Bo Hedblad

Publications (248) View all

• Article: Smoking and obesity associated BDNF gene variance predicts total and cardiovascular mortality in smokers.

  Sara Halldén, Marketa Sjögren, Bo Hedblad, Gunnar Engström, Krzysztof Narkiewicz, Michal Hoffmann, Björn Wahlstrand, Thomas Hedner, Olle Melander
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  ABSTRACT: OBJECTIVE: The brain derived neurotrophic factor (BDNF) locus has been implicated in psychiatric and substance related disorders. Recent genome-wide association studies (GWAS) have shown strong associations between single nucleotide polymorphisms in BDNF, smoking behaviour and high body mass index (BMI). Our aim was to test whether genetic BDNF variation alters the risk of smoking related morbidity and mortality. DESIGN: Cox proportional hazards models were used to relate the BDNF rs4923461(A/G) polymorphisms to all-cause, cancer and cardiovascular mortality and cardiovascular disease (CVD) incidence adjusted for age, sex, BMI, and smoking quantity. SETTING: The Malmö Diet and Cancer Study (MDCS), a population based prospective cohort study (n=30 447). PATIENTS: We obtained complete data on 25 071 subjects, of whom 6507 were current smokers and 18 564 were non-smokers who underwent a baseline examination from 1991-1996. MAIN OUTCOME MEASURES: During a mean follow-up time of 12 years, 1049 deaths (346 cardiovascular deaths and 492 cancer deaths) and 802 incident CVD events occurred among current smokers. RESULTS: The major allele (A) of rs4923461 was significantly associated with ever having smoked (p=0.03) and high BMI (p=0.001). The A-allele was associated with risk of all-cause (HR=1.12, 95% CI 1.00 to 1.25; p<0.05) and CVD (HR=1.23, 95% CI 1.01 to 1.49; p=0.04) mortality. There was no significant association between the rs4923461 and cancer mortality or CVD incidence. CONCLUSIONS: Our data suggest that smoking- and obesity-associated variation of the BDNF gene affects the risk of death, especially due to cardiovascular causes, in smokers. Determination of the BDNF genotype in smokers may guide the need for smoking cessation interventions.
  Heart (British Cardiac Society) 04/2013; · 4.22 Impact Factor
• Article: Chromosome 9p21 genetic variation explains 13% of cardiovascular disease incidence but does not improve risk prediction.

  Klas Gränsbo, Peter Almgren, Marketa Sjögren, J Gustav Smith, Gunnar Engström, Bo Hedblad, Olle Melander
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  ABSTRACT: OBJECTIVES: To evaluate the proportion of cardiovascular disease (CVD) incidence that is explained by genetic variation at chromosome 9p21 and to test whether such variation adds incremental information with regard to CVD prediction, beyond traditional risk factors. DESIGN, SETTING AND PARTICIPANTS: rs4977574 on chromosome 9p21 was genotyped in 24,777 subjects from the Malmö Diet and Cancer study who were free from CVD prior to the baseline examination. Association between genotype and incident CVD (n=2668) during a median follow-up of 11.7 years was evaluated in multivariate Cox proportional hazard models. Analyses were performed in quartiles of baseline age, and linear trends in effect size across age groups were estimated in logistic regression models. RESULTS: In additive models, chromosome 9p21 significantly predicted CVD in the entire population (hazard ratio 1.17 per G allele, 95% confidence interval 1.11-1.23, P<0.001). Effect estimates increased from the highest (Q4) to the lowest quartile (Q1) of baseline age, but this trend was not significant. The overall population attributable risk conferred by chromosome 9p21 in fully adjusted models was 13%, ranging from 17% in Q1 to 11% in Q4. Addition of chromosome 9p21 to traditional risk factors only marginally improved predictive accuracy. CONCLUSION: The high population attributable risk conferred by chromosome 9p21 suggests that future interventions interfering with downstream mechanisms of the genetic variation may affect CVD incidence over a broad range of ages. However, variation of chromosome 9p21 alone does not add clinically meaningful information in terms of CVD prediction beyond traditional risk factors at any age. © 2013 The Association for the Publication of the Journal of Internal Medicine.
  Journal of Internal Medicine 03/2013; · 5.48 Impact Factor
• Article: Mild Renal Dysfunction and Metabolites Tied to Low HDL Cholesterol are Associated with Monocytosis and Atherosclerosis.

  Anjali Ganda, Martin Magnusson, Laurent Yvan-Charvet, Bo Hedblad, Gunnar Engström, Ding Ai, Thomas J Wang, Robert E Gerszten, Olle Melander, Alan R Tall
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  ABSTRACT: BACKGROUND: The number of circulating blood monocytes impacts atherosclerotic lesion size and in mouse models, elevated levels of high density lipoprotein-cholesterol (HDL-C) suppress blood monocyte counts and atherosclerosis. We hypothesized that individuals with mild renal dysfunction at increased cardiovascular risk would have reduced HDL levels, high blood monocyte counts, and accelerated atherosclerosis. METHODS AND RESULTS: To test whether mild renal dysfunction is associated with increase in a leukocyte subpopulation rich in monocytes that has a known association with future coronary events, we divided individuals from the Malmö Diet and Cancer study (MDC) into baseline cystatin C quintiles (N=4757). Lower levels of renal function were accompanied by higher monocyte counts, and monocytes were independently associated with carotid bulb intima-media thickness cross-sectionally (p= 0.02). Cystatin C levels were positively and plasma HDL-C levels negatively associated with monocyte counts at baseline, following adjustment for traditional risk factors. Several amino acid metabolites tied to low HDL-C and insulin resistance measured in a subset of individuals (N= 752) using liquid chromatography-mass spectrometry were independently associated with a 22-34% increased risk of being in the top quartile of monocytes (p<0.05). CONCLUSIONS: A low HDL-C, insulin resistance phenotype occurs in subjects with mild renal dysfunction and is associated with elevated monocytes and atherosclerosis. High blood monocytes may represent a previously unrecognized mechanism underlying the strong relationship between cystatin C and cardiovascular risk.
  Circulation 02/2013; · 14.74 Impact Factor
• Article: Association between CD8(+) T cell subsets and cardiovascular disease.

  Daniel Kolbus, Irena Ljungcrantz, Linda Andersson, Bo Hedblad, Gunilla Nordin Fredrikson, Harry Björkbacka, Jan Nilsson
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  ABSTRACT: OBJECTIVES: The findings of experimental studies suggest that the immune system plays a key role in atherosclerosis but the clinical importance of different immune cells in cardiovascular disease remains poorly characterized. In this study we investigated the association between CD8(+) T cells and carotid disease as well as development of cardiovascular disease events. DESIGN: The study cohort comprised 700 subjects from the cardiovascular arm of the Malmö Diet and Cancer Study. Peripheral blood mononuclear cells, obtained at the 1991-1994 baseline investigation and stored at -140°C, were thawed and the different CD8(+) T cell populations analysed by flow cytometry. Baseline carotid intima-media thickness and stenosis were assessed by ultrasonography and clinical events were monitored through validated national registers. RESULTS: Subjects with a high fraction of CD8(+) T cells were characterized by decreased cytokine release from activated leukocytes, metabolic signs of insulin resistance and increased incidence of coronary events; hazard ratios (95% confidence intervals) for the second and third tertiles of CD8(+) T cells were 2.57 (1.16, 5.67) and 2.61 (1.19, 5,71), respectively, in a Cox proportional hazards regression model. Correlations were found between the fraction of CD8(+) CD25(+) T cells and the degree of carotid stenosis (r=0.11, P<0.01), and between the CD8(+) CD56(-) IFN-γ(+) T cell fraction and the degree of stenosis (r=-0.18, P<0.005). The association between CD8(+) CD56(-) IFN-γ(+) T cells and carotid stenosis remained significant after controlling for major cardiovascular disease risk factors. CONCLUSION: The present study provides prospective clinical evidence for a role of CD8(+) T cells in cardiovascular disease and suggests the existence of CD8(+) T cell subsets with different pathological functions. © 2013 The Association for the Publication of the Journal of Internal Medicine.
  Journal of Internal Medicine 01/2013; · 5.48 Impact Factor
• Article: T-Helper 2 Immunity Is Associated With Reduced Risk of Myocardial Infarction and Stroke.

  Daniel Engelbertsen, Linda Andersson, Irena Ljungcrantz, Maria Wigren, Bo Hedblad, Jan Nilsson, Harry Björkbacka
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  ABSTRACT: OBJECTIVE: Experimental studies in mice have attributed T-helper (Th) 1 and Th2 cells important roles in atherosclerosis, but the clinical importance of these cells in cardiovascular disease (CVD) remains to be clarified. Here, we investigated associations between Th1 and Th2 cells, carotid intima-media thickness, and cardiovascular risk. METHODS AND RESULTS: Blood drawn at baseline and incident cardiovascular events during 15-year follow-up were assessed in 700 participants. Baseline Th1 (CD3(+)CD4(+)interferon-γ(+)) and Th2 (CD3(+)CD4(+)IL-4(+)) cells were analyzed by flow cytometry, and cytokine-release from activated mononuclear leukocytes was measured by multiplex technology. High numbers of Th2 cells were independently associated with decreased mean common carotid intima-media thickness. High numbers of Th2 cells were also independently associated with a reduced risk of acute myocardial infarction in women (hazard ratio, 0.19; 95% confidence interval, 0.06-0.56; P=0.002 for the highest versus the lowest tertile of Th2 cells). Moreover, release of the Th2 cytokine IL-4 from activated mononuclear leukocytes was independently associated with a reduced risk of CVD. No independent associations between Th1 cells and carotid intima-media thickness or CVD risk were found. CONCLUSIONS: Our observations provide the first clinical evidence for a protective role of Th2 immunity in CVD. They also suggest this protection is more prominent in women than in men. In spite of convincing evidence from experimental studies, we found no support for a role of Th1 immunity in CVD.
  Arteriosclerosis Thrombosis and Vascular Biology 01/2013; · 6.37 Impact Factor