Plasma CD93 concentration is a potential novel biomarker for coronary artery disease.

OBJECTIVES: A common nonsynonymous single nucleotide polymorphism (SNP) in the CD93 gene (rs3746731, Pro541Ser) has been associated with risk of coronary artery disease (CAD). CD93 is a transmembrane glycoprotein, which is detectable in soluble form in human plasma. We investigated whether the concentration of soluble CD93 in plasma is related to risk of myocardial infarction (MI) and CAD, using a case-control study of premature MI (n = 764) and a nested case-control analysis of a longitudinal cohort study of 60-year-old subjects (analysis comprising 844 of 4232 subjects enrolled at baseline). In addition, SNPs in the CD93 gene were studied in relation to plasma CD93 concentration and CD93 mRNA expression. METHODS AND RESULTS: A sensitive and specific enzyme-linked immunosorbent assay was established for determination of the plasma CD93 concentration. Subjects were divided into three groups according to tertiles of the distribution of CD93 concentration. Lower odds ratios for risk of MI and incidence of CAD were observed in the middle CD93 tertile (142-173 µg L(-1) ): odds ratio (95% confidence interval), 0.69 (0.49-0.97) and 0.61 (0.40-0.94), respectively. These associations were independent of traditional CAD risk factors. The minor allele of a SNP in the 3' untranslated region of CD93 (rs2749812) was associated with increased plasma CD93 concentrations (P = 0.03) and increased CD93 mRNA expression levels (P = 0.02). CONCLUSION: The results of the present study suggest that the concentration of soluble CD93 in plasma is a potential novel biomarker for CAD, including MI.

Low Psychological General Well-Being (PGWB) is associated with deteriorated 10-year survival in men but not in women among the elderly.

We studied Psychological General Well-Being (PGWB) and its relation to 10-year survival in 75-year-olds from the general population. The PGWB global score (sum of six subscale scores) and the subscale scores were transformed to 0-100 scales. Ten-year survival in relation to PGWB global and subscale scores was studied in a cohort of 204 men and 213 women. Global PGWB score (median) was 83 in men and 79 in women (for difference p=0.001). Significantly higher male scores were found for most PGWB subscales. Global PGWB score was significantly related to better 10-year survival in men (relative risk per ten points of score was 0.80; p=0.001 and 0.85; p=0.022 adjusting for chronic diseases and living alone) but not in women (relative risk 0.94; p=0.478 unadjusted). Among 75-year-olds, PGWB score was significantly higher for men. A high PGWB score was significantly related to better survival in men but not in women.

Mannose-binding lectin genotype and phenotype in patients with type 2 diabetes and myocardial infarction: a report from the DIGAMI 2 trial.

OBJECTIVE: The present study characterizes mannose-binding lectin (MBL), an activator of the complement system and thereby important for inflammatory activation, in patients with diabetes and myocardial infarction. RESEARCH DESIGN AND METHODS: Serum (S)-MBL was determined at hospital admission in 387 patients with type 2 diabetes (median age 70 years; 68% male) with myocardial infarction, and genotyping was performed in 287 patients. Cardiovascular events (cardiovascular mortality and nonfatal myocardial infarction or stroke) were recorded during 2.5 years. RESULTS: Median S-MBL was 1,212 µg/l (interquartile range [IQR] 346-2,681 µg/l). Of the subjects, 54% in the geno- and phenotype subgroup had a high-coding MBL genotype (median S-MBL=2,658 µg/l [IQR 1,715-3,829]) and 46% a low-coding MBL genotype (373 µg/l [100-765]). S-MBL did not correlate with age, BMI, creatinine clearance, glucose, or A1C. Cardiovascular events occurred in 136 (35%) patients. S-MBL did not predict events in univariable analyses (hazard ratio 0.93 [95% CI 0.85-1.01]; P=0.09). In unadjusted analyses, the risk of events was lower in patients with a high genotype and S-MBL above the median for their genotype (0.49 [0.26-0.92]; P=0.026) than for patients with a low genotype and S-MBL below the median for their genotype. The prediction capacity of the geno- and phenotype model was of borderline significance in adjusted Cox regression. CONCLUSIONS: Patients with type 2 diabetes and myocardial infarction have MBL genotypes that are similar to those known in the general population. The combination of a low-coding MBL genotype with a low S-MBL appears to be prognostically unfavorable, but the association is blunted by traditional risk markers.

Insulin-induced weight gain and cardiovascular events in patients with type 2 diabetes. A report from the DIGAMI 2 study.

AIM: We investigated whether insulin treatment-induced weight gain was accompanied by increased cardiovascular (CV) mortality and morbidity in the second Diabetes Insulin Glucose in Acute Myocardial Infarction (DIGAMI 2) study. METHODS: We studied the 865 patients who survived during 12 months without any change in their glucose-lowering (GL) therapy. They were divided into four subgroups according to GL treatment: group I, no pharmacological GL treatment (n = 99); group II, oral hypoglycaemic agents (n = 250); group III, new insulin treatment (n = 245) and group IV, insulin before inclusion continued during the first year of follow up (n = 271). RESULTS: Patients who started on insulin (group III) experienced an average body weight increase of 2.3 (1.5-3.2) kg during the first year of treatment, whereas weight remained unchanged in groups I, II and IV. The incidence of non-fatal reinfarction was higher in group III compared with the other groups (hazard ratio (HR) = 2.5, p = 0.011) and CV mortality was higher in group IV (HR = 2.4, p = 0.003). When the subjects were grouped in quartiles according to maximal body weight increase, those in the lowest quartile experienced the highest CV mortality. Each kilogram increase in weight reduced the risk for CV death with 6%. The incidence of reinfarction did not differ between quartiles. CONCLUSIONS: Initiation of insulin treatment after myocardial infarction was associated with a significant increase in weight and incidence of reinfarction. The increase in weight did, however, not explain the increased rate of reinfarction.

Augmented blood pressure response to exercise is associated with improved long-term survival in older people.

OBJECTIVE: Studies on the prognostic importance of the systolic blood pressure (SBP) response during exercise report ambiguous results. Most research focuses on younger and middle-aged selected patient groups and rarely includes women. We investigated the prognostic value of SBP response during exercise testing in 75-year-olds. DESIGN: Prospective observational cohort study. SETTING: A community-based random sample of 75-year-old men and women (n = 382). MAIN OUTCOME MEASURES: The prognostic value of SBP change from rest to peak exercise during a symptom-limited cycle test was evaluated for the endpoints all-cause mortality and cardiovascular mortality during long-term follow-up. RESULTS: After a median follow-up of 10.6 years, 140 (37%) of the participants had died, 64 (17%) from cardiovascular causes. The all-cause mortalities for exercise SBP changes of < or =30 mm Hg, 31-55 mm Hg and >55 mm Hg were 5.1, 4.2 and 2.6 per 100 person-years, respectively (logrank 9.6; p = 0.008). For every 10 mm Hg increase in SBP during exercise the relative hazard for all-cause mortality was reduced by 13% (p = 0.030) and for cardiovascular mortality by 26% (p = 0.004) after adjustment for sex, smoking, waist circumference, total/HDL cholesterol ratio, prevalent ischaemic heart disease, hypertension, diabetes, cardiovascular medication, pre-exercise SBP, exercise capacity, resting left ventricular ejection fraction and left ventricular mass index. CONCLUSIONS: Our findings suggest that an augmented SBP response during exercise is associated with an improved long-term survival among community-living 75-year-old individuals.

Genetic variants of TNFSF4 and risk for carotid artery disease and stroke.

In two independent human cohorts, the minor allele of SNP rs3850641 in TNFSF4 was significantly more frequent in individuals with myocardial infarction than in controls. In mice, Tnfsf4 expression is associated with increased atherosclerosis. The expression of TNFSF4 in human atherosclerosis and the association between genotype and cerebrovascular disease have not yet been investigated. TNFSF4 messenger RNA (mRNA) levels were significantly higher in human atherosclerotic lesions compared with controls (730 +/- 30 vs 330 +/- 65 arbitrary units, p < 0.01). TNFSF4 was mainly expressed by macrophages in atherosclerotic lesions. In cell culture, endothelial cells upregulated TNFSF4 in response to tumor necrosis factor alpha (TNF-alpha; 460 +/- 110 vs 133 +/- 8 arbitrary units, p < 0.001 after 6 h of stimulation). We analyzed the TNFSF4 gene in 239 patients who had undergone carotid endarterectomy and 138 matching controls from The Biobank of Karolinska Carotid Endarterectomies and Stockholm Heart Epidemiology Program cohorts and 929 patients and 1,382 matching controls from the Sahlgrenska Academy Study on Ischemic Stroke and Case Control Study of Stroke cohorts, limiting inclusion to patients with ischemic stroke. Participants were genotyped for the rs3850641 SNP in TNFSF4. Genotype associations were neither found with TNFSF4 mRNA levels nor with atherosclerosis associated systemic factors or risk for stroke. This study shows that TNFSF4 is expressed on antigen-presenting cells in human carotid atherosclerotic lesions but provides no evidence for an association of TNFSF4 gene variation with the risk for ischemic stroke.

Insulin glargine improves glycaemic control after coronary surgery in patients with diabetes or pre-diabetes.

OBJECTIVES: Determine if pre-emptive daily insulin glargine surpasses regular insulin when needed for glycaemic control after cardiac surgery. DESIGN: Prospective, randomized study of 43 patients (scheduled for coronary artery bypass grafting) with preoperatively diagnosed diabetes (DM) or pre-DM. Lantus group received insulin glargine daily from start of surgery while Actrapid group received regular insulin (sliding scale) when needed (plasma glucose (P-glu)>10 mmol/l). Primary endpoint was percent of pre- and post-prandial P-glu values within Target Intervals: Pre-prandial P-glu: 4.5-7 mmol/l; post-prandial P-glu: 4.5-9 mmol/l. Study period 1-4 days after surgery. Tissue glucose was also measured continuously. RESULTS: More than twice as many P-glu values were within Target Interval for Lantus patients as compared with Actrapid patients (p<0.001). One of 504 timed measurements was <4 mmol/l. Area under the curve for glucose>7 mmol/l was reduced by 61% by Lantus (p<0.001). CONCLUSION: The routine protocol with pre-emptive glargine insulin studied here provides a major improvement in glycaemic control with a minimal incidence of hypoglycaemia and without an excessive increase in nursing burden.

Do psychosocial factors predict disability and health at a 3-year follow-up for patients with non-acute musculoskeletal pain? A validation of the Orebro Musculoskeletal Pain Screening Questionnaire.

PURPOSE: Early identification and intervention with those that run the risk of developing long-term disability would offer a great opportunity for reducing costs and personal suffering associated with long-term work absenteeism. The Orebro Musculoskeletal Pain Screening Questionnaire (OMPSQ) has been used and validated in several studies for participants with mainly acute pain problems. The aim of this study was to validate the OMPSQ for patients with non-acute pain problems (e.g. 1-6 months sick leave) and compare to other relevant questionnaires. METHOD: One hundred and fifty-eight patients with musculoskeletal pain and disability recruited to a multidisciplinary rehabilitation project completed a battery of questionnaires at baseline and at 3-year follow-up visits. The main analysis involved the relationship between risk levels in the questionnaire and sick leave and perceived health after 3 years. RESULTS: The OMSPQ predicted future sick leave and health and was found to have six factors. The function and pain factors were the best predictors of sick leave after 3 years, while the distress factor was the best predictor of perceived mental health and return to work-expectancy was borderline significant. Perceived physical health at 3 years was best predicted by the function and pain factors with the fear-avoidance factor being marginally significant. CONCLUSION: The results demonstrate that psychosocial factors as measured by OMPSQ are related to work disability and perceived health even 3 years after treatment for patients with non-acute pain problems. The OMSPQ was a good predictor of outcome.

Oral glucose tolerance test is needed for appropriate classification of glucose regulation in patients with coronary artery disease: a report from the Euro Heart Survey on Diabetes and the Heart.

BACKGROUND: Patients with coronary artery disease (CAD) and abnormal glucose regulation (AGR) are at high risk for subsequent cardiovascular events, underlining the importance of accurate glucometabolic assessment in clinical practice. OBJECTIVE: To investigate different methods to identify glucose disturbances among patients with acute and stable coronary heart disease. METHODS: Consecutive patients referred to cardiologists were prospectively enrolled at 110 centres in 25 countries (n = 4961). Fasting plasma glucose (FPG) and glycaemia 2 h after a 75-g glucose load were requested in patients without known glucose abnormalities (n = 3362). Glucose metabolism was classified according to the World Health Organization and American Diabetes Association (ADA; 1997, 2004) criteria as normal, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or diabetes. RESULTS: Data on FPG and 2-h post-load glycaemia were available for 1867 patients, of whom 870 (47%) had normal glucose regulation, 87 (5%) had IFG, 591 (32%) had IGT and 319 (17%) had diabetes. If classification had been based on the ADA criterion from 1997, the proportion of misclassified (underdiagnosed) patients would have been 39%. The ADA 2004 criterion would have overdiagnosed 8% and underdiagnosed 33% of the patients, resulting in a total misclassification rate of 41%. For ethical concerns and practical reasons, oral glucose tolerance test (OGTT) was not conducted in 1495 of eligible patients. These patients were more often women, had higher age and waist circumference, and were therefore more likely to have AGR than those who were included. A model based on easily available clinical and laboratory variables, including FPG, high-density lipoprotein cholesterol, age and the logarithm of glycated haemoglobin A1c, misclassified 44% of the patients, of whom 18% were overdiagnosed and 26% were underdiagnosed. CONCLUSION: An OGTT is still the most appropriate method for the clinical assessment of glucometabolic status in patients with coronary heart disease.

White blood cell counts associate more strongly to the metabolic syndrome in 75-year-old women than in men: a population based study.

BACKGROUND: A positive relation between the metabolic syndrome (MetS) and inflammatory activity has been reported. The purpose of this investigation was to study the relationships between 1) white blood cell (WBC) count and MetS, 2) WBC count and the individual components of MetS and 3) WBC count and insulin sensitivity in 75-year-old women and men from the general population. METHODS: The study included 200 women and 196 men comprising 64% of the 75-year old people from the city of Västerås in Sweden. MetS was defined according to the National Cholesterol Education Program (NCEP). RESULTS: WBC count (10(9)/L; median and interquartile range) was 5.7 (4.9-6.8) for women and 6.3 (5.4-7.2) for men, P < .001 for gender difference. For women with and without MetS, WBC count was 6.3 (5.3-7.3) and 5.4(4.7-6.3), respectively. For men the corresponding figures were 6.7 (5.9-7.6) and 6.1 (5.4-7.1).The difference in WBC count between individuals with and without MetS was significant (P < .001 for women; P = .014 for men). All individual components of MetS (with exception of blood pressure) were more strongly associated with WBC count for women than for men. Insulin sensitivity, measured as HOMA-IR (HOmeostasis Model Assessment-Insulin Resistance) index, was significantly associated with WBC count in women but not in men. CONCLUSIONS: In this elderly population, individuals with MetS had a higher WBC count than those without. Women had a lower WBC count and stronger relationship between WBC count and insulin sensitivity than did men.

Insulin-like growth factor I: a predictor of long-term glucose abnormalities in patients with acute myocardial infarction.

AIMS/HYPOTHESIS: Low levels of IGF-I are associated with increased risk of cardiovascular disease and type 2 diabetes. The aim of this study was to investigate the IGF-I system in patients with acute myocardial infarction (AMI) without previously known diabetes. MATERIALS AND METHODS: One hundred and sixty-eight AMI patients were classified before hospital discharge by means of an OGTT as having NGT, IGT or newly detected type 2 diabetes. Age- and sex-matched subjects from the background population (n=185) served as the control group. The associations between fasting levels of IGF-I and IGF binding proteins 1 and 3 (IGFBP-1, IGFBP-3) and glucose metabolism during a follow-up period of 12 months were studied. RESULTS: At hospital discharge, age-adjusted IGF-I (IGF-I SD) was significantly lower in patients with abnormal glucose tolerance (AGT=IGT or type 2 diabetes) compared with patients with NGT (p=0.014) and control subjects (p<0.001). IGF-I was strongly correlated with IGFBP-3 (r=0.730, p<0.001), which was significantly lower in patients with AGT compared with patients with NGT (p=0.009) and control subjects (p<0.001). Fasting levels of IGFBP-1 did not differ significantly between patients with NGT and AGT or between patients and control subjects. In a multiple logistic regression analysis in patients, IGF-I at hospital discharge was a significant predictor of AGT at discharge and after 12 months (adjusted odds ratio 0.29, p=0.022, and adjusted odds ratio 0.29, p=0.034, respectively). CONCLUSIONS/INTERPRETATION: Low levels of IGF-I may be a useful predictor of abnormal glucose metabolism in patients with AMI.

Distension of painful structures in the treatment for chronic pelvic pain in women.

BACKGROUND: There is a lack of established treatment for Chronic pelvic pain (CPP), defined as acyclic pain of at least six months duration. We decided to study the pain-alleviating effects of stretching on defined structures in women with CPP, and the treatment's impact on quality of life variables. DESIGN OF STUDY: An open, randomized study. SETTING: Primary Health Care Centre, Kolbäck, Sweden. METHODS: Fifty women, median age 33 years (range 19-54), complaining of CPP for a median duration of 25.5 months (range 6-264) were randomly assigned to either a treatment or a control group. A short questionnaire containing 17 questions was administered before randomization and two to three weeks after a second treatment of distension of pelvic structures. Visual analog scales were used for questions concerning intensity of pain and quality of life. Five-point scales were used for questions dealing with duration and frequency of pain. RESULTS: Intensity, frequency and duration of pelvic pain, painful intercourse, lower back pain, sleep disturbance, sleep quality, mental fatigue, depression, mood and anger improved significantly more in the treatment group than in the control group. Treatment proved more effective than counseling as reflected by self-rating scales: pain intensity (OR 18.37, 95% CI 3.39-99.64) and pain during intercourse (OR 8.59, 95% CI 1.57-46.68). CONCLUSION: In this open, randomized study, distension of painful pelvic structures in women with CPP resulted in significant relief of pain and improvement in quality of life measures.

QTc interval and survival in 75-year-old men and women from the general population.

AIMS: The study concerns the relationship of the corrected QT (QTc) interval to 6.4 years of survival and to measures of cardiac function, such as echocardiographic variables and plasma levels of brain natriuretic peptide (BNP), in 75-year-old people. METHODS AND RESULTS: QTc was measured in a 12-lead electrocardiogram (ECG) in 210 men and 223 women, comprising a randomly selected sample from the general population (70% participation rate). The Sicard 440/740 computer-analysis program, with Hodges' formula for heart rate-based QT correction, was used. The optimal cut-off point for predicting survival according to the receiver operating characteristic curve was found between 429 and 430 ms. Individuals with a QTc interval of > or =430 ms (n = 115) had decreased survival when compared with those with shorter QTc interval (n = 318); the relative risk was 2.4 (95% confidence interval 1.5-3.7). The predictive ability of QTc reflects an association between QTc and the following variables: BNP, left ventricular mass, and left ventricular ejection fraction (but not diastolic filling patterns). Both Hodges' and Bazett's formulae for heart rate correction of the QT interval were useful for predicting survival. The median QTc was 415 ms using Hodges' formula and 430 ms with Bazett's formula. The QRS component of QTc predicted survival better than the rest of the QTc interval and was approximately as useful as the QTc interval itself. CONCLUSION: The computer-derived QTc obtained from the ordinary 12-lead ECG identifies high-risk individuals among elderly people from the general population.

Quality of life and maintenance of improvements after early multimodal rehabilitation: a 5-year follow-up.

PURPOSE: There is a paucity of long-term evaluations on rehabilitation of musculoskeletal disorders, e.g., neck, shoulder or back pain. The aim of this study was to assess quality of life and the effect of early multimodal rehabilitation on 91 patients with musculoskeletal pain and disability at a 5-year follow-up. METHOD: The follow-up assessment, which included questions on pain, function, quality of life, perceived health, sick leave and psychosomatic symptoms, was performed 5 years after the assessment of baseline status. RESULTS: Improvements in pain, perceived health and psychosomatic symptoms were maintained at the 5-year follow-up. In addition, improvements in function, quality of life, and level of acceptable pain were significant in comparison to baseline. At the time of the baseline assessment all patients were on sick leave (13% were on partial sick leave). At the 5-year follow-up, 58% of the patients were at work part or full time. The results show that those working differed significantly from those not working at the 5-year follow-up on almost all variables, indicating that those working enjoy better health. The most salient prognostic factors for return to work were perceived health and educational level at the time of the baseline evaluation. CONCLUSIONS: These results show that treatment improved quality of life and the effects were basically maintained at 5 years. Work capacity as reflected in return to work increased greatly (81%) at a 1-year follow-up and was substantial (58%) at the 5-year follow-up. Moreover, perceived health and educational levels were important prognostic factors. Finally, the fact that patients working reported better health underscores the probable importance of return to work. Our results imply that it may be feasible to obtain long-term benefits from such a primary care-based intervention.

Beta cell dysfunction in patients with acute myocardial infarction but without previously known type 2 diabetes: a report from the GAMI study.

AIMS/HYPOTHESIS: Patients with acute myocardial infarction (AMI) but without previously known type 2 diabetes have a high prevalence of undiagnosed IGT and type 2 diabetes. Such perturbations have dismal prognostic implications. The aim of this study was to characterise AMI patients in terms of insulin resistance and beta cell function. METHODS: A total of 168 consecutive AMI patients were classified by means of an OGTT before hospital discharge as having NGT, IGT or type 2 diabetes. The homeostasis model assessment (HOMA-IR) was used to estimate insulin resistance. Beta cell responsiveness was quantified as insulinogenic index (IGI) at 30 min (DeltaI(30)/DeltaG(30)). RESULTS: According to the HOMA-IR, patients with type 2 diabetes were more insulin resistant than those with IGT or NGT (p=0.003). Beta cell responsiveness deteriorated with decreasing glucose tolerance as measured by the IGI (median [quartile 1, quartile 3] in pmol/mmol: NGT, 70.1 [42.7, 101.4]; IGT, 48.7 [34.7, 86.8], type 2 diabetes, 38.1 [25.7, 61.6]; p<0.001). The IGI was significantly related to admission capillary blood glucose (r=-0.218, p=0.010) and to the area under the curve for glucose (r=-0.475, p<0.001). CONCLUSIONS/INTERPRETATION: Glucose abnormalities are very common in patients with AMI but without previously known type 2 diabetes. To a significant extent, this seems to be related to impaired beta cell function and implies that dysglycaemia immediately after an infarction is not a stress epiphenomenon but reflects stable disturbances of glucose regulation preceding the AMI. Early beta cell dysfunction may have important pathophysiological implications and may serve as a future target for treatment strategies.

Newly detected abnormal glucose tolerance: an important predictor of long-term outcome after myocardial infarction.

AIMS: Recent data revealed that patients with myocardial infarction (MI) have a high prevalence of previously unknown diabetes mellitus (DM) and impaired glucose tolerance (IGT). The added prognostic importance of this finding has not been prospectively explored. To investigate whether a newly detected abnormal glucose tolerance (IGT or DM) assessed early after an MI, is related to long-term prognosis. METHODS AND RESULTS: Patients (n=168; age 63.5+/-9.3 years) with MI, no previous DM and admission blood glucose <11.0 mmol/l were followed for major cardiovascular events defined as the composite of cardiovascular death, non-fatal MI, non-fatal stroke or severe heart failure (HF). According to an oral glucose tolerance test (OGTT) before hospital discharge, 55 patients had normal and 113 abnormal glucose tolerance (GT). During the follow-up of median 34 months there were eight cardiovascular deaths, 15 patients had a recurrent MI, six had a stroke and ten severe HF. All patients who died from cardiovascular causes had abnormal GT. The composite cardiovascular event occurred in 31 (18%) patients. The probability of remaining free from cardiovascular events was significantly higher in patients with normal than abnormal GT (p=0.002). Together with previous MI, abnormal GT was the strongest predictor of future cardiovascular events (hazard ratio 4.18; CI 1.26-13.84; p=0.019). CONCLUSIONS: Abnormal glucose tolerance is a strong risk factor for future cardiovascular events after myocardial infarction. Since it is common and possible to detect even during the hospital phase it may be a target for novel secondary preventive efforts.

Abnormal glucose tolerance--a common risk factor in patients with acute myocardial infarction in comparison with population-based controls.

BACKGROUND: A high prevalence of newly detected diabetes and impaired glucose tolerance (abnormal glucose tolerance) was recently reported in patients with acute myocardial infarction. It is important to verify whether this finding is specific for the patients or attributable to the population, from which they were recruited. OBJECTIVE: To verify whether abnormal glucose tolerance is more prevalent in patients than in controls chosen from the same population and to compare metabolic characteristics between the two groups. DESIGN AND SUBJECTS: The metabolic state was assessed in patients (n = 181) admitted with acute myocardial infarction and no history of diabetes before discharge and after 3 months. Sex- and age-matched controls (n = 185) without previously known diabetes or cardiovascular disease except hypertension were recruited from the general population. MAIN OUTCOME MEASURES: Oral glucose tolerance test, glucosylated haemoglobin A1c (HbA1c), insulin, proinsulin, lipid profile, fibrinolytic function and inflammatory markers. RESULTS: Abnormal glucose tolerance was more common (number/all classified) in patients at discharge 113/168 (67%) and after 3 months 95/145 (66%) than in controls 65/185 (35%) (P < 0.001). Dyslipidaemia (70% vs. 29%; P < 0.001) and previously treated hypertension (32% vs. 18%; P = 0.028) were more frequent amongst patients whilst obesity (18% vs. 24%) did not differ significantly. Blood glucose, HbA1c, proinsulin, proinsulin/insulin ratio, triglycerides, insulin resistance (by HOMA) and fibrinogen were consistently higher in patients than controls (P < 0.01). CONCLUSIONS: Abnormal glucose tolerance was almost twice as common amongst patients with acute myocardial infarction as in matched controls. Impaired glycaemic control accompanied by insulin resistance, dyslipidaemia, hypertension, together with increased plasma fibrinogen and proinsulin levels were main features characterizing patients.

Basal glucometabolic status has an impact on long-term prognosis following an acute myocardial infarction in non-diabetic patients.

OBJECTIVES: Patients with diabetes are known to have a worse prognosis after an acute myocardial infarction (AMI) compared with non-diabetic patients. The primary aim of this study was to investigate the effect of glucometabolic status on long-term prognosis in non-diabetic patients with an AMI. The second aim was to evaluate the extent to which blood glucose levels at admission depended on acute stress, assessed as serum cortisol, previous glucometabolic status, measured as haemoglobin A1c (HbA1c), or both. DESIGN: In a prospective study of patients with an AMI, blood glucose, HbA1c and cortisol were measured at admission. Fasting blood glucose was determined before discharge and also afterwards, if necessary, for classification. Patients were followed-up for 5.5 years. SUBJECTS: Of the 305 consecutive patients 24% were diagnosed as diabetic and 76% as non-diabetic. MAIN OUTCOME MEASURES: Death or non-fatal myocardial re-infarction. RESULTS: In non-diabetic patients, a Cox regression model was used. With death or re-infarction as endpoint, the following prognostic factors had an impact on event-free survival: age (P<0.001), HbA1c (P=0.002), cortisol (P<0.001) and thrombolytic treatment (P=0.001). There was a correlation between cortisol and blood glucose at admission (r=0.44, P<0.001). Fasting blood glucose day 5 showed no association with event-free survival. CONCLUSIONS: In non-diabetic patients with AMI, admission HbA1c and cortisol were predictors for 5.5-year survival without recurrent non-fatal myocardial infarction. The glucometabolic status of importance for prognosis was detected by HbA1c but not by fasting blood glucose or admission blood glucose, of which the latter was influenced by cortisol.

Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease: the result of a meta-analysis.

BACKGROUND: The results of retrospective and prospective case-control studies have clearly established that mild elevations of the plasma homocysteine level are associated with increased risk of coronary, cerebral, and peripheral vascular disease. Recently, a mutation (677C-->T) was identified in the methylenetetrahydrofolate reductase (MTHFR) gene that results in reduced folate-dependent enzyme activity and reduced remethylation of homocysteine to methionine. Mutant homozygotes (TT genotype) constitute approximately 12% of the white population and frequently have mildly elevated circulating homocysteine. Therefore, it seems likely that they would also be at increased risk of vascular disease. A number of studies have investigated this during the past 3 years, and the present article evaluates the results in a meta-analysis. METHODS AND RESULTS: We identified 13 studies in which there were measurements of plasma homocysteine in relation to the 3 genotypes (TT, CT, and CC) and 23 case-control studies comprising 5869 genotyped cardiovascular disease patients (mostly coronary artery disease) and 6644 genotyped control subjects. Those bearing the TT genotype had plasma homocysteine concentrations 2.6 micromol/L (25%) higher than those with the CC genotype. However, there was no difference between patients and control subjects either in the frequency of mutant alleles (T) (34.3% versus 33.8%) or the TT genotype (11.9% versus 11.7%). In the analysis of the 23 studies, the relative risk (OR) of vascular disease associated with the TT genotype was 1.12 (95% CI, 0.92 to 1.37). CONCLUSIONS: We conclude that although the C677T/MTHFR mutation is a major cause of mild hyperhomocysteinemia, the mutation does not increase cardiovascular risk. Our findings suggest that the mild hyperhomocysteinemia found frequently in vascular disease patients is not causally related to the pathogenesis of the vascular disease.

Long-term renal preservation in essential hypertension. Angiotensin converting enzyme inhibition is superior to beta-blockade.

Antihypertensive treatment is known to slow down the decline in glomerular filtration rate (GFR) with time. Angiotensin converting enzyme (ACE) inhibition has been shown to be more effective in this regard than conventional antihypertensive therapy. In a recent prospective, randomized, double blind trial in 257 patients with essential hypertension, the loss of GFR, determined with 51Cr-EDTA clearance, was significantly less with an ACE inhibitor (cilazapril) than with a beta-adrenoceptor blocker (atenolol) during the first year of treatment. However, after 2 years, the two therapies were equally effective in this regard, thereby creating doubts about the long-term superiority of ACE inhibition in this regard. In order to elucidate whether the superior renal preservation with the ACE inhibitor was a transient effect, GFR was measured after 1 more year of treatment, i.e., after 36 months. At that time, the decline in GFR was significantly smaller in the ACE inhibitor group as compared to the beta-adrenoceptor blocker group (-3.0 [-5.5, -1.0; 95% CI] v -7.0 [-9.0, -4.5; 95% CI] mL/min x 1.73 m2; P = .026). This demonstrates that in the treatment of essential hypertension ACE inhibition preserves GFR significantly better than beta-adrenoceptor blockade during long-term therapy.