A genome-wide association study of IgM antibody against phosphorylcholine: shared genetics and phenotypic relationship to chronic lymphocytic leukemia.

Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWASs) in four European-ancestry cohorts, six single nucleotide polymorphisms (SNPs) in 11q24.

Role of Blood Lipids in the Development of Ischemic Stroke and its Subtypes: A Mendelian Randomization Study.

Background And Purpose: Statin therapy is associated with a lower risk of ischemic stroke supporting a causal role of low-density lipoprotein (LDL) cholesterol. However, more evidence is needed to answer the question whether LDL cholesterol plays a causal role in ischemic stroke subtypes. In addition, it is unknown whether high-density lipoprotein cholesterol and triglycerides have a causal relationship to ischemic stroke and its subtypes.

Irregularity and lack of p waves in short tachycardia episodes predict atrial fibrillation and ischemic stroke.

Background: Atrial fibrillation (AF) is defined as an irregular supraventricular tachycardia (SVT) without p waves, with duration >30 seconds. Whether AF characteristics during short SVT episodes predict AF and stroke is not known.

Objective: The purpose of this study was to determine whether irregularity and lack of p waves, alone or in combination, during short SVT episodes increase the risk of incident AF and ischemic stroke.

Markers of cardiovascular autonomic dysfunction predict COPD in middle-aged subjects.

Autonomic dysfunction is commonly observed in chronic obstructive pulmonary disease (COPD) and may relate to the known comorbidity with coronary artery disease (CAD). We hypothesised that clinical markers of cardiovascular autonomic dysfunction predict COPD in the population, independently of CAD.In a population-based cohort of 24 768 subjects (mean age 45 years) without baseline airflow obstruction, we analysed the cross-sectional relationship of one-minute orthostatic systolic blood pressure (SBP) and diastolic blood pressure (DBP) changes and resting heart rate with forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV).

Plasma Concentration of Caspase-8 Is Associated With Short Sleep Duration and the Risk of Incident Diabetes Mellitus.

Context: The biological mechanism for the association between sleep duration and incident diabetes mellitus (DM) is unclear. Sleep duration and caspase-8, a marker of apoptotic activity, have both been implicated in β-cell function.

Objective: To investigate the associations between sleep duration and plasma caspase-8 and incident DM, respectively.

A Genome-wide Study of Common and Rare Genetic Variants Associated with Circulating Thrombin Activatable Fibrinolysis Inhibitor.

Thrombin-activatable fibrinolysis inhibitor (TAFI) plays a central role in haemostasis, and plasma TAFI concentrations are heritable. Candidate gene studies have identified several variants within the gene encoding TAFI, , that explain part of the estimated heritability. Here, we describe an exploratory genome-wide association study to identify novel variants within and outside of the locus that influence plasma concentrations of intact TAFI and/or the extent of TAFI activation (measured by released TAFI activation peptide, TAFI-AP) amongst 3,260 subjects from Southern Sweden.

B-type natriuretic peptide for prediction of incident clinically significant abdominal aortic aneurysm: A population-based prospective study.

Pathogenesis of abdominal aortic aneurysm (AAA) is unclear. The aim of this study was to evaluate inflammatory and hemodynamic plasma biomarkers as predictors for AAA in the prospective longitudinal cohort of middle-aged individuals from the cardiovascular cohort of the Malmö Diet and Cancer Study ( n=5551; 1991-94). C-reactive protein, cystatin C, copeptin, N-terminal pro-B-type natriuretic peptide (N-BNP), midregional pro-atrial natriuretic peptide (MR-proANP) and conventional risk factors at baseline were measured in patients with incident AAA during follow-up and compared to individuals without a diagnosis of AAA.

Factor V Leiden paradox in a middle-aged Swedish population: A prospective study.

Few prospective studies have examined the factor V paradox: factor V Leiden (FVL) is a stronger risk factor for deep venous thrombosis (DVT) than for pulmonary embolism (PE). The present study, to the best of our knowledge, is the first population-based study aimed to examine the relationship between FVL and incidence of venous thromboembolism (VTE), DVT and PE in a prospective cohort study of middle-aged Swedish individuals. FVL was determined in 4890 subjects (aged 46-68 years, 57% women) from the general population without previous VTE or cancer, who participated in the Malmö Diet and Cancer study between 1991 and 1994.

Elevated Markers of Death Receptor-Activated Apoptosis are Associated with Increased Risk for Development of Diabetes and Cardiovascular Disease.

Background: An increased rate of cell death by apoptosis has been implicated in both diabetes and atherosclerosis. Apoptosis can be induced through activation of the death receptors TNF receptor 1 (TNFR-1), TRAIL receptor 2 (TRAILR-2) and Fas. Soluble forms of these receptors are found in plasma.

Cadmium, Carotid Atherosclerosis, and Incidence of Ischemic Stroke.

Background: Exposure to cadmium has been associated with carotid plaques, inflammation in carotid plaques, and increased risk of ischemic stroke. This study examined the separate and interacting effects of blood cadmium levels and carotid plaques on the risk of incident ischemic stroke.

Methods And Results: Cadmium levels were measured in 4156 subjects (39.

Postmenopausal hormone therapy and risk of stroke: A pooled analysis of data from population-based cohort studies.

Background: Recent research indicates a favourable influence of postmenopausal hormone therapy (HT) if initiated early, but not late, on subclinical atherosclerosis. However, the clinical relevance of timing of HT initiation for hard end points such as stroke remains to be determined. Further, no previous research has considered the timing of initiation of HT in relation to haemorrhagic stroke risk.

Incident diabetes mellitus may explain the association between sleep duration and incident coronary heart disease.

Aims/hypothesis: Sleep duration is a risk factor for incident diabetes mellitus and CHD. The primary aim of the present study was to investigate, in sex-specific analyses, the role of incident diabetes as the possible biological mechanism for the reported association between short/long sleep duration and incident CHD. Considering that diabetes is a major risk factor for CHD, we hypothesised that any association with sleep duration would not hold for cases of incident CHD occurring before incident diabetes ('non-diabetes CHD') but would hold true for cases of incident CHD following incident diabetes ('diabetes-CHD').

Genetic determinants of growth hormone and GH-related phenotypes.

Background: Higher fasting Growth Hormone (GH) has been associated with increased cardiovascular morbidity and mortality. Our objective was to find genetic determinants of fasting GH in order to facilitate future efforts of analyzing the association between fasting growth hormone and cardiovascular disease. A genome-wide association study (GWAS) was performed in a discovery cohort of 4134 persons (58% females; age 46-68 yrs), linking SNPs to fasting hs-GH.

Complement C3 Associates With Incidence of Diabetes, but No Evidence of a Causal Relationship.

Purpose: This study explored whether complement factor 3 (C3) in plasma is associated with incidence of diabetes in a population-based cohort. We also identified genetic variants related to C3 and explored whether C3 and diabetes share common genetic determinants.

Methods: C3 was analyzed in plasma from 4368 nondiabetic subjects, 46 to 68 years old, from the Malmö Diet and Cancer Study.

Separate and combined associations of obesity and metabolic health with coronary heart disease: a pan-European case-cohort analysis.

Aims: The hypothesis of 'metabolically healthy obesity' implies that, in the absence of metabolic dysfunction, individuals with excess adiposity are not at greater cardiovascular risk. We tested this hypothesis in a large pan-European prospective study.

Methods And Results: We conducted a case-cohort analysis in the 520 000-person European Prospective Investigation into Cancer and Nutrition study ('EPIC-CVD').

Partial Mediation by Cadmium Exposure of the Association Between Tobacco Smoking and Atherosclerotic Plaques in the Carotid Artery.

Exposure to cadmium confers increased cardiovascular risk. Tobacco smoke contains cadmium, which, hypothetically, may mediate parts of the tobacco-associated risk of developing atherosclerotic plaques. Baseline data from the Swedish Malmö Diet and Cancer cohort (1991-1996) were used to test this hypothesis.

Smokeless tobacco (snus) use and colorectal cancer incidence and survival: Results from nine pooled cohorts.

Aims: Although smoking is considered to be an established risk factor for colorectal cancer, the current evidence on the association between smokeless tobacco and colorectal cancer is scant and inconclusive. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess this association.

Methods: A total of 417,872 male participants from nine cohort studies across Sweden were followed up for incidence of colorectal cancer and death.

Outcome of intra-arterial thrombolysis in patients with diabetes and acute lower limb ischemia: a propensity score adjusted analysis.

The presence of diabetes mellitus is rarely addressed in acute lower limb ischaemia (ALLI). The aim of this study was to evaluate the outcome of local intra-arterial thrombolysis for ALLI in patients with diabetes mellitus (DM). Outcome of all thrombolytic events performed in an endovascular first-strategy centre during a 13-year period between 2001 and 2013 in patients with ALLI were followed to January 2017.

Arterial Stiffness and Incidence of Diabetes: A Population-Based Cohort Study.

Objective: Diabetes is known to be associated with increased arterial stiffness. However, the temporal association between increased carotid-femoral pulse wave velocity (c-f PWV) and diabetes is unclear. The aim of this study is to explore the relationship between arterial stiffness, as determined by c-f PWV, and incidence of diabetes.

Eosinophil Cationic Protein, Carotid Plaque, and Incidence of Stroke.

Background And Purpose: ECP (eosinophil cationic protein) is a marker of eosinophil activity and degranulation, which has been linked to atherosclerosis and cardiovascular disease. We examined the relationship between ECP, carotid plaque, and incidence of stroke in a prospective population-based cohort.

Methods: The subjects participated in the Malmö Diet and Cancer Study between 1991 and 1994.

Genetic Interactions with Age, Sex, Body Mass Index, and Hypertension in Relation to Atrial Fibrillation: The AFGen Consortium.

It is unclear whether genetic markers interact with risk factors to influence atrial fibrillation (AF) risk. We performed genome-wide interaction analyses between genetic variants and age, sex, hypertension, and body mass index in the AFGen Consortium. Study-specific results were combined using meta-analysis (88,383 individuals of European descent, including 7,292 with AF).

Tumor Necrosis Factor Receptor 1 and 2 Are Associated With Risk of Intracerebral Hemorrhage.

Background And Purpose: Raised plasma concentrations of tumor necrosis factor receptors (TNFR) have been linked to arterial stiffness, cerebral microbleeds, and vascular events. The aim of this study was to investigate the association of circulating levels of TNFR1 and TNFR2 with risk for future intracerebral hemorrhage (ICH).

Methods: The population-based MDCS cohort (Malmö Diet and Cancer Study; n=28 449) was conducted in 1991 to 1996.

Circulating Midregional Proadrenomedullin and Risk of Incident Abdominal Aortic Aneurysm: A Prospective Longitudinal Cohort Study.

Prospective clinical plasma biomarker studies in abdominal aortic aneurysm (AAA) pathogenesis have been hampered by the need for very large cohorts and long follow-up time. The main aim of the present study was to evaluate the association of adrenomedullin, a cardiovascular (CV) stress marker, and incident AAA risk. Prospective longitudinal cohort of middle-aged individuals from the CV cohort of the Malmö Diet and Cancer Study (n = 5551; 1991-1994) was assessed.

Acute phase proteins as prospective risk markers for arterial stiffness: The Malmö Diet and Cancer cohort.

Background And Objectives: Arterial stiffness plays a significant role in the development and progression of adverse cardiovascular events and all-cause mortality. This observational study aims to explore the relationship between six acute phase proteins namely, ceruloplasmin, alpha-1-antitrypsin, orosomucoid, haptoglobin, complement C3 and C-reactive protein (CRP), and carotid-femoral pulse wave velocity (c-f PWV) in a population-based cohort, and to also explore the effect of low-grade inflammation on the relationship between diabetes and c-f PWV.

Method: The study consisted of participants from the Malmö Diet and Cancer study with data from baseline examinations (1991-1994) and follow-up examinations (2007-2012).