponding background population for about ten years but started to worsen after that. At twelve years of follow-up, 23% (n=266, 95% CI 234-298) of the men who had undergone the operation had died, while the expected proportion, based on mortality in the background population, was 20% (n=231, 95% CI 226-237). The CHD mortality of men who had undergone the operation was clearly higher than in the background population. Among women, the mortality after CABG was about twice the expected mortality in the corresponding background population. In Cox proportional hazards models age, smoking, history of MI, body mass index and diabetes were significant predictors of mortality. CONCLUSIONS: The prognosis of male CABG patients did not differ from the prognosis of the corresponding background population for about ten years, but started to deteriorate after that. History of MI prior to CABG and major cardiovascular risk factors was a predictor of an adverse outcome.

Increased serum levels of advanced glycation endproducts predict total, cardiovascular and coronary mortality in women with type 2 diabetes: a population-based 18 year follow-up study.

AIMS/HYPOTHESIS: AGEs, modification products formed by glycation or glycoxidation of proteins and lipids, have been linked to premature atherosclerosis in patients with diabetes. We investigated whether increased serum levels of AGEs predict total, cardiovascular (CVD) or CHD mortality in a population-based study. SUBJECTS AND METHODS: Serum levels of AGEs were determined by immunoassay in a random sample of 874 Finnish diabetic study participants (488 men, 386 women), aged 45-64 years. These participants were followed for 18 years for total, CVD and CHD mortality. RESULTS: Multivariate Cox regression models revealed that serum levels of AGEs were significantly associated with total (p = 0.002) and CVD mortality (p = 0.021) in women, but not in men. Serum levels of AGEs in the highest sex-specific quartile predicted all-cause (hazards ratio [HR] 1.51; 95% confidence intervals [CI], 1.14-1.99; p = 0.004), CVD (HR 1.56; 95% CI 1.12-2.19; p = 0.009), and CHD (HR 1.68; 95% CI 1.11-2.52; p = 0.013) mortality in women, even after adjustment for confounding factors, including high-sensitivity C-reactive protein. CONCLUSIONS/INTERPRETATION: Increased serum levels of AGEs predict total and CVD mortality in women with type 2 diabetes.

Blockade of mGluR1 receptor results in analgesia and disruption of motor and cognitive performances: effects of A-841720, a novel non-competitive mGluR1 receptor antagonist.

BACKGROUND AND PURPOSE: To further assess the clinical potential of the blockade of metabotropic glutamate receptors (mGluR1) for the treatment of pain. EXPERIMENTAL APPROACH: We characterized the effects of A-841720, a novel, potent and non-competitive mGluR1 antagonist in models of pain and of motor and cognitive function. KEY RESULTS: At recombinant human and native rat mGluR1 receptors, A-841720 inhibited agonist-induced calcium mobilization, with IC50 values of 10.7+/-3.9 and 1.0 +/- 0.2 nM, respectively, while showing selectivity over other mGluR receptors, in addition to other neurotransmitter receptors, ion channels, and transporters. Intraperitoneal injection of A-841720 potently reduced complete Freund's adjuvant-induced inflammatory pain (ED50 = 23 micromol kg(-1)) and monoiodoacetate-induced joint pain (ED50 = 43 micromol kg(-1)). A-841720 also decreased mechanical allodynia observed in both the sciatic nerve chronic constriction injury and L5-L6 spinal nerve ligation (SNL) models of neuropathic pain (ED50 = 28 and 27 micromol kg(-1), respectively). Electrophysiological studies demonstrated that systemic administration of A-841720 in SNL animals significantly reduced evoked firing in spinal wide dynamic range neurons. Significant motor side effects were observed at analgesic doses and A-841720 also impaired cognitive function in the Y-maze and the Water Maze tests. CONCLUSIONS AND IMPLICATIONS: The analgesic effects of a selective mGluR1 receptor antagonist are associated with motor and cognitive side effects. The lack of separation between efficacy and side effects in pre-clinical models indicates that mGluR1 antagonism may not provide an adequate therapeutic window for the development of such antagonists as novel analgesic agents in humans.

Multi-technique characterization of a nuclear bomb particle from the Palomares accident.

A January 1966 accident dispersed Pu and other nuclear bomb materials in the vicinity of Palomares, a village in southeastern Spain. Radioactive particles were identified in a soil sample collected in 1998 and analytical results obtained from one of the isolated particles are presented here. Isolation of the particle was performed using gamma-ray spectrometry and imaging plates. Scanning electron microscopy with X-ray microanalysis revealed the presence of U and Pu as well as Pb and Fe in the particle of approximately 10microm diameter. Radioisotopes of U, Pu, and Am were quantified using radiometric methods, inductively coupled plasma mass spectrometry and secondary ion mass spectrometry. The elevated (235)U/(238)U atom ratio indicates enriched U, and the Pu atom ratios are consistent with weapons-grade material. This work demonstrates that the analysis of individual particles provides information not available through bulk sample analysis.

Proteinuria and metabolic syndrome as predictors of cardiovascular death in non-diabetic and type 2 diabetic men and women.

AIMS/HYPOTHESIS: Proteinuria predicts cardiovascular disease (CVD), but it is unclear whether this is explained by the association of the metabolic syndrome with proteinuria. Therefore, we investigated proteinuria and the metabolic syndrome as independent predictors of CVD death in men and women. METHODS: The cohort comprised 574 non-diabetic men, 707 non-diabetic women, 371 diabetic men and 349 diabetic women, all free of CVD at baseline. Modified World Health Organization criteria were used to define the metabolic syndrome, and a urinary protein concentration of >or=0.1 g/l (or >or=0.2 g/l) to define proteinuria. The endpoint was CVD mortality during the 18-year follow-up. RESULTS: Among non-diabetic men, CVD mortality per 1,000 person-years was as follows: no metabolic syndrome, no urinary protein group: 5.3; no metabolic syndrome, positive for urinary protein: 8.9; positive for metabolic syndrome, no urinary protein: 13.3; and positive for metabolic syndrome and urinary protein: 14.9. For non-diabetic women the corresponding values were: 0.9, 2.3, 4.9 and 7.9, respectively. Among diabetic men, CVD mortality per 1,000 person-years was 15.2, 32.5, 23.6 and 42.0 for the respective groups. Among diabetic women it was 25.3, 38.0, 26.3 and 40.3 (urinary protein in all cases defined as >or=0.1 g/l). In multivariate Cox models including both urinary protein and metabolic syndrome, the hazard ratios (HRs, 95% CI) of proteinuria for CVD mortality were 1.5 (0.9-2.4) in non-diabetic men, 1.8 (0.8-4.2) in non-diabetic women, 1.6 (1.0-2.6) in diabetic men and 1.6 (1.1-2.3) in diabetic women. Urinary protein as a continuous variable was associated with CVD mortality in all groups. The corresponding HRs for metabolic syndrome were: 1.6 (0.9-2.7), 4.0 (1.7-9.7), 1.5 (1.1-2.0) and 1.1 (0.8-1.5). CONCLUSIONS/INTERPRETATION: Proteinuria predicted CVD mortality independently of the presence of metabolic syndrome in non-diabetic and diabetic subjects. Metabolic syndrome predicted CVD mortality in non-diabetic women and in diabetic men, independently of the presence of proteinuria.

Myocardial infarction in diabetic and non-diabetic persons with and without prior myocardial infarction: the FINAMI Study.

AIMS/HYPOTHESIS: We compared the risk of acute coronary events in diabetic and non-diabetic persons with and without prior myocardial infarction (MI), stratified by age and sex. METHODS: A Finnish MI-register study known as FINAMI recorded incident MIs and coronary deaths (n=6988) among people aged 45 to 74 years in four areas of Finland between 1993 and 2002. The population-based FINRISK surveys were used to estimate the numbers of persons with prior diabetes and prior MI in the population. RESULTS: Persons with diabetes but no prior MI and persons with prior MI but no diabetes had a markedly greater risk of a coronary event than persons without diabetes and without prior MI. The rate of recurrent MI among non-diabetic men with prior MI was higher than the incidence of first MI among diabetic men aged 45 to 54 years. The rate ratio was 2.14 (95% CI 1.40-3.27) among men aged 50. Among elderly men, diabetes conferred a higher risk than prior MI. Diabetic women had a similar risk of suffering a first MI as non-diabetic women with a prior MI had for suffering a recurrent MI. CONCLUSIONS/INTERPRETATION: Both persons with diabetes but no prior MI, and persons with a prior MI but no diabetes are high-risk individuals. Among men, a prior MI conferred a higher risk of a coronary event than diabetes in the 45-54 year age group, but the situation was reversed in the elderly. Among diabetic women, the risk of suffering a first MI was similar to the risk that non-diabetic women with prior MI had of suffering a recurrent MI.

Five-year risk of developing clinical diabetes after first myocardial infarction; the FINAMI study.

AIM: To investigate the incidence of clinical diabetes as determined by the incidence of diabetes drug reimbursements within a 5-year period after the first myocardial infarction (MI) in patients who were non-diabetic at the time of their first MI. RESEARCH DESIGN AND METHODS: A population-based MI register, FINMONICA/FINAMI, recorded all coronary events in persons of 35-64 years of age between 1988 and 2002 in four study areas in Finland. These records were used to identify subjects sustaining their first MI (n = 2632). Participants of the population-based risk factor survey FINRISK (surveys 1987, 1992, 1997 and 2002), who did not have diabetes or a history of MI, served as the control group (n = 7774). The FINMONICA/FINAMI study records were linked with the National Social Security Institute's drug reimbursement records, which include diabetes medications, using personal identification codes. The records were used to identify subjects who developed diabetes during the 5-year follow-up period (n = 98 in the MI group and n = 79 in the control group). RESULTS: Sixteen per cent of men and 20% of women sustaining their first MI were known to have diabetes and thus were excluded from this analysis. Non-diabetic men having a first MI were at more than twofold {hazard ratio (HR) 2.3 [95% confidence interval (CI) 1.6-3.4]}, and women fourfold [HR 4.3 (95% CI 2.4-7.5)], risk of developing diabetes mellitus during the next 5 years compared with the control population without MI. CONCLUSIONS: Many patients who do not have diabetes at the time of their first MI develop diabetes in the following 5 years.

Risk factor management in diabetic and non-diabetic patients with coronary heart disease. Findings from the EUROASPIRE I AND II surveys.

AIMS/HYPOTHESIS: We examined risk factor management in diabetic and non-diabetic patients with CHD based on data from EUROASPIRE surveys. METHODS: Consecutive CHD patients aged 70 years or younger were interviewed and examined at least 6 months after hospitalisation for a revascularisation procedure or acute myocardial infarction or ischaemia. Of these patients, 3569 were from the EUROASPIRE I study, undertaken from 1995 to 1996 in nine countries, and 5556 were from the EUROASPIRE II study, conducted between 1999 and 2000 in 15 countries. RESULTS: In EUROASPIRE I and II 18% and 20% of CHD patients respectively had been previously diagnosed with diabetes. Fasting glucose screening raised the prevalence of diabetes in EUROASPIRE II to 28%. In EUROSPIRE II the prevalence of risk factors (known diabetic/non-diabetic) was: current smoking 17%/22 % ( p=0.25); obesity (BMI >/=30 kg/m(2)) 43%/29% ( p<0.001); raised blood pressure (>/=140/90 mm Hg) 57%/49% ( p<0.001); and elevated total cholesterol (>/=5.0 mmol/l) 55%/59% ( p<0.001). The proportion of users of cardiovascular medication was: antiplatelet drugs 83%/86% (NS); beta-blockers 62%/63% (NS); ACE inhibitors 49%/35% ( p<0.001); and lipid-lowering drugs 62%/61% (NS). A comparison of both studies showed that for diabetic and non-diabetic patients the prevalence of smoking had increased somewhat and that the prevalence of obesity had increased clearly. There was no improvement in blood pressure control, but cholesterol control had improved, mainly explained by the increased use of lipid-lowering drugs. CONCLUSIONS/INTERPRETATION: These European surveys show a high prevalence of adverse lifestyles and modifiable risk factors among diabetic and non-diabetic patients with CHD. The risk factor status was more adverse in diabetic patients.