Jørgen Jeppesen

Glostrup Hospital, Glostrup, Capital Region, Denmark

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Publications (99)519.44 Total impact

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    ABSTRACT: Obesity is a strong risk factor for hypertension but the mechanism linking obesity to hypertension is not fully elucidated. In obesity, circulating concentrations of adiponectin are decreased and hypoadiponectinaemia has in some but not all studies been associated with increased risk of hypertension. Due to this inconsistency, we decided to study adiponectin from two aspects in a cross-sectional in vivo study and in an experimental in vitro study. In the cross-sectional study, 103 men with body mass index (BMI) ≥30.0 kg/m(2) were studied; 63 had 24-hr ambulatory blood pressure (ABP) ≥130/80 mmHg (ObeseHT) and 40 had 24-hr ABP <130/80 mmHg (ObeseNT). As controls, we studied 27 men with BMI between 20.0 and 24.9 kg/m(2) and 24-hr ABP <130/80 mmHg (LeanNT). Serum concentrations of adiponectin and body composition using dual energy X-ray absorptiometry scanning were determined. In vitro, the direct vasomotor response of adiponectin was tested on subcutaneous resistance arteries from human abdominal adipose tissue. The 2 obese groups had lower adiponectin concentrations compared with LeanNT (P<0.01) (median (interquartile range)): ObeseHT 6.5 (5.1-8.3) mg/L; ObeseNT 6.6 (5.2-7.8) mg/L; and LeanNT 9.4 (6.7-12.4) mg/L, with no significant difference in adiponectin concentrations (or body composition) between ObeseHT and ObeseNT (P=0.67). In vitro, recombinant human adiponectin neither had any direct vasodilatory effect nor did adiponectin affect angiotensin II-stimulated vasoconstriction. In conclusion, obese, hypertensive men have similar serum concentrations of adiponectin as obese, normotensive men. In combination with the in vitro data, these findings question a pathogenic role of adiponectin in human hypertension. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Basic & Clinical Pharmacology & Toxicology 08/2015; DOI:10.1111/bcpt.12452 · 2.38 Impact Factor
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    DESCRIPTION: The Prevalence and Incidence of Glaucoma in Denmark in a Fifteen Year Period: A Nationwide Study
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    ABSTRACT: Background: Being overweight or obese is associated with a greater risk of coronary heart disease and stroke compared with normal weight. The role of the specific adipose tissue-derived substances, called adipocytokines, in overweight- and obesity-related cardiovascular disease (CVD) is still unclear. Objective: To investigate the associations of three adipose tissue-derived substances: adiponectin, leptin, and interleukin-6 with incident CVD in a longitudinal population-based study, including extensive adjustments for traditional and metabolic risk factors closely associated with overweight and obesity. C-reactive protein (CRP) was used as a proxy for interleukin-6. Methods: Prospective population-based study of 6.502 participants, 51.9% women, aged 30-60 years, free of CVD at baseline, with a mean follow-up time of 11.4 years, equivalent to 74,123 person-years of follow-up. As outcome, we defined a composite outcome comprising of the first event of fatal and nonfatal coronary heart disease and fatal and nonfatal stroke. Results: During the follow-up period, 453 composite CV outcomes occurred among participants with complete datasets. In models, including gender, age, smoking status, systolic blood pressure, treatment for hypertension, diabetes, body mass index (BMI), total cholesterol, high-density-lipoprotein cholesterol, homeostasis model assessment of insulin resistance, estimated glomerular filtration rate, adiponectin, leptin, and CRP, neither adiponectin (hazard ratio [HR] with 95% confidence interval [CI]: 0.97 [0.87-1.08] per SD increase, P = 0.60) nor leptin (0.97 [0.85-1.12] per SD increase, P = 0.70) predicted the composite outcome, whereas CRP was significantly associated with the composite outcome (1.19 [1.07-1.35] per SD increase, P = 0.002). Furthermore, in mediation analysis, adjusted for age and sex, CRP decreased the BMI-associated CV risk by 43% (95%CI 29-72). Conclusions: In this study, neither adiponectin nor leptin were independently associated with CVD, raising questions over their role in CVD. The finding that CRP was significantly associated with an increased risk of CVD and decreased the BMI-associated CVD risk substantially, could imply that interleukin-6-related pathways may play a role in mediating overweight- and obesity-related CVD. © 2015 Seven et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
    PLoS ONE 06/2015; 10(6):e0128987. DOI:10.1371/journal.pone.0128987 · 3.23 Impact Factor
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    ABSTRACT: Objective: To study the relationship between blood pressure, circulating natriuretic peptide concentrations, gender, and pubertal stage in generally healthy adolescents. Design and method: Cross-sectional study of 15-year-old females and males (n = 335) from the Danish site of the European Youth Heart Study. Blood pressure was measured using a standardised protocol, sexual maturity was assessed according to Tanner's stages, and as a surrogate for atrial natriuretic peptide, we measured mid-regional pro-atrial natriuretic peptide in plasma. Results: Compared with boys, girls had lower systolic blood pressure (mean ± standard deviation: 109.6 ± 9.9 mm Hg vs. 116.9 ± 11.4 mm Hg, P < 0.0001) and higher plasma mid-regional pro-atrial natriuretic peptide concentrations (median (interquartile range): 42.1 pmol/L (31.9-50.2) vs. 36.6 pmol/L (30.6-44.9), P = 0.0046). When female adolescents were further subdivided according to Tanner's stages, there were no differences in blood pressure and plasma mid-regional pro-atrial natriuretic peptide concentrations between post-pubertal and pubertal girls (P > 0.17). In contrast after similar subdivision, post-pubertal boys had higher systolic blood pressure (mean ± standard deviation: 117.7 ± 11.7 mm Hg vs. 111.4 ± 7.9 mm Hg, P = 0.029) and lower plasma mid-regional pro-atrial natriuretic peptide concentrations (median (interquartile range): 36.2 pmol/L (30.6-43.1) vs. 46.4 pmol/L (30.3-51.1), P = 0.043) compared with pubertal boys. Conclusions: Given their higher systolic blood pressure, boys had lower than expected plasma concentrations of mid-regional pro-atrial natriuretic peptide compared with girls, and given their higher systolic blood pressure, post-pubertal boys had lower than expected plasma concentrations of mid-regional pro-atrial natriuretic peptide compared with pubertal boys. Therefore, our study adds to the growing body of evidence to suggest that in healthy individuals a lower circulating amount of atrial natriuretic peptide, resulting in diminished vasodilation and natriuresis, leads to higher blood pressure. Furthermore, our study provides further evidence to suggest that testosterone lowers circulating atrial natriuretic peptide concentrations, and thereby our study offers one possible explanation of why boys and younger men have higher blood pressure and higher risk of hypertension compared with girls and younger women.
    Blood pressure 05/2015; 33 Suppl 1 - ESH 2015 Abstract Book:1-6. DOI:10.3109/08037051.2015.1045703 · 1.81 Impact Factor
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    Mogens Fenger · Allan Linneberg · Jørgen Jeppesen
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    ABSTRACT: Common diseases like essential hypertension or diabetes mellitus are complex as they are polygenic in nature, such that each genetic variation only has a small influence on the disease. Genes operates in integrated networks providing the blue-print for all biological processes and conditional of the complex genotype determines the state and dynamics of any trait, which may be modified to various extent by non-genetic factors. Thus, diseases are heterogenous ensembles of conditions with a common endpoint. Numerous studies have been performed to define genes of importance for a trait or disease, but only a few genes with small effect have been identified. The major reasons for this modest progress is the unresolved heterogeneity of the regulation of blood pressure and the shortcomings of the prevailing monogenic approach to capture genetic effects in a polygenic condition. Here, a two-step procedure is presented in which physiological heterogeneity is disentangled and genetic effects are analysed by variance decomposition of genetic interactions and by an information theoretical approach including 162 single nucleotide polymorphisms (SNP) in 84 genes in the sphingolipid metabolism and related networks in blood pressure regulation. As expected, almost no genetic main effects were detected. In contrast, two-gene interactions established the entire sphingolipid metabolic and related genetic network to be highly involved in the regulation of blood pressure. The pattern of interaction clearly revealed that epistasis does not necessarily reflects the topology of the metabolic pathways i.e. the flow of metabolites. Rather, the enzymes and proteins are integrated in complex cellular substructures where communication flows between the components of the networks, which may be composite in structure. The heritabilities for diastolic and systolic blood pressure were estimated to be 0.63 +/- 0.01 , which may in fact be the maximum heritabilities of these traits.
    Frontiers in Genetics 03/2015; 6:84. DOI:10.3389/fgene.2015.00084
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    ABSTRACT: The fundamental role of inflammation in cardiovascular disease (CVD) has prompted interest in numerous biomarkers that detect subclinical levels of inflammation. Soluble urokinase plasminogen activator receptor (suPAR) is a novel biomarker that correlates significantly with cardiovascular events and outperforms traditional markers of inflammation such as C-reactive protein (CRP) in prognosticating a range of CVDs. Furthermore, of particular interest is the suggestion that suPAR reflects a pathophysiological pathway more closely linked with subclinical organ damage than CRP. We provide the first comprehensive review of suPAR in CVD and explore its function and usefulness in predicting cardiovascular events. Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
    The Canadian journal of cardiology 03/2015; DOI:10.1016/j.cjca.2015.03.023 · 3.71 Impact Factor
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    ABSTRACT: The role of the natriuretic peptides (NPs) in hypertension is complex. Thus, a higher blood NP concentration is a robust marker of pressure-induced cardiac damage in patients with hypertension, whereas genetically elevated NP concentrations are associated with a reduced risk of hypertension and overweight individuals presumably at high risk of hypertension have lower NP concentrations. To investigate the associations between serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), used as a surrogate marker for active BNP, and prevalent as well as 5-year incident hypertension in a Danish general population sample. Cross-sectional and prospective population-based study. At baseline, among 5,307 participants (51.3% women, mean age 46.0±7.9 years) with a complete set of data, we recorded 1,979 cases with prevalent hypertension (PHT). Among 2,389 normotensive participants at baseline with a complete set of data, we recorded 324 cases with incident hypertension (IHT) on follow-up 5 years later. In models adjusted for age, sex, lifestyle, social, dietary, anthropometric, pulmonic, lipid, metabolic and renal risk factors, as well as heart rate and baseline blood pressure (only incident model), one standard deviation increase in baseline log-transformed NT-proBNP concentrations was on one side associated with a 21% higher risk of PHT (odds ratio [OR]: 1.21 [95% confidence interval (CI): 1.13-1.30], P<0.001), and on the other side with a 14% lower risk of IHT (OR: 0.86 [95%CI:0.76-0.98], P = 0.020). Higher serum concentrations of NT-proBNP associate with PHT whereas lower concentrations associate with IHT. This suggests that a lower amount of circulating BNP, resulting in diminished vasodilation and natriuresis, could be involved in the pathogenesis of hypertension in its early stages.
    PLoS ONE 02/2015; 10(2):e0117864. DOI:10.1371/journal.pone.0117864 · 3.23 Impact Factor
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    ABSTRACT: The widespread use of coronary stents has exposed a growing population to the risk of stent thrombosis, but the importance in terms of risk of ST-segment elevation myocardial infarctions (STEMIs) remains unclear. We studied five years follow-up data for 2,098 all-comer patients treated with coronary stents in the randomized SORT OUT II trial (mean age 63.6 yrs. 74.8% men). Patients who following stent implantation were readmitted with STEMI were included and each patient was categorized ranging from definite- to ruled-out stent thrombosis according to the Academic Research Consortium definitions. Multivariate logistic regression was performed on selected covariates to assess odds ratios (ORs) for definite stent thrombosis. 85 patients (4.1%), mean age 62.7 years, 77.1% men, were admitted with a total of 96 STEMIs, of whom 60 (62.5%) had definite stent thrombosis. Notably, definite stent thrombosis was more frequent in female than male STEMI patients (81.8% vs. 56.8%, p = 0.09), and in very late STEMIs (p = 0.06). Female sex (OR 3.53 [1.01-12.59]) and clopidogrel (OR 4.43 [1.03-19.01]) was associated with increased for definite stent thrombosis, whereas age, time since stent implantation, use of statins, initial PCI urgency (STEMI [primary PCI], NSTEMI/unstable angina [subacute PCI] or stable angina [elective PCI]), and glucose-lowering agents did not seem to influence risk of stent thrombosis. In a contemporary cohort of coronary stented patients, stent thrombosis was evident in more than 60% of subsequent STEMIs.
    PLoS ONE 11/2014; 9(11):e113399. DOI:10.1371/journal.pone.0113399 · 3.23 Impact Factor
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    ABSTRACT: Objective: In overweight-related hypertension, the effect of weight changes on blood pressure (BP) is believed to be mediated by insulin. To test this hypothesis, we studied 5-year changes in weight, BP, and insulin in a general population of Danish adults (n = 3443; mean age 45.7 ± 7.6 years). Methods: We assessed the glucose-insulin metabolism by a standard oral glucose tolerance test. We divided the antihypertensive and antidiabetic medication-free participants into three groups: weight loss (n = 515), weight stable (n = 1778), and weight gain (n = 1150). Results: Losing on average 6.5 kg body weight, the weight loss group experienced a 28.2% reduction [(95% confidence interval [CI] -31 to -25); P < 0.001] in fasting insulin and a 23.9% reduction [(95% CI -28 to -19); P < 0.001] in 2-h insulin. Gaining on average 6.4 kg, the weight gain group experienced a 12.5% increase [(95% CI 9 to 16); P < 0.001] in fasting insulin and 32.8% increase [(95% CI 28 to 38); P < 0.001] in 2-h insulin. Using linear regression adjusting for differences in sex, age, family history of hypertension, baseline BMI, SBP and DBP, lifestyle risk factors, and their 5-year changes, weight loss was associated with a decrease in SBP of -1.8 mmHg (95% CI -2.8 to -0.7), whereas weight gain with an increase in SBP of 1.9 mmHg (95% CI 1.2 to 2.6), both with P less than 0.001. Adding fasting insulin, 2-h insulin, Δfasting insulin, and Δ2-h insulin only marginally attenuated the association, and furthermore, none of the insulin variables was significantly associated with SBP or DBP (P ≥ 0.08). The results for changes in DBP were similar to SBP. Conclusion: Five-year weight changes associate with BP alterations independent of the insulin changes.
    Journal of Hypertension 11/2014; 32(11):2231-2237. DOI:10.1097/HJH.0000000000000317 · 4.72 Impact Factor
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    ABSTRACT: Objective To investigate the influence of age and gender on the prevalence and cardiovascular disease (CVD) risk in Europeans presenting with the Metabolic Syndrome (MetS). Methods Using 36 cohorts from the MORGAM-Project with baseline between 1982–1997, 69094 men and women aged 19–78 years, without known CVD, were included. During 12.2 years of follow-up, 3.7%/2.1% of men/women died due to CVD. The corresponding percentages for fatal and nonfatal coronary heart disease (CHD) and stroke were 8.3/3.8 and 3.1/2.5. Results The prevalence of MetS, according to modified definitions of the International Diabetes Federation (IDF) and the revised National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII), increased across age groups for both genders (P<0.0001); with a 5-fold increase in women from ages 19–39 years to 60–78 years (7.4%/7.6% to 35.4%/37.6% for IDF/NCEP-ATPIII) and a 2-fold increase in men (5.3%/10.5% to 11.5%/21.8%). Using multivariate-adjusted Cox regressions, the associations between MetS and all three CVD events were significant (P<0.0001). For IDF/NCEP-ATPIII in men and women, hazard ratio (HR) for CHD was 1.60/1.62 and 1.93/2.03, for CVD mortality 1.73/1.65 and 1.77/2.06, and for stroke 1.51/1.53 and 1.58/1.77. Whereas in men the HRs for CVD events were independent of age (MetS*age, P>0.05), in women the HRs for CHD declined with age (HRs 3.23/3.98 to 1.55/1.56; MetS*age, P = 0.01/P = 0.001 for IDF/NCEP-ATPIII) while the HRs for stroke tended to increase (HRs 1.31/1.25 to 1.55/1.83; MetS*age, P>0.05). Conclusion In Europeans, both age and gender influenced the prevalence of MetS and its prognostic significance. The present results emphasise the importance of being critical of MetS in its current form as a marker of CVD especially in women, and advocate for a redefinition of MetS taking into account age especially in women.
    PLoS ONE 09/2014; 9(9):e107294. DOI:10.1371/journal.pone.0107294 · 3.23 Impact Factor
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    ABSTRACT: Mean daytime ambulatory blood pressure (BP) values are considered to be lower than conventional BP values, but data on this relation among younger individuals <50 years are scarce. Conventional and 24-hour ambulatory BP were measured in 9550 individuals not taking antihypertensive treatment from 13 population-based cohorts. We compared individual differences between daytime ambulatory and conventional BP according to 10-year age categories. Age-specific prevalences of white coat and masked hypertension were calculated. Among individuals aged 18 to 30, 30 to 40, and 40 to 50 years, mean daytime BP was significantly higher than the corresponding conventional BP (6.0, 5.2, and 4.7 mm Hg for systolic; 2.5, 2.7, and 1.7 mm Hg for diastolic BP; all P<0.0001). In individuals aged 60 to 70 and ≥70 years, conventional BP was significantly higher than daytime ambulatory BP (5.0 and 13.0 mm Hg for systolic; 2.0 and 4.2 mm Hg for diastolic BP; all P<0.0001).The prevalence of white coat hypertension exponentially increased from 2.2% to 19.5% from those aged 18 to 30 years to those aged ≥70 years, with little variation between men and women (8.0% versus 6.1%; P=0.0003). Masked hypertension was more prevalent among men (21.1% versus 11.4%; P<0.0001). The age-specific prevalences of masked hypertension were 18.2%, 27.3%, 27.8%, 20.1%, 13.6%, and 10.2% among men and 9.0%, 9.9%, 12.2%, 11.9%, 14.7%, and 12.1% among women. In conclusion, this large collaborative analysis showed that the relation between daytime ambulatory and conventional BP strongly varies by age. These findings may have implications for diagnosing hypertension and its subtypes in clinical practice.
    Hypertension 09/2014; 64(5). DOI:10.1161/HYPERTENSIONAHA.114.03957 · 6.48 Impact Factor
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    ABSTRACT: Outcome-driven recommendations about time intervals during which ambulatory blood pressure should be measured to diagnose white-coat or masked hypertension are lacking. We cross-classified 8237 untreated participants (mean age, 50.7 years; 48.4% women) enrolled in 12 population studies, using ≥140/≥90, ≥130/≥80, ≥135/≥85, and ≥120/≥70 mm Hg as hypertension thresholds for conventional, 24-hour, daytime, and nighttime blood pressure. White-coat hypertension was hypertension on conventional measurement with ambulatory normotension, the opposite condition being masked hypertension. Intervals used for classification of participants were daytime, nighttime, and 24 hours, first considered separately, and next combined as 24 hours plus daytime or plus nighttime, or plus both. Depending on time intervals chosen, white-coat and masked hypertension frequencies ranged from 6.3% to 12.5% and from 9.7% to 19.6%, respectively. During 91 046 person-years, 729 participants experienced a cardiovascular event. In multivariable analyses with normotension during all intervals of the day as reference, hazard ratios associated with white-coat hypertension progressively weakened considering daytime only (1.38; P=0.033), nighttime only (1.43; P=0.0074), 24 hours only (1.21; P=0.20), 24 hours plus daytime (1.24; P=0.18), 24 hours plus nighttime (1.15; P=0.39), and 24 hours plus daytime and nighttime (1.16; P=0.41). The hazard ratios comparing masked hypertension with normotension were all significant (P<0.0001), ranging from 1.76 to 2.03. In conclusion, identification of truly low-risk white-coat hypertension requires setting thresholds simultaneously to 24 hours, daytime, and nighttime blood pressure. Although any time interval suffices to diagnose masked hypertension, as proposed in current guidelines, full 24-hour recordings remain standard in clinical practice.
    Hypertension 08/2014; 64(5). DOI:10.1161/HYPERTENSIONAHA.114.03614 · 6.48 Impact Factor
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    ABSTRACT: Allergy is a systemic inflammatory disease that could theoretically affect the risk of cardiovascular disease (CVD) and diabetes through inflammatory pathways or mast cell-induced coronary spasm. Whether allergy is associated with an increased risk of CVD and diabetes is largely unknown. We investigated the association between atopy as assessed by IgE sensitization, a well-accepted biomarker of allergy, and incidence of ischemic heart disease, stroke, and diabetes in five Danish population-based cohorts. A total of 14,849 participants were included in the study. Atopy was defined as serum-specific IgE positivity to inhalant allergens. The Danish National Diabetes Register enabled identification of incident diabetes. Likewise, the Danish Registry of Causes of Death and the Danish National Patient Register provided information on fatal and non-fatal ischemic heart disease and stroke. Data were analyzed by Cox regression analyses with age as underlying time axis and adjusted for study cohort, gender, education, body mass index, alcohol intake, smoking habits, physical activity during leisure time, serum lipids, and blood pressure. The prevalence of atopy was 26.9 % (n = 3,994). There were 1,170, 817, and 1,063 incident cases of ischemic heart disease, stroke, and diabetes, respectively (median follow-up 11.2 years). The hazard ratios, HRs (95 % confidence intervals, CIs) for atopics versus non-atopics: for ischemic heart disease (HR 1.00, 95 % CI 0.86, 1.16), stroke (HR 1.18, 95 % CI 0.99, 1.41), and diabetes (HR 1.06, 95 % CI 0.91, 1.23). Our results did not support the hypothesis that atopy is associated with higher risk of ischemic heart disease, stroke, or diabetes. However, a small-moderately increased risk cannot be excluded from our data.
    Endocrine 06/2014; 48(2). DOI:10.1007/s12020-014-0321-z · 3.88 Impact Factor
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    ABSTRACT: Background: Data on risk associated with 24-hour ambulatory diastolic (DBP24) versus systolic (SBP24) blood pressure are scarce. Methods and results: We recorded 24-hour blood pressure and health outcomes in 8341 untreated people (mean age, 50.8 years; 46.6% women) randomly recruited from 12 populations. We computed hazard ratios (HRs) using multivariable-adjusted Cox regression. Over 11.2 years (median), 927 (11.1%) participants died, 356 (4.3%) from cardiovascular causes, and 744 (8.9%) experienced a fatal or nonfatal cardiovascular event. Isolated diastolic hypertension (DBP24≥80 mm Hg) did not increase the risk of total mortality, cardiovascular mortality, or stroke (HRs≤1.54; P≥0.18), but was associated with a higher risk of fatal combined with nonfatal cardiovascular, cardiac, or coronary events (HRs≥1.75; P≤0.0054). Isolated systolic hypertension (SBP24≥130 mm Hg) and mixed diastolic plus systolic hypertension were associated with increased risks of all aforementioned end points (P≤0.0012). Below age 50, DBP24 was the main driver of risk, reaching significance for total (HR for 1-SD increase, 2.05; P=0.0039) and cardiovascular mortality (HR, 4.07; P=0.0032) and for all cardiovascular end points combined (HR, 1.74; P=0.039) with a nonsignificant contribution of SBP24 (HR≤0.92; P≥0.068); above age 50, SBP24 predicted all end points (HR≥1.19; P≤0.0002) with a nonsignificant contribution of DBP24 (0.96≤HR≤1.14; P≥0.10). The interactions of age with SBP24 and DBP24 were significant for all cardiovascular and coronary events (P≤0.043). Conclusions: The risks conferred by DBP24 and SBP24 are age dependent. DBP24 and isolated diastolic hypertension drive coronary complications below age 50, whereas above age 50 SBP24 and isolated systolic and mixed hypertension are the predominant risk factors.
    Circulation 06/2014; 130(6). DOI:10.1161/CIRCULATIONAHA.113.004876 · 14.43 Impact Factor
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    ABSTRACT: The adipocytokines, leptin, adiponectin, and interleukin-6, which stimulate liver C-reactive protein (CRP) production, are regarded as potential candidate intermediates between adipose tissue and overweight-induced hypertension. We examined the associations between leptin, adiponectin, and CRP levels with both prevalent and 5-year incident hypertension (IHT) in a general population of Danish adults (n = 5868, 51.3% women, mean age 45.8 ± 7.9 years). We recorded 2195 prevalent and 379 incident cases of hypertension. In models including leptin, CRP, adiponectin, sex, age, lifestyle risk factors, lipids, insulin, hemoglobin A1c, and in the incident model also baseline heart rate and blood pressure, only leptin of the three candidate intermediates was significantly associated with both prevalent and IHT [odds ratio (OR) = 1.18, 95% confidence interval (CI) 1.06-1.32, P = 0.002, and OR = 1.24, 95% CI 1.01-1.54, P = 0.044] for one standard deviation increase in log-transformed leptin levels, respectively. Log-transformed CRP was associated with prevalent (OR = 1.16, 95% CI 1.07-1.26, P < 0.001) but not IHT (OR = 0.98, 95% CI 0.84-1.14, P = 0.76). Log-transformed adiponectin was neither associated with prevalent nor IHT (OR = 0.94, 95% CI 0.87-1.02, P = 0.11 and OR = 0.93, 95% CI 0.80-1.08, P = 0.33). Comparing the lowest with the highest quintile of sex-specific BMI levels, there was an almost two-fold increase in IHT (OR = 1.89, 95% CI 1.10-3.25, P = 0.023) in the fully adjusted model. The population attributable risk estimate of IHT owing to overweight was 31%. Leptin, but not adiponectin or CRP, may play a mediating role in overweight-induced hypertension. However, as BMI was a strong independent predictor of hypertension, other factors than leptin must be involved in the pathogenesis of overweight-related hypertension.
    Journal of Hypertension 05/2014; 32(7). DOI:10.1097/HJH.0000000000000207 · 4.72 Impact Factor
  • Hypertension 05/2014; 63(5):E128-E128. DOI:10.1161/HYP.0000000000000008 · 6.48 Impact Factor
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    ABSTRACT: Objectives Soluble urokinase plasminogen activator receptor (suPAR) is a marker of inflammation and endothelial dysfunction. We investigated the associations between suPAR and diabetes, including diabetes duration and complications, in patients with type 1 diabetes.Design, setting and subjectsFrom 2009 to 2011, 667 patients with type 1 diabetes and 51 non-diabetic control subjects were included in a cross-sectional study at Steno Diabetes Center, Gentofte, Denmark. suPAR levels were measured with an enzyme-linked immunosorbent assay.Main outcome measuresThe investigated diabetic complications were cardiovascular disease (CVD: previous myocardial infarction, revascularisation, peripheral arterial disease and stroke), autonomic dysfunction (heart rate variability during deep breathing <11 beats/min), albuminuria [urinary albumin excretion rate (UAER) ≥30 mg/24 h] or a high degree of arterial stiffness (pulse wave velocity ≥10 m/s). Analyses were adjusted for gender, age, systolic blood pressure, estimated glomerular filtration rate, UAER, glycated haemoglobin (HbA1c), total cholesterol, body mass index, C-reactive protein, antihypertensive treatment and smoking.ResultssuPAR levels were lower in control subjects versus all patients, in control subjects versus normoalbuminuric patients (UAER <30 mg/24 h) and in normoalbuminuric patients with short (<10 years) versus long diabetes duration, and were increased with degree of albuminuria (adjusted P < 0.001 for all). Furthermore, suPAR levels were higher in patients with versus without CVD (n = 144; 21.3%), autonomic dysfunction (n = 349; 59.2%), albuminuria (n = 357; 53.1%) and a high degree of arterial stiffness (n = 297; 47.2%) (adjusted P ≤ 0.024). The adjusted odds ratio (95% confidence interval) values per 1 ln unit increase in suPAR were: 2.5 (1.1–5.7) for CVD: 2.7 (1.2–6.2) for autonomic dysfunction; 3.8 (1.3–10.9) for albuminuria and 2.5 (1.1–6.1) for a high degree of arterial stiffness (P ≤ 0.039).Conclusion The suPAR level is higher in patients with type 1 diabetes, and is associated with diabetes duration and complications independent of other risk factors. suPAR is a potential novel risk marker for the management of diabetes.This article is protected by copyright. All rights reserved.
    Journal of Internal Medicine 05/2014; 277(3). DOI:10.1111/joim.12269 · 6.06 Impact Factor
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    ABSTRACT: Compromised autoregulation of ocular blood flow is a plausible consequence of hypertension, and studies indicate that hypertension can lead to progression of glaucoma. Initiating antihypertensive therapy in subjects with long-standing hypertension could deteriorate ocular blood flow leading ultimately to glaucomatous damage. Evidence on this topic is still equivocal but until adequate knowledge on the field has been established we recommend referral of patients disposed for glaucoma to ophthalmologic examination when initiating antihypertensive medication.
    Ugeskrift for laeger 03/2014; 176(14).
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    ABSTRACT: Low-grade chronic inflammation is a characteristic feature of obesity, the most important lifestyle risk factor for hypertension. Elevated plasma concentrations of the inflammatory biomarker C-reactive protein (CRP) are associated with an increased risk of hypertension, but elevated plasma CRP concentrations are also closely associated with obesity. It is uncertain whether CRP is directly involved in the pathogenesis of hypertension or is only a marker of other pathogenic processes closely related to obesity. We studied 103 obese men (body mass index (BMI) ≥30.0kg/m(2)); 63 of these men had 24-hour ambulatory blood pressure (ABP) ≥130/80mm Hg and comprised the obese hypertensive (OHT) group. The 40 remaining obese men had 24-hour ABP <130/80mm Hg and comprised the obese normotensive (ONT) group. Our control group comprised 27 lean normotensive (LNT) men. All participants were medication-free. We measured plasma CRP concentrations with a high-sensitivity assay and determined body composition by dual energy x-ray absorptiometry scanning. There were no differences in anthropometric measures (BMI, waist circumference, or total fat mass percentage) between OHT and ONT groups (P ≥ 0.08). The obese groups had higher CRP concentrations than the LNT group (OHT: median = 2.30, interquartile range (IQR) = 1.10-4.10mg/L; ONT: median = 2.55, IQR = 1.25-4.80mg/L; LNT: median = 0.60, IQR = 0.30-1.00mg/L; P < 0.001), but there was no difference in CRP concentrations between OHT and ONT groups (P = 1.00). In the obese men, CRP was not correlated with either 24-hour systolic (r = 0.04; P = 0.71) or 24-hour diastolic ABP (r = -0.03; P = 0.78). Obese hypertensive men, matched for anthropometric measurements, have plasma CRP concentrations similar to those of obese normotensive men.
    American Journal of Hypertension 03/2014; 27(10). DOI:10.1093/ajh/hpu029 · 2.85 Impact Factor
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    ABSTRACT: Guidelines propose classification of conventional blood pressure (CBP) into normotension (<120/<80mm Hg), prehypertension (120-139/80-89mm Hg), and hypertension (≥140/≥90mm Hg). To assess the potential differential contribution of ambulatory blood pressure (ABP) in predicting risk across CBP strata, we analyzed outcomes in 7,826 untreated people recruited from 11 populations. During an 11.3-year period, 809 participants died (276 cardiovascular deaths) and 639, 383, and 225 experienced a cardiovascular, cardiac, or cerebrovascular event. Compared with normotension (n = 2,639), prehypertension (n = 3,076) carried higher risk (P ≤ 0.015) of cardiovascular (+41%) and cerebrovascular (+92%) endpoints; compared with hypertension (n = 2,111) prehypertension entailed lower risk (P ≤ 0.005) of total mortality (-14%) and cardiovascular mortality (-29%) and of cardiovascular (-34%), cardiac (-33%), or cerebrovascular (-47%) events. Multivariable-adjusted hazard ratios (HRs) for stroke associated with 24-hour and daytime diastolic ABP (+5mm Hg) were higher (P ≤ 0.045) in normotension than in prehypertension and hypertension (1.98 vs.1.19 vs.1.28 and 1.73 vs.1.09 vs. 1.24, respectively) with similar trends (0.03 ≤ P ≤ 0.11) for systolic ABP (+10mm Hg). However, HRs for fatal endpoints and cardiac events associated with ABP did not differ significantly (P ≥ 0.13) across CBP categories. Of normotensive and prehypertensive participants, 7.5% and 29.3% had masked hypertension (daytime ABP ≥135/≥85mm Hg). Compared with true normotension (P ≤ 0.01), HRs for stroke were 3.02 in normotension and 2.97 in prehypertension associated with masked hypertension with no difference between the latter two conditions (P = 0.93). ABP refines risk stratification in normotension and prehypertension mainly by enabling the diagnosis of masked hypertension.
    American Journal of Hypertension 02/2014; 27(7). DOI:10.1093/ajh/hpu002 · 2.85 Impact Factor

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3k Citations
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  • 2003–2015
    • Glostrup Hospital
      • • Department of Cardiology
      • • Department of Medicine
      • • Department of Internal Medicine
      Glostrup, Capital Region, Denmark
  • 2009–2014
    • IT University of Copenhagen
      København, Capital Region, Denmark
    • Universidad de Montevideo
      Ciudad de Montevideo, Montevideo, Uruguay
  • 2007–2014
    • Copenhagen University Hospital
      København, Capital Region, Denmark
  • 2013
    • Aalborg University
      Ålborg, North Denmark, Denmark
  • 2008
    • Copenhagen University Hospital Hvidovre
      Hvidovre, Capital Region, Denmark
  • 2005
    • Bispebjerg Hospital, Copenhagen University
      • Department of Cardiology
      København, Capital Region, Denmark
  • 1997
    • Canterbury District Health Board
      Christchurch, Canterbury, New Zealand