Correlation of serum IGF-I and IGFBP-1 and -3 to cardiovascular risk indicators and early carotid atherosclerosis in healthy middle-aged men.

Objectives: IGF-I, IGFBP-1 and IGFBP-3 are putative mediators in cardiovascular disease. The present study examined (i) the correlations of circulating IGF-I, IGFBP-1 and IGFBP-3 to established cardiovascular risk factors and signs of early atherosclerosis as reflected by ultrasound measurement of common carotid intima-media thickness (IMT), and (ii) whether serum concentrations of these analytes are modulated during alimentary lipaemia.

Design: Cross-sectional clinical study.

Primary risk factors influence risk of recurrent myocardial infarction/death from coronary heart disease: results from the Stockholm Heart Epidemiology Program (SHEEP).

Background: Prognosis after a first myocardial infarction (MI) is influenced by primary risk factors as well as secondary risk factors. There is still a lack of follow-up studies of well-characterized patient cohorts assessing the relative importance of these factors.

Design: A cohort of 1635 patients (aged 45-70 years) surviving at least 28 days after a first MI were followed for 6-9 years with regard to recurrent MI/fatal coronary heart disease (CHD).

Markers of endothelial activity are related to components of the metabolic syndrome, but not to circulating concentrations of the advanced glycation end-product N epsilon-carboxymethyl-lysine in healthy Swedish men.

Endothelial function is considered important in the development of cardiovascular diseases and type 2 diabetes. Circulating advanced glycation end-products (AGEs) and dietary components have been shown to affect endothelial function in type 2 diabetics, but determinants of endothelial function in a non-diabetic population are more poorly investigated. Therefore, we investigated relationships between dietary habits, AGEs and endothelial activation in men with isolated metabolic disturbances.

The metabolic syndrome: prevalence and association to leisure-time and work-related physical activity in 60-year-old men and women.

Background And Aim: This study examined the prevalence of the metabolic syndrome and its association to lifestyle factors in 60-year-old men and women, with special emphasis on physical activity (PA).

Methods And Results: Every third 60-year-old man and woman in the Stockholm County, Sweden, was invited to a survey of cardiovascular risk factors. Seventy-seven percent of the sample, 4228 individuals, agreed to participate (2036 men and 2192 women).

Genetic and shared environmental factors do not confound the association between birth weight and hypertension: a study among Swedish twins.

Background: Studies have found associations between low birth weight and increased risks of cardiovascular diseases in adulthood. However, these associations could be due to confounding by genetic or socioeconomic factors.

Methods And Results: We performed a study on Swedish like-sexed twins with known zygosity who were born from 1926 to 1958.

Lifestyle intervention to prevent diabetes in men and women with impaired glucose tolerance is cost-effective.

Objectives: The Finnish Diabetes Prevention Study (DPS) was a randomized intervention program that evaluated the effect of intensive lifestyle modification on the development of diabetes mellitus type 2 in patients with impaired glucose tolerance. As such, a program is demanding in terms of resources; it is necessary to assess whether it would be money well spent. This determination was the purpose of this study.

Genetic influences on angina pectoris and its impact on coronary heart disease.

As functional properties of the coronaries may differ between coronary heart disease (CHD) patients with or without angina pectoris (AP), it is possible that different genetic mechanisms could be involved in the various CHD phenotypes. The primary aim of this study was, therefore, to determine the relative importance of genetic factors for AP as well as the impact of AP on CHD death in general. All same-sexed twins born between 1886 and 1958 included in the Swedish Twin Registry served as a base for this study.

Phenotype selection for detecting variable genes: a survey of cardiovascular quantitative traits and TNF locus polymorphism.

The practice of using discrete clinical diagnoses in genetic association studies has seldom led to a replicable genetic model. If, as the literature suggests, weak genotype-phenotype relationships are detected when clinical diagnoses are used, power might be increased by exploring more fundamental biological traits. Emerging solutions to this include directly modeling levels of the protein product of a gene (usually in plasma) and sequence variation specifically in/around that gene, as well as exploring multiple quantitative traits related to a disease of interest.

Retrospective analysis of coagulation factor II receptor (F2R) sequence variation and coronary heart disease in hypertensive patients.

Objectives: The purpose of this study was to evaluate the role of genetic variants within the coagulation factor II receptor (F2R) in the occurrence of coronary heart disease (CHD).

Methods And Results: Four SNPs (-1738 G/A, 2860 G/A, 2930 T/C, and 9113 C/A) and an ins/del polymorphism -506-/GGCCGCGGGAAGC (D/I), replicating a consensus sequence for Ets-1 transcription factor, and their related haplotypes were tested for association to CHD in 1600 hypertensive patients divided in 2 groups according to presence (cases, n=559) and absence (controls, n=1041) of CHD. Allele I at -506 locus was associated with increased risk of CHD under additive, dominant, and recessive models of inheritance (all P<0.

Blood pressure reduction and antihypertensive medication use in the losartan intervention for endpoint reduction in hypertension (LIFE) study in patients with hypertension and left ventricular hypertrophy.

Objective: To compare blood pressure response and antihypertensive medication use visit-by-visit from baseline in patients receiving losartan-based or atenolol-based therapy in the LIFE study.

Research Design: LIFE was a randomized, double-blind trial comparing losartan-based and atenolol-based treatment regimens on the primary composite endpoint of death, myocardial infarction (MI), or stroke in 9193 patients aged 55-80 years with hypertension and left ventricular hypertrophy. Systolic and diastolic, pulse, and mean arterial pressures, blood pressure responder rates, distribution of open-label antihypertensive agents utilized, and the proportion of patients on randomized treatment were determined for each group at each clinic visit over a follow-up period of at least 4 years.

Vascular disease in a population-based cohort of individuals hospitalised with coeliac disease.

Objectives: To evaluate the risk of cardiovascular disease in individuals with coeliac disease (CD).

Design: Swedish national hospital-based register data were used to identify 13,358 individuals who had been diagnosed with CD (1964-2003) and 64,118 age-matched and sex-matched individuals without CD. Cox regression was used to estimate the risk of vascular disease in subjects with CD.

Increased prevalence of diabetes among immigrants from non-European countries in 60-year-old men and women in Sweden.

Aims: To estimate the prevalence of risk factors for diabetes in subjects of foreign origin compared to Swedish-born.

Methods: A cross-sectional study with subjects included from a random sample of the population of in Stockholm County, Sweden, among 60-year-old men and women. Number in the analyzed groups were Swedish-born n=3329, immigrants from Europe n=654, and immigrants from non-European countries n=123.

The Swedish Twin Registry in the third millennium: an update.

The Swedish Twin Registry was first established in the late 1950s. Today it includes more than 170,000 twins--in principle, all twins born in Sweden since 1886. In this article we describe some ongoing and recently completed projects based on the registry.

The association between fibrinogen haplotypes and myocardial infarction in men is partly mediated through pleiotropic effects on the serum IL-6 concentration.

Background And Objectives: Fibrinogen haplotypes have been associated with risk of myocardial infarction (MI), independently of plasma fibrinogen concentration, and experimental data indicate that fibrinogen exerts pleiotropic effects on interleukin 6 (IL-6) production. Also, the coagulation factor XIII (gene symbol F13A1) Val34Leu haplotype tag single nucleotide polymorphism (htSNP) has been reported to exert pleiotropic effects on serum IL-6 concentration and to be associated with risk of MI. Therefore, in the present case-control study (a substudy to the Stockholm Heart Epidemiology Program), the effects of the fibrinogen gamma (FGG) 9340T>C [rs1049636], fibrinogen alpha (FGA) 2224G>A [rs2070011] and F13A1 Val34Leu [rs5985] htSNPs on concentrations of plasma fibrinogen and serum IL-6 and risk of MI were assessed.

Myocardial ischaemia in patients with peripheral arterial disease.

Aim: To study the relation between myocardial ischemia assessed with different techniques in patients with peripheral arterial disease (PAD) in comparison with a matched control group.

Methods: Ninety-nine male patients with PAD and 94 age- and sex-matched control subjects without PAD or ischaemic heart disease performed a exercise treadmill test, dipyridamole Tc-99m sestamibi myocardial perfusion SPECT (MPS) (43 controls) and 48-h ambulatory ECG (AECG)-monitoring (43 controls).

Results: Thirteen of 99 patients had irreversible and 24 of 99 had reversible perfusion defects in MPS in comparison with 0 of 43 and six of 43 of control subjects respectively (P<0.

The effect of leisure-time physical activity on the risk of acute myocardial infarction depending on body mass index: a population-based case-control study.

Background: High body mass index (BMI) and lack of physical activity have been recognized as important risk factors for coronary heart disease. The aim of the present study was to evaluate whether leisure-time physical activity compensates for the increased risk of acute myocardial infarction associated with overweight and obesity.

Methods: Data from the SHEEP (Stockholm Heart Epidemiology Program) study were used.

Decreased risk for myocardial infarction and lower tumor necrosis factor-alpha levels in carriers of variants of the PDCD1 gene.

Increasing interest has been directed toward the inflammatory mechanisms involved in the pathogenesis of myocardial infarction (MI). In the search for genetic mechanisms underlying these inflammatory components, we studied variants of programmed cell death-1 (PDCD1), an immunoinhibitory receptor that inhibits lymphocyte activation and cytokine production, previously shown to be associated with several autoimmune disorders. The PD1.

High intake of alcohol is associated with newly diagnosed diabetes in 60 years old men and women.

Background And Aims: Low or moderate alcohol intake has been found to be protective against the incidence of diabetes, while conflicting results have been found regarding high alcohol intake. This study aimed at evaluating the effect of alcohol intake on newly diagnosed diabetes among subjects aged 60 years in relation to anthropometric measurements, life-style and socio-economic factors.

Methods And Results: A population-based cross-sectional study of 4106 individuals, 1973 men and 2133 women, aged 60 years, in Stockholm County, Sweden.

Fatty acid handling protein expression in adipose tissue, fatty acid composition of adipose tissue and serum, and markers of insulin resistance.

Objective: Proteins involved in cellular fatty acid (FA) uptake and metabolism may be of relevance in the context of disturbed FA metabolism associated with insulin resistance. Therefore this study investigated relationships between FA handling protein mRNA expression in adipose tissue, FA composition of adipose tissue and serum, and markers of insulin resistance.

Subjects: 75 subjects with a range of insulin sensitivities recruited from a cohort of 294 healthy 63-year-old Swedish men.

Association between height and coronary heart disease mortality: a prospective study of 35,000 twin pairs.

An inverse association between height and risk of coronary heart disease (CHD) is well demonstrated, but it is not known whether this association is because of genetic factors, socioeconomic background, or other environmental factors. Four population-based twin cohorts with register-based follow-up data on CHD mortality from Denmark (1966-1996), Finland (1975-2001), and Sweden (1963-2001 and 1972-2001) were used to investigate this question; response rates varied between 65% and 86%. Together, the cohorts included 74,704 twin individuals (35,042 complete twin pairs) with 5,943 CHD deaths during 1.

Quantitative trait loci in ABCA1 modify cerebrospinal fluid amyloid-beta 1-42 and plasma apolipoprotein levels.

The ATP-binding cassette transporter A1 encoded by ABCA1 plays an integral role in the efflux of cellular cholesterol and phospholipids, but may also be a central mediator of beta-amyloid (Abeta) processing. Here, genetic association of the common R219K variant of ABCA1 is shown with cerebrospinal fluid (CSF) Abeta 1-42 levels, reinforcing emerging evidence of a connection between lipid and Abeta metabolism. In support of this finding we demonstrate for the first time that CSF cholesterol and Abeta 1-42 are correlated.

Antibodies of IgM subclass to phosphorylcholine and oxidized LDL are protective factors for atherosclerosis in patients with hypertension.

Objective: To determine the importance of antibodies against phosphorylcholine (PC) and oxidized low density lipoprotein (OxLDL) for development of atherosclerosis.

Methods And Results: Two hundred and twenty six individuals with established hypertension (diastolic pressure > 95mmHg) were from European Lacidipine Study on Atherosclerosis. Antibodies of IgG and IgM subclass were tested by ELISA against PC (aPC), cupper-oxidized (ox)- or malondialdehyde (MDA)-modified LDL.

Targeting the renin-angiotensin system for the reduction of cardiovascular outcomes in hypertension: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.

Agents that counteract the negative impact of the renin-angiotensin-aldosterone system (RAAS) are effective antihypertensives and reduce the risk of developing Type 2 diabetes. Contrary to common perception, angiotensin-converting enzyme inhibitors do not share the apparent benefit of angiotensin II receptor blockers (ARBs) in reducing risk of cardiovascular-disease outcomes, particularly stroke, in randomised clinical trials. RAAS agents, especially ARBs, are well tolerated.

Association of TNF-alpha serum levels and TNFA promoter polymorphisms with risk of myocardial infarction.

Elevated levels of tumor necrosis factor-alpha (TNF-alpha), and presence of polymorphisms of the TNFA gene have been implicated in cardiovascular disease pathogenesis. We explored the relationship between polymorphisms in the TNFA gene (-1031C/T, -863C/A -857T/C, -308G/A, -238G/A), protein levels of TNF-alpha and their association to myocardial infarction (MI) using a sample of 1213 post-MI patients and 1561 healthy controls. MI risk was higher among men with elevated TNF-alpha levels, with the highest compared to the lowest TNF-alpha quartile giving a 70% risk increase (OR [95% CI]: 1.

Measures of oxidized low-density lipoprotein and oxidative stress are not related and not elevated in otherwise healthy men with the metabolic syndrome.

Objective: The metabolic syndrome predisposes to the development of cardiovascular diseases. Oxidative stress and elevated circulating oxidized low-density lipoprotein (LDL) concentrations are related to cardiovascular disease and proposed to be features of the metabolic syndrome. F2-isoprostanes are lipid peroxidation products and considered the most reliable biomarkers of oxidative stress.