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Asvold, B. O., Bjoro, T., Platou, C., & Vatten, L. J. (2012). Thyroid function and the risk of coronary heart disease: 12-year follow-up of the HUNT study in Norway. Clin Endocrinol (Oxf), 77(6), 911–917.
Abstract: OBJECTIVE: In a mortality follow-up of the HUNT Study, serum TSH within the reference range was positively associated with the risk of coronary death in women. We now aimed to confirm the association of high serum TSH with the risk of coronary heart disease, using hospital-based diagnoses of myocardial infarction. DESIGN: Prospective population-based study with linkage to hospital information on myocardial infarction and to the national Cause of Death Registry. PARTICIPANTS: A total of 26, 707 people without previously known thyroid or cardiovascular disease or diabetes at baseline. MEASUREMENTS: Hazard ratios (HR) of coronary death and HRs of hospitalization with a first-time acute myocardial infarction, by baseline thyroid function. RESULTS: During 12, years of follow-up, 960 (3.6%) participants had been hospitalized with first-time myocardial infarction and 558 (2.1%) had died from coronary heart disease. High TSH within the reference range was associated with increased risk of coronary death in women (P(trend) 0.005), but not in men. The risk of coronary death was also increased among women with subclinical hypothyroidism or subclinical hyperthyroidism, compared to women with TSH of 0.50-1.4 mU/l. However, thyroid function was not associated with the risk of being hospitalized with myocardial infarction. CONCLUSIONS: High serum TSH was associated with increased mortality from coronary heart disease in women, but we found no association of thyroid function with the risk of being hospitalized with myocardial infarction. Thus, the morbidity finding does not confirm the suggestion that low thyroid function within the clinically normal range is associated with increased risk of coronary heart disease.
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Ganz, P., Heidecker, B., Hveem, K., Jonasson, C., Kato, S., Segal, M. R., et al. (2016). Development and Validation of a Protein-Based Risk Score for Cardiovascular Outcomes Among Patients With Stable Coronary Heart Disease. Jama, 315(23), 2532–2541.
Abstract: IMPORTANCE: Precise stratification of cardiovascular risk in patients with coronary heart disease (CHD) is needed to inform treatment decisions. OBJECTIVE: To derive and validate a score to predict risk of cardiovascular outcomes among patients with CHD, using large-scale analysis of circulating proteins. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of participants with stable CHD. For the derivation cohort (Heart and Soul study), outpatients from San Francisco were enrolled from 2000 through 2002 and followed up through November 2011 (
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Gustad, L. T., Laugsand, L. E., Janszky, I., Dalen, H., & Bjerkeset, O. (2014). Symptoms of anxiety and depression and risk of heart failure: the HUNT Study. Eur J Heart Fail, .
Abstract: AIMS: Symptoms of anxiety and depression often co-exist with cardiovascular disease, yet little is known about the prospective risk for heart failure (HF) in people with symptoms of depression and anxiety. We aimed to study these prospective associations using self-reported symptoms of anxiety, depression, and mixed symptoms of anxiety and depression (MSAD) in a large population sample. METHODS AND RESULTS: In the second wave of the Nord-Trondelag Health Study (HUNT 2, 1995-1997), Norway, baseline data on symptoms of anxiety and depression, socio-demographic variables, health status including cardiovascular risk factors, and common chronic somatic diseases were registered for 62 567 adults, men and women, free of known HF. The cohort was followed for incident HF from baseline throughout 2008. A total of 1499 cases of HF occurred during a mean follow-up of 11.3 years (SD = 2.9), identified either in hospital registers or by the National Cause of Death Registry. There was no excess risk for future HF associated with symptoms of anxiety or MSAD at baseline. For depression, the multi-adjusted hazard ratios for HF were 1.07 (0.87-1.30) for moderate symptoms and 1.41 (1.07-1.87) for severe symptoms (P for trend 0.026). Established cardiovascular risk factors, acute myocardial infarction (AMI) prior to baseline, and adjustment for incident AMI as a time-dependent covariate during follow-up had little influence on the estimates. CONCLUSION: Symptoms of depression, but not symptoms of anxiety or MSAD, were associated with increased risk for HF in a dose-response manner. The increased risk could not be fully explained by cardiovascular or socio-economic risk factors, or by co-morbid AMI.
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Laugsand, L. E., Strand, L. B., Platou, C., Vatten, L. J., & Janszky, I. (2014). Insomnia and the risk of incident heart failure: a population study. Eur Heart J, 35(21), 1382–1393.
Abstract: AIMS: Insomnia is highly prevalent among heart failure patients, but only a few small studies have investigated insomnia symptoms and risk of heart failure. We aimed to assess the prospective association between self-reported insomnia symptoms and the risk of incident heart failure in a large Norwegian cohort. METHODS AND RESULTS: Baseline data on insomnia symptoms, including difficulty initiating sleep, difficulty maintaining sleep and having non-restorative sleep, socio-demographic variables, and health status, including established cardiovascular risk factors, were collected from 54 279 men and women 20-89 years of age who participated in the Nord-Trondelag Health study (HUNT) between 1995 and 1997 and were free from known heart failure at baseline. The cohort was followed for incident heart failure from baseline through 2008. We used Cox proportional hazard models to assess the association of baseline insomnia symptoms with the risk of heart failure. A total of 1412 cases of heart failure occurred during a mean follow-up of 11.3 years (SD = 2.9 years), either identified at hospitals or by the National Cause of Death Registry. There was a dose-dependent association between the number of insomnia symptoms and risk of heart failure. The multi-adjusted hazard ratios were 0.96 (0.57-1.61), 1.35 (0.72-2.50), and 4.53 (1.99-10.31) for people with one, two, and three insomnia symptoms, compared with people with none of the symptoms (P for trend 0.021). CONCLUSIONS: Insomnia is associated with an increased risk of incident heart failure. If our results are confirmed by others and causation is proved, evaluation of insomnia symptoms might have consequences for cardiovascular prevention.
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Morkedal, B., Vatten, L. J., Romundstad, P. R., Laugsand, L. E., & Janszky, I. (2014). Risk of myocardial infarction and heart failure among metabolically healthy but obese individuals: HUNT (Nord-Trondelag Health Study), Norway. Journal of the American College of Cardiology, 63(11), 1071–1078.
Abstract: OBJECTIVES: This study sought to investigate whether obesity in the absence of metabolic abnormalities might be a relatively benign condition in relation to acute myocardial infarction (AMI) and heart failure (HF). BACKGROUND: The results of previous studies are conflicting for AMI and largely unknown for HF, and the role of the duration of obesity has not been investigated. METHODS: In a population-based prospective cohort study, a total of 61,299 men and women free of cardiovascular disease were classified according to body mass index (BMI) and metabolic status at baseline. BMI also was measured 10 and 30 years before baseline for 27,196 participants. RESULTS: During 12 years of follow-up, 2,547 participants had a first AMI, and 1,201 participants had a first HF. Compared with being normal weight (BMI <25 kg/m(2)) and metabolically healthy, the multivariable-adjusted hazard ratio (HR) for AMI was 1.1 (95% confidence interval [CI]: 0.9 to 1.4) among obese (BMI >/=30 kg/m(2)) and metabolically healthy participants and 2.0 (95% CI: 1.7 to 2.3) among obese and metabolically unhealthy participants. We found similar results for severe (BMI >/=35 kg/m(2)), long-lasting (>30 years), and abdominal obesity stratified for metabolic status. For HF, the HRs associated with obesity were 1.7 (95% CI: 1.3 to 2.3) and 1.7 (95% CI: 1.4 to 2.2) for metabolically healthy and unhealthy participants, respectively. Severe and long-lasting obesity were particularly harmful in relation to HF, regardless of metabolic status. CONCLUSIONS: In relation to AMI, obesity without metabolic abnormalities did not confer substantial excess risk, not even for severe or long-lasting obesity. For HF, even metabolically healthy obesity was associated with increased risk, particularly for long-lasting or severe obesity.
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Selmeryd, J., Henriksen, E., Dalen, H., & Hedberg, P. (2017). Derivation and Evaluation of Age-Specific Multivariate Reference Regions to Aid in Identification of Abnormal Filling Patterns: The HUNT and VaMIS Studies. JACC Cardiovasc Imaging, .
Abstract: OBJECTIVES: This study aimed to derive age-specific multivariate reference regions (MVRs) able to classify subjects into those having normal or abnormal filling patterns and to evaluate the prognostic impact of this classification. BACKGROUND: The integration of several parameters is necessary to diagnose disorders of left ventricular (LV) filling because no single measurement accurately describes the complexity of diastolic function. However, no generally accepted validated multiparametric algorithm currently exists. METHODS: A cohort of 1,240 apparently healthy subjects from HUNT (the Nord-Trondelag Health Study) with measured early (E) and late (A) mitral inflow velocity and early mitral annular diastolic tissue velocity (e') were used to derive univariate 95% reference bands and age-specific MVRs. Subsequently, the prognostic impact of this MVR-based classification was evaluated by Cox regression in a community-based cohort (n = 726) and in a cohort of subjects with recent acute myocardial infarction (n = 551). Both evaluation cohorts were derived from VaMIS (the Vastmanland Myocardial Infarction Study). RESULTS: Univariate reference bands and MVRs are presented graphically and as regression equations. After adjustment for sex, age, hypertension, body mass index, diabetes, prior ischemic heart disease, LV mass, LV ejection fraction, and left atrial size, the hazard ratio associated with abnormal filling patterns in the community-based cohort was 3.5 (95% confidence interval: 1.7 to 7.0; p < 0.001) and that in the acute myocardial infarction cohort was 1.8 (95% confidence interval: 1.1 to 2.8; p = 0.011). CONCLUSIONS: This study derived age-specific MVRs for identification of abnormal LV filling patterns and showed, in a community-based cohort and in a cohort of patients with recent acute myocardial infarction, that these MVRs conveyed important prognostic information. An MVR-based classification of LV filling patterns could lead to more consistent diagnostic algorithms for identification of different filling disorders.
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Selmeryd, J., Henriksen, E., Dalen, H., & Hedberg, P. (2018). Derivation and Evaluation of Age-Specific Multivariate Reference Regions to Aid in Identification of Abnormal Filling Patterns: The HUNT and VaMIS Studies. JACC Cardiovasc Imaging, 11(3), 400–408.
Abstract: OBJECTIVES: This study aimed to derive age-specific multivariate reference regions (MVRs) able to classify subjects into those having normal or abnormal filling patterns and to evaluate the prognostic impact of this classification. BACKGROUND: The integration of several parameters is necessary to diagnose disorders of left ventricular (LV) filling because no single measurement accurately describes the complexity of diastolic function. However, no generally accepted validated multiparametric algorithm currently exists. METHODS: A cohort of 1,240 apparently healthy subjects from HUNT (Nord-Trondelag Health Study) with measured early (E) and late (A) mitral inflow velocity and early mitral annular diastolic tissue velocity (e') were used to derive univariate 95% reference bands and age-specific MVRs. Subsequently, the prognostic impact of this MVR-based classification was evaluated by Cox regression in a community-based cohort (n = 726) and in a cohort of subjects with recent acute myocardial infarction (n = 551). Both evaluation cohorts were derived from VaMIS (the Vastmanland Myocardial Infarction Study). RESULTS: Univariate reference bands and MVRs are presented graphically and as regression equations. After adjustment for sex, age, hypertension, body mass index, diabetes, prior ischemic heart disease, LV mass, LV ejection fraction, and left atrial size, the hazard ratio associated with abnormal filling patterns in the community-based cohort was 3.5 (95% confidence interval: 1.7 to 7.0; p < 0.001) and that in the acute myocardial infarction cohort was 1.8 (95% confidence interval: 1.1 to 2.8; p = 0.011). CONCLUSIONS: This study derived age-specific MVRs for identification of abnormal LV filling patterns and showed, in a community-based cohort and in a cohort of patients with recent acute myocardial infarction, that these MVRs conveyed important prognostic information. An MVR-based classification of LV filling patterns could lead to more consistent diagnostic algorithms for identification of different filling disorders.
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