Long-Term Glycemic Variability and Vascular Complications in Type 2 Diabetes: Post Hoc Analysis of the FIELD Study.

AIMS: To investigate whether long-term glycemic variability (GV) is associated with vascular complication development in type 2 diabetes. METHODS: In a post hoc FIELD trial analysis, GV was calculated as the standard deviation and coefficient of variation (CV) of glycated hemoglobin A1c (HbA1c) and fasting plasma glucose. Baseline variables were compared across quartiles of on-study variability by chi square and ANOVA. Prospective associations between baseline to 2-year GV and subsequent vascular and mortality outcomes were analyzed using landmark logistic and Cox proportional hazards regression. RESULTS: Baseline factors associated with higher on-study GV included younger age, male gender, longer diabetes duration, and higher pharmacological therapies usage. Both HbA1c and fasting glucose CV were associated with increased risk of microvascular complications (HR 1.02 [95% CI, 1.01-1.03] P < 0.01; and HR 1.01 [95% CI, 1.00-1.01] P < 0.001, respectively). HbA1c and fasting glucose CV were associated with increased cardiovascular disease (HR 1.02 [95% CI, 1.00-1.04]; and HR 1.01 [95% CI, 1.00-1.02], both P < 0.05). HbA1c CV associated with increased stroke (HR 1.03 [95% CI, 1.01-1.06) P < 0.01). Glucose CV associated with increased coronary events (HR 1.01 [95% CI, 1.00-1.02] P < 0.05). Both HbA1c and glucose CV associated with increased total mortality (HR 1.04 [95% CI, 1.02-1.06]; and HR 1.01 [95% CI, 1.01-1.02], both P < 0.001) and noncardiovascular mortality (HR 1.05 [95% CI, (1.03-1.07]; and HR 1.02 [95% CI, 1.01-1.03], both P < 0.001). HbA1c CV associated with coronary mortality (HR 1.04 [95% CI, 1.01-1.07] P < 0.05). CONCLUSIONS: Long-term GV was associated with increased risk of vascular outcomes in type 2 diabetes.

SuPAR predicts postoperative complications and mortality in patients with asymptomatic aortic stenosis.

Background: We evaluated whether early measurement of soluble urokinase plasminogen activator receptor (suPAR) could predict future risk of postoperative complications in initially asymptomatic patients with mild-moderate aortic stenosis (AS) undergoing aortic valve replacement (AVR) surgery. Methods: Baseline plasma suPAR levels were available in 411 patients who underwent AVR surgery during follow-up in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Cox analyses were used to evaluate suPAR in relation to all-cause mortality and the composite endpoint of postoperative complications (all-cause mortality, congestive heart failure, stroke and renal impairment) occurring in the 30-day postoperative period. Results: Patients with initially higher levels of suPAR were at increased risk of postoperative mortality with a HR of 3.5 (95% CI 1.4 to 9.0, P=0.008) and postoperative complications with a HR of 2.7 (95% CI 1.5 to 5.1, P=0.002), per doubling in suPAR. After adjusting for the European System for Cardiac Operative Risk Evaluation or Society of Thoracic Surgeons risk score, suPAR remained associated with postoperative mortality with a HR 3.2 (95% CI 1.2 to 8.6, P=0.025) and 2.7 (95% CI 1.0 to 7.8, P=0.061); and postoperative complications with a HR of 2.5 (95% CI 1.3 to 5.0, P=0.007) and 2.4 (95% CI 1.2 to 4.8, P=0.011), respectively. Conclusion: Higher baseline suPAR levels are associated with an increased risk for postoperative complications and mortality in patients with mild-moderate, asymptomatic AS undergoing later AVR surgery. Further validation in other subsets of AS individuals are warranted. Trial registration number: NCT00092677; Post-results.

Ambulatory Blood Pressure Characteristics and Long-Term Risk for Atrial Fibrillation.

BACKGROUND: We hypothesized that elevated nighttime systolic ambulatory blood pressure (ABP) yields additional information compared with daytime systolic ABP for the long-term risk of atrial fibrillation (AF) and perhaps should be taken into account in treatment strategies for preventing the increasing burden of AF during aging. METHODS: A total of 903 subjects with or without hypertension aged 40 to 59 years, who were recruited to the Oulu Project Elucidating Risk of Atherosclerosis (OPERA) study, underwent ABP monitoring, thorough clinical examinations and laboratory tests. RESULTS: After an average of 16.4 ± 3.6 years of follow-up, 91 (10%) of the study subjects had experienced a new-onset AF requiring a hospital emergency room or hospital visit. Of the components of baseline ABP, the nighttime mean systolic blood pressure had the strongest univariable association with the occurrence of AF (120.8 ± 15.9 vs. 116.4 ± 14.1 mm Hg, P = 0.006, in subjects with vs. without the occurrence AF). When the univariable predictors of AF, such as age, sex, body mass index, height, smoking history, alanine aminotransferase, uric acid, and fasting plasma glucose, were entered in the multivariable Cox hazards model, age (P < 0.001), and body mass index (P = 0.014) retained their significant predictive power. After adjustments in this clinical hazards model, the nighttime mean systolic blood pressure still predicted the occurrence of AF (hazards ratio = 1.07 per every 5 mm Hg increase, 95% confidence intervals = 1.004-1.15, P = 0.038). CONCLUSION: Of the baseline ABP characteristics, the nighttime systolic blood pressure is a significant independent contributor to the long-term risk of new-onset AF requiring a hospital visit.

[Prevention of arterial diseases in the 2010s: the European treatment guideline]. / Valtimosairauksien ehkäisy 2010-luvulla: eurooppalainen hoitosuositus.

Reduction of risk factors at the population level forms the basis of the European recommendation of 2012 for the prevention of arterial diseases. Actions at the individual level arise from risk assessment. The risk of arterial disease is graded into four categories, the uppermost ones comprising patients who have already developed the disease, diabetics, those suffering from renal insufficiency and those carrying a serious gene defect. In Finland the risk among healthy people is assessed by using the FINRISKI tool. Non-smoking, healthy diet and regular exercise are suitable for all. Statins are an effective and safe means of prevention for those at high risk regardless of lipid values.

Prognosis of acute coronary events is worse in patients living alone: the FINAMI myocardial infarction register.

BACKGROUND: Single living has been associated with a worse prognosis of acute coronary syndrome (ACS). We aimed to study the relation of sociodemographic characteristics to the morbidity, mortality, and case fatality (CF) of ACS in a large population-based ACS register. METHODS: The population-based FINAMI myocardial infarction register recorded 15,330 cases of ACS among persons aged 35-99 years in Finland in 1993-2002. Record linkage with the files of Statistics Finland provided information on sociodemographic characteristics (marital status, household size). RESULTS: ACS incidence and 28-day mortality rate were higher in unmarried men and women in all age groups. The prehospital CF of incident ACS was higher in single living and/or unmarried 35-64-year-old people. The 28-day CF was 26% (95% confidence interval, CI, 24-29%) in married men, 42% (95% CI 37-47%) in men who had previously been married, and 51% (95% CI 46-57%) in never-married men. Among women, the corresponding figures were 20% (95% CI 15-24%), 32% (95% CI 25-39%), and 43% (95% CI 31-56%). Most of these CF differences were apparent already at the prehospital phase. The only difference in treatment was that middle-aged men living alone or unmarried received thrombolysis less often. The disparities in ACS morbidity and mortality by marital status tended to widen during the study period. CONCLUSIONS: Single living and/or being unmarried increases the risk of having a heart attack and worsens its prognosis both in men and women regardless of age. Most of the excess mortality appears already before the hospital admission and seems not to be related to differences in treatment of ACS.

Effects of fenofibrate on cardiovascular events in patients with diabetes, with and without prior cardiovascular disease: The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

BACKGROUND: In the FIELD study, comparison of the effect of fenofibrate on cardiovascular disease (CVD) between those with prior CVD and without was a prespecified subgroup analysis. METHODS: The effects of fenofibrate on total CVD events and its components in patients who did (n = 2,131) and did not (n = 7,664) have a history of CVD were computed by Cox proportional hazards modeling and compared by testing for treatment-by-subgroup interaction. The analyses were adjusted for commencement of statins, use of other CVD medications, and baseline covariates. Effects on other CVD end points were explored. RESULTS: Patients with prior CVD were more likely than those without to be male, to be older (by 3.3 years), to have had a history of diabetes for 2 years longer at baseline, and to have diabetic complications, hypertension, and higher rates of use of insulin and CVD medications. Discontinuation of fenofibrate was similar between the subgroups, but more patients with prior CVD than without, and also more placebo than fenofibrate-assigned patients, commenced statin therapy. The borderline difference in the effects of fenofibrate between those who did (hazard ratio [HR] 1.02, 95% CI 0.86-1.20) and did not have prior CVD (HR 0.81, 95% CI 0.70-0.94; heterogeneity P = .045) became nonsignificant after adjustment for baseline covariates and other CVD medications (HR 0.96, 95% CI 0.81-1.14 vs HR 0.78, 95% CI 0.67-0.90) (heterogeneity P = .06). CONCLUSIONS: Our findings do not support treating patients with fenofibrate differently based on any history of CVD, in line with evidence from other trials.

Socioeconomic inequalities in the morbidity and mortality of acute coronary events in Finland: 1988 to 2002.

PURPOSE: To examine the changes in socioeconomic disparities in the incidence of coronary heart disease (CHD) and mortality in Finland and to analyze the effects of the severe economic recession of the early 1990s on these disparities. METHODS: The population-based FINAMI Myocardial Infarction (MI) register recorded all suspected MI events among men and women ages 35 to 99 years in four geographical areas of Finland. Record linkage with the files of Statistics Finland provided us with detailed information on the indicators of socioeconomic status (SES; income, education, and profession). Rates were expressed per 100,000 inhabitants of each socioeconomic group per year and age-standardized to the European standard population. Poisson regression was used for analyzing rate ratios and time trends of coronary events in different socioeconomic groups. RESULTS: The mortality rate ratio of coronary events among 35- to 64 year-old men was 5.21 (95% confidence interval, 4.23-6.41) when the lowest income sixth to the highest income sixth were compared. Among women, the respective rate ratio was 11.13 (5.77-21.45). Significant differences in the incidence and 28-day mortality by SES were seen also in the older age groups. Some socioeconomic differences were found in the proportions of patients receiving thrombolysis or undergoing early revascularization. No substantial changes were observed in inequalities between the socioeconomic groups during the study period. CONCLUSIONS: The excess CHD morbidity and mortality among persons with lower SES is still considerable in Finland, but the economic recession did not widen the differences.

Advancing the future of physical activity guidelines in Canada: an independent expert panel interpretation of the evidence.

The Canadian Society for Exercise Physiology, in partnership with the Public Health Agency of Canada, has initiated a review of their physical activity guidelines to promote healthy active living for Canadian children, youth, adults and older adults; previous guidelines were released in 2002, 2002, 1998 and 1999 respectively. Several background papers from this project were published recently and provide foundation evidence upon which to base new guidelines. Furthermore, comprehensive systematic reviews were completed to ensure a rigorous evaluation of evidence informing the revision of physical activity guidelines for asymptomatic populations. The overall guideline development process is being guided and assessed by the AGREE II instrument. A meeting of experts was convened to present the evidence complied to inform the guideline revisions. An independent expert panel was assembled to review the background materials and systematic reviews; listen to the presentations and discussions at the expert meeting; ask for clarification; and produce the present paper representing their interpretation of the evidence including grading of the evidence and their identification of needs for future research. The paper includes also their recommendations for evidence-informed physical activity guidelines.

Meta-analysis and imputation refines the association of 15q25 with smoking quantity.

Smoking is a leading global cause of disease and mortality. We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19)) that includes CHRNA5, CHRNA3 and CHRNB4, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref. 2) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of CHRNA5. Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3.

Adiponectin induced placental cell apoptosis could be mediated via the ADIPOR1-receptor in pre-eclampsia with IUGR.

AIMS: Adiponectin and leptin are members of the adipocytokine family. Adiponectin promotes and leptin inhibits apoptosis and both are regulators of angiogenesis. Adipocytokines and their receptors are expressed in the placenta, and in the pre-eclamptic (PE) mother the serum levels of both are higher than in healthy ones. Our aim was to study the expression of adiponectin, leptin, their receptor genes and apoptosis in severely PE and normal placentas. METHODS: The study group comprised 13 PE mothers and their 16 healthy controls. Placental biopsies were taken during cesarean section, the RNA was extracted and micro-array study was performed, followed by PCR and apoptosis studies. RESULTS: The placental expression level of the leptin and adiponectin receptor 1 genes was significantly higher in PE mothers than in controls. No significant changes were observed in the levels of the adiponectin, adiponectin receptor 2 and Leptin receptor genes. The expression of the Adiponectin gene was low. The rate of apoptosis was higher in the PE placentas. CONCLUSIONS: The activity of placental adipocytokines and their receptor genes in severe PE may suggest an important role in placental angiogenesis. Placental apoptosis induced by adiponectin could be mediated via the ADIPOR1-receptor.

Cholesterol absorption inhibitors in the treatment of hyperlipidemia: clinical outcomes in large clinical trials.

There is a large ongoing endpoint trial program using ezetimibe 10 mg combined with simvastatin 20, 40 or 80 mg in a number of patients with a high risk of major cardiovascular events. These studies include the measurement of carotid intima-media thickness in patients with familial hypercholesterolemia, aggressive lowering of LDL in patients with degenerative aortic stenosis, LDL lowering effects on cardiovascular risk and loss of renal function in patients with chronic kidney disease, and treatment of patients with acute coronary syndrome to very low LDL levels.

Reproductive history and carotid intima-media thickness.

BACKGROUND: Intima-media thickness (IMT) of the carotid arteries is a valid measure of preclinical atherosclerosis which may predict cardiovascular outcomes. Metabolic and hormonal changes associated with the reproductive history of women may contribute to the development of cardiovascular disease (CVD). METHODS: In a population-based cross-sectional study comprising 746 Finnish women, aged 45-74 years, associations of reproductive history (assessed by questionnaire) and measures of subclinical atherosclerosis (by ultrasonographic detection) were studied. Statistical methods included linear and logistic regression models. RESULTS: Mean carotid IMT was positively associated with parity, but after adjustment for age its statistical significance disappeared. Women with a history of stillbirth tended to have higher IMT than other women. History of hysterectomy was an independent determinant of carotid plaque in models with age, blood pressure, fasting blood glucose and cholesterol, body mass index (BMI), education and smoking (odds ratio (OR): 0.32; 95% confidence interval (CI): 0.11-0.96). But when oophorectomy (yes/no) was included in the model, this association lost its statistical significance (adjusted OR: 0.36; 95% CI: 0.11-1.22). A history of stillbirth was associated with an increased age-adjusted risk of plaque (OR=3.43; 95% CI: 1.07-11.05), but in the fully adjusted model it lost its statistical significance (OR=3.61; 95% CI: 0.86-15.23). CONCLUSION: Stillbirth was associated with increased risk of atherosclerotic plaque. Atherosclerosis is a lifelong process to which stillbirth is related. However, due to the cross-sectional design of this study, the causality of this association remains unclear.

Serum lipoprotein(a) level in relation to severity of coronary artery disease and coronary artery patency in acute myocardial infarction.

Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL)-like particle that may accelerate atherogenesis and promote thrombosis. In the present study, relationships between serum Lp(a) levels and the severity of coronary artery disease and infarct artery patency were studied in 14 patients with acute myocardial infarction. Lp(a) was measured by enzyme-linked immunosorbent assay and the timing of reperfusion was evaluated using the creatine kinase myosin-brain fraction and myoglobin release curves. Thrombolysis in Myocardial Infarction (TIMI) flow grade and severity of coronary artery disease were assessed using a scoring system based on coronary angiography performed during hospitalization and 6 months thereafter. The median Lp(a) level on admission was 127 (range 11-2,513) mg/l. The overall coronary score was higher in patients with Lp(a) levels greater than 127mg/l than in those with Lp(a) less than 127mg/l (P < 0.01). Lp(a) level correlated with the coronary score measured during hospitalization (r = 0.80, P < 0.01) and 6 months later (r = 0.79, P < 0.01). The timing of reperfusion and infarct artery patency were not depen dent on the serum Lp(a) level. The results show that the serum Lp(a) level is associated with the angiographic severity of coronary artery disease postmyocardial infarction bu does not determine the patency of the infarct-related artery.