Healthy Middle-aged Men Research Articles

Modest opposite associations of endogenous testosterone and oestradiol with left ventricular remodelling and function in healthy middle-aged men

In healthy middle-aged men, endogenous testosterone does not seem to increase risk for cardiovascular disease (CVD). One explanation might be a differential effect of testosterone, and another, interference with oestradiol with respect to specific cardiovascular functions. To investigate these possibilities, we evaluated in a cross-sectional population of 1223 healthy men, aged 46 (6) years, associations between endogenous testosterone, oestradiol and left ventricular structure and function (echocardiography). Testosterone was inversely associated with ejection fraction (EF) and with more sensitive systolic tissue Doppler imaging indices. Oestradiol was positively associated with EF. These associations were confirmed by linear regression analyses, and consistent for calculated free as well as for total sex steroid concentrations. Standardized regression coefficients were -0.13 for testosterone (P < 0.01) and 0.12 for oestradiol (P < 0.01) for the association with EF, in a model which included height, waist circumference, triglycerides, glucose, systolic blood pressure, drug-treated hypertension, heart rate, haematocrit, current smoking, serum sampling time, age and excessive alcohol use. The study suggests an opposite link, albeit modestly, of testosterone and oestradiol with left ventricle systolic function in healthy middle-aged men. The finding provides a partial explanation for the overall neutral effect on CVD of testosterone in healthy middle-aged men.

Omega-3 polyunsaturated fatty acids augment the muscle protein anabolic response to hyperinsulinaemia–hyperaminoacidaemia in healthy young and middle-aged men and women

Increased dietary LCn-3PUFA (long-chain n-3 polyunsaturated fatty acid) intake stimulates muscle protein anabolism in individuals who experience muscle loss due to aging or cancer cachexia. However, it is not known whether LCn-3PUFAs elicit similar anabolic effects in healthy individuals. To answer this question, we evaluated the effect of 8weeks of LCn-3PUFA supplementation (4g of Lovaza®/day) in nine 25-45-year-old healthy subjects on the rate of muscle protein synthesis (by using stable isotope-labelled tracer techniques) and the activation (phosphorylation) of elements of the mTOR (mammalian target of rapamycin)/p70S6K (p70 S6 kinase) signalling pathway during basal post-absorptive conditions and during a hyperinsulinaemic-hyperaminoacidaemic clamp. We also measured the concentrations of protein, RNA and DNA in muscle to obtain indices of the protein synthetic capacity, translational efficiency and cell size. Neither the basal muscle protein fractional synthesis rate nor basal signalling element phosphorylation changed in response to LCn-3PUFA supplementation, but the anabolic response to insulin and amino acid infusion was greater after LCn-3PUFA [i.e. the muscle protein fractional synthesis rate during insulin and amino acid infusion increased from 0.062±0.004 to 0.083±0.007%/h and the phospho-mTOR (Ser2448) and phospho-p70S6K (Thr389) levels increased by ∼50%; all P<0.05]. In addition, the muscle protein concentration and the protein/DNA ratio (i.e. muscle cell size) were both greater (P<0.05) after LCn-3PUFA supplementation. We conclude that LCn-3PUFAs have anabolic properties in healthy young and middle-aged adults.

High-Sensitivity C-Reactive Protein, Obesity, and Subclinical Atherosclerosis

There is a growing body of evidence suggesting that elevated plasma high-sensitivity C-reactive protein (hs-CRP) levels are associated with obesity, metabolic syndrome, and adverse cardiovascular disease (CVD) outcomes.1–3 See accompanying article on page 1430 The recent results of Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial4 demonstrated that the treatment with rosuvastatin, 20 mg daily, as compared with placebo, was associated with a 44% reduction in the cumulative incidence of major CVD events among 17 802 middle-aged healthy men and women with low levels of low-density lipoprotein cholesterol (ie, <130 mg/dL) but elevated hs-CRP (ie, hs-CRP ≥2 mg/L). The benefits of rosuvastatin were consistent in all subgroups evaluated.4 Overall, the results of JUPITER trial are consistent with the notion that achieving very low levels of low-density lipoprotein cholesterol and hs-CRP can enhance the benefits of statin therapy in the primary prevention of CVD. However, the results of JUPITER trial raise some important questions about the primary prevention of CVD. Should indications for statin therapy be expanded? How should measurements of hs-CRP be used? In addition, because the JUPITER trial …

Skin Advanced Glycation End Product Accumulation and Muscle Strength and Bone Quality among Adult Men

Advanced glycation end products (AGEs) are known to accumulate in skeletal muscle and bone tissues with aging or in diabetes. Recently developed non-invasive fluorometric measurement enables a simple determination of skin AGE level. Skin AGE may reflect general AGE accumulation. Because AGE accumulation is known to lead to tissue dysfunction, higher skin AGE level may be associated with decreased skeletal muscle strength and lower bone quality in apparently healthy adults. PURPOSE: To determine the relationship between skin AGE accumulation and muscle strength and quantitative ultrasound (QUS) evaluation of calcaneal bone quality among healthy Japanese middle aged men in a population-based cross sectional study. METHODS: Skin autofluorescence (AF), grip strength (n = 205), leg extension power (n = 121) and calcaneal QUS (n = 193) were measured in Japanese adult men (median [interquartile range] age, 46.0 [37.0, 56.0] years). RESULTS: After adjustment for potential confounders, the adjusted means (95% confidence interval [CI]) for grip strength across the tertiles of skin AF were 44.8 (43.3, 46.3) kg for the lowest tertile, 42.3 (40.8, 43.7) kg for the middle tertile, and 41.6 (40.1, 43.1) kg for the highest tertile (P for trend < 0.01). The adjusted geometric means (95% CI) of leg extension power across the tertiles of skin AF were 18.4 (17.1, 19.9) W/kg for the lowest tertile, 17.7 (16.4, 19.1) W/kg for the middle tertile, and 16.2 (15.0, 17.5) W/kg for the highest tertile (P for trend = 0.02). The geometric means (95%CI) for QUS across the tertiles of skin AF were 2.81 (2.75, 2.87) for the lowest skin AF, 2.81 (2.74, 2.87) for the middle skin AF, 2.66 (2.61, 2.73) for the highest skin AF (P for trend < 0.01). CONCLUSION: Among apparently healthy Japanese middle-aged men, those with higher skin AF had lower muscle strength and lower QUS, indicating a preclinical association between AGE accumulation and muscle strength and bone quality. A long-term prospective study is required to clarify the causality. Supported by a Grant-in-Aid under the "Knowledge Cluster Initiative" from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

C-Reactive Protein and Cardiovascular Diseases

C-reactive protein (CRP) is a unique risk marker and plays a role in the pathogenesis of inflammation and atherosclerosis. It is synthesized and secreted mainly by hepatocytes in response to interleukin-6 (IL-6) and either IL-1 or tumor necrosis factor-alpha. The average plasma half life of CRP is 19 hours. CRP activates complement, increases phagocytic activity of neutrophils, increases respiratory burst of neutrophils, and induces expression of adhesion molecules, synthesis of tissue factor, cytokines from monocytes and platelet aggregation. CRP is involved in development of atherosclerosis and thrombosis. High sensitive-CRP (hs-CRP) is a very novel biochemical marker. It is elevated in various conditions including: inflammation both acute and chronic, acute myocardial infarction, unstable angina, peripheral vascular diseases, diabetes, renal disease, hypertension, and cardiopulmonary bypass. A positive association has been reported between CRP levels and age, smoking, body mass, total cholesterol, lipoprotein a [Lp(a)], homocysteine and fibrinogen. It has a predictive value for the development of peripheral vascular disease, restenosis following percutaneous coronary interventions with or without stent implantation, and complications following cardiopulmonary bypass. Preprocedural high levels of plasma CRP are associated with high incidence of late adverse events (composite of cardiac death, nonfatal myocardial infarction, clinical occurrence of symptoms, progression of significant coronary lesion in vessels other then treated ones) after successful coronary stenting. Baseline levels of CRP predict risk of future myocardial infarction, and stroke in apparently healthy middle-aged men and women. CRP levels predict atherosclerotic vascular disease in patients with end-stage renal disease. Increased pretransplant CRP levels are associated with higher risk of acute rejection in transplant recipients. Various strategies to reduce the adverse effects of CRP have been discussed.

Relationships Among Hyperuricemia, Metabolic Syndrome, and Endothelial Function

We evaluated the relationship of the severity of hyperuricemia and the flow-mediated vasodilatation of the brachial artery (FMD) in patients with and without the metabolic syndrome (MetS). In a cross-sectional study, FMD was obtained in 2,732 Japanese healthy men (49 ± 8 years) who had no cardiovascular (CV) disease and were not on any medication for CV risk factors. MetS was defined according to Japanese criteria, and serum uric acid (UA) levels in the upper half of the fifth (highest) quintile range were defined as severe hyperuricemia, whereas those in the lower half of this quintile range were defined as mild hyperuricemia. Overall, the adjusted values of FMD were lower in the subjects with MetS (5.6 ± 0.1%; n = 413) than in those without MetS (6.2 ± 0.1%; n = 2,319) (P < 0.01). Among the subjects without MetS, the adjusted values of FMD were lower in both the subgroups with mild hyperuricemia and severe hyperuricemia than in the subgroup without hyperuricemia. On the contrary, among the subjects with MetS, the adjusted value of FMD was lower only in the subgroup with severe hyperuricemia (4.8 ± 0.3%) as compared with that in the group without hyperuricemia (5.7 ± 0.2%) (P < 0.05). In middle-aged healthy Japanese men without MetS, not only severe, but also mild hyperuricemia may be a significant independent risk factor for endothelial dysfunction in subjects without MetS, whereas only severe hyperuricemia (but not mild hyperuricemia) appeared to exacerbate endothelial dysfunction in similar subjects with MetS.

Increasing Leisure Time Physical Activity is Associated With Less Prevalence of the Metabolic Syndrome in Healthy Middle-Aged Men

The metabolic syndrome (MetS) is characterized by a constellation of factors that confer an increased risk for cardiovascular morbidity and mortality. It is well-known that physical activity (PA) has a protective role on cardiovascular morbidity and mortality, mainly through its favorable effects on traditional risk factors such as body mass and blood pressure (BP). We assessed the prevalence of MetS in a population-based sample of 58-year-old men with respect to leisure-time PA and also to occupational PA. The results showed an inverse linear association (P < .05) between leisure time physical activity (LTPA) and MetS in this group. In conclusion, this study suggests that PA has an important role in controlling MetS.

Selenium glycinate supplementation increases blood glutathione peroxidase activities and decreases prostate-specific antigen readings in middle-aged US men

Two concepts are often currently applied to selenium in adult men in the United States: • Intake is generally enough to maximize blood glutathione peroxidase activities. • In such men, selenium supplementation does not reduce risk of prostate cancer. In contrast to these concepts, 30 healthy middle-aged men were studied to test the following hypothesis: 6-week supplementation of 200 μg of selenium as glycinate can raise activities of 2 blood selenium enzymes and lower a marker of prostate cancer risk. The hypothesis was confirmed, in that selenium supplementation raised activities for erythrocyte and plasma glutathione peroxidase as well as lowered values for plasma prostate-specific antigen. The enzyme activity increases were not extremely large, but based on a chicken study, changes in blood glutathione peroxidase activities can reflect bigger changes in the prostate. Placebo treatment did not duplicate the selenium effects in 30 other men. In conclusion, this study suggests that US middle-aged men may not typically consume optimal amounts of selenium.

Overweight as predictor of long-term mortality among healthy, middle-aged men: A prospective cohort study

Objectives Large epidemiological studies of non-smokers have demonstrated an association between overweight during midlife and increased mortality. However, little is known about whether this association may be explained by physical fitness. Thus, we aimed to examine this association in a long-term follow-up, with adjustment for fitness. Methods We prospectively studied mortality in relation to overweight in 2014 healthy Norwegian men 40–59 years of age at enrolment in 1972–1975, and recorded cardiovascular and non-cardiovascular mortality during 25–27 years follow-up. Physical fitness was measured in a maximal exercise tolerance bicycle test. Results At baseline 717 men had overweight (body mass index 25.0–29.9) and 1221 had normal weight (body mass index < 25.0). During follow-up 746 men died, 377 from cardiovascular causes. Among non-smokers with overweight/normal weight, cardiovascular death rates were 19.4%/11.3%, and non-cardiovascular death rates were 13.2%/14.4%. Overweight was related to cardiovascular mortality, even after adjustment for age, physical fitness, blood pressure and cholesterol level (RR: 1.52, p = 0.010), but not to non-cardiovascular mortality (RR: 0.84, p = 0.32). Among smokers overweight was not associated with cardiovascular or non-cardiovascular mortality. The difference in cardiovascular mortality between non-smokers with overweight and normal weight first appeared after 15 years of follow-up. Conclusion Overweight appears to be an independent long-term predictor of cardiovascular mortality in middle-aged healthy non-smoking men, even after adjustment for physical fitness.

Influences of the Common FTO rs9939609 Variant on Inflammatory Markers Throughout a Broad Range of Body Mass Index

BackgroundA recent study reported that the fatness associated A-allele of FTO rs9939609 increased plasma high sensitivity C-reactive protein (hs-CRP) levels independent of fatness. We aimed to investigate if this gene variant had fatness-independent effects on plasma hs-CRP and 10 additional circulating obesity-related adipokines throughout a broad range of body mass index (BMI) among Danish men.Methodology/Principal FindingsIn a population of 362,200 young men, examined for military service between 1943 and 1977, two groups were identified: 1) a random 1% sample and 2) all obese men (BMI = 31.0 kg/m2, all of whom were above the 99th percentile of this population). At an average age of 49 years (range: 39 through 65 years), 551 men, hereof 231 of the obese, were re-examined, including genotyping and measurement of the fasting circulating inflammatory markers hs-CRP, IL-1β, IL-6, IL-10, IL-18, mip1α, mip1β, sTNFα-R1, TGF-β, TNF-α and leptin. Men with known disease were excluded from the examination. All the inflammatory markers were log-transformed to approximate a normal distribution. Genotype-phenotype relationships were studied using linear regression analyses with the inflammatory markers as the response variable. Significant positive associations between hs-CRP, leptin and a broad range of BMI were observed, but the associations did not significantly differ across FTO rs9939609 genotype. There were no significant associations between the other inflammatory markers, FTO rs9939609 genotype or BMI, respectively.ConclusionNo fatness-independent effects of the FTO rs9939609 A-allele on a series of inflammatory markers were observed in this cohort of healthy middle-aged men representing a broad range of fatness.

Effects of Moderate-to-Severe Impairment of the Estimated Glomerular Filtration Rate and of Proteinuria on the Central Hemodynamics and Arterial Stiffness in Middle-Aged Healthy Japanese Men

We evaluated the effects of moderate-to-severe impairment of the estimated glomerular filtration rate (eGFR: 15 to 59 mL/min per 1.73 m2) and of proteinuria on the central hemodynamics and the pulse wave velocity (PWV) in 2244 middle-aged healthy Japanese men who were not receiving any medications for cardiovascular diseases or cardiovascular risk factors. The adjusted value of the radial augmentation index was higher in the subjects with proteinuria than in those without proteinuria. On the other hand, this value was similar between the subjects with and without moderate-to-severe impairment of the eGFR. Not only proteinuria but also moderate-to-severe impairment of the eGFR was associated with increase in the adjusted value of the brachial-ankle PWV. Thus, proteinuria was found to be an independent risk factor for abnormal central hemodynamics and increased stiffness of the large- to middle-sized arteries, while moderate-to-severe impairment of the eGFR was associated with an increase of the arterial stiffness, but not with abnormality of the central hemodynamics.

Adipokines and the risk of type 2 diabetes in healthy middle-aged men: the PRIME study

An abstract is not available for this content. As you have access to this content, full HTML content is provided on this page. A PDF of this content is also available in through the ‘Save PDF’ action button.

Pomegranate juice supplementation lowers blood pressure but does not influence pulse wave velocity or antioxidant status in healthy young and middle-aged men and women

Pomegranate juice supplementation lowers blood pressure but does not influence pulse wave velocity or antioxidant status in healthy young and middle-aged men and women

Relationships between vascular calcification, calcium metabolism, bone density, and fractures

Factors involved with calcium metabolism, such as serum calcium and phosphate and calcium intake, have been associated with vascular disease in different populations. We investigated whether this association is mediated via increased vascular calcification by assessing relationships between these factors and abdominal aortic calcification (AAC) and coronary artery calcification (CAC). A total of 1471 healthy postmenopausal women participated in a 5-year randomized, placebo-controlled trial of calcium 1 g/day, and 323 healthy middle-aged and older men participated in a 2-year randomized, placebo-controlled trial of calcium 600 or 1200 mg/day. AAC was assessed on vertebral morphometric images at baseline and follow-up. Based on computed tomography, 163 men had CAC assessed, on average, 1.5 years after study completion. In elderly women, AAC was positively related to serum calcium (p < .001), phosphate (p = .04), and the calcium-phosphate product (p = .003), but changes in AAC over time and incidence of cardiovascular events were not related to these variables. In middle-aged men, AAC and CAC were not consistently related to these variables. Neither dietary calcium intake nor calcium supplementation was associated with changes in the prevalence of AAC over time, and calcium supplementation also was not related to CAC scores in men. After adjusting for age, AAC was not associated with low bone mineral density (BMD) at baseline, changes in BMD over time, or fracture incidence. CAC also was not related to baseline BMD. In summary, serum calcium and phosphate are associated with AAC in older women, but dietary calcium intake and calcium supplementation were not associated with changes in AAC over 2 to 5 years.

Changes in Waist Circumference and Mortality in Middle-Aged Men and Women

BackgroundWaist circumference (WC) adjusted for body mass index (BMI) is positively associated with mortality, but the association with changes in WC is less clear. We investigated the association between changes in WC and mortality in middle-aged men and women, and evaluated the influence from concurrent changes in BMI.Methodology/Principal FindingsData on 26,625 healthy men and women from the Danish Diet, Cancer and Health study was analyzed. WC and BMI were assessed in 1993–97 and in 1999–02. Information on mortality was obtained by linkage to the Danish central Person Register. Hazard ratios (HR) were estimated with Cox regression models. During 6.7 years of follow-up, 568 and 361 deaths occurred among men and women, respectively. Changes in WC were positively associated with mortality (HR per 5 cm for the sexes combined = 1.09 (1.02∶1.16) with adjustment for covariates, baseline WC, BMI and changes in BMI), whereas changes in BMI were inversely associated with mortality (HR per kg/m2 for the sexes combined = 0.91 (0.86, 0.97) with adjustment for covariates, baseline WC, BMI and changes in WC). Associations between changes in WC and mortality were not notably different in sub-groups stratified according to changes in BMI, baseline WC or when smokers or deaths occurring within the first years of follow-up were excluded.Conclusions/SignificanceChanges in WC were positively associated with mortality in healthy middle-aged men and women throughout the range of concurrent changes in BMI. These findings suggest a need for development of prevention and treatment strategies targeted against redistribution of fat mass towards the abdominal region.

Simple advice on lifestyle habits and long-term changes in biomarkers of inflammation and vascular adhesion in healthy middle-aged men

Lifestyle habits, vascular function and inflammation are components in the development of cardiovascular disease (CVD). We investigated whether simple advice on dietary and exercise habits given (at a single time point) to hypercholesterolemic men affects circulating biomarkers of inflammation and vascular adhesion. In total, 157 men (age 46±5 years) with mild hypercholesterolemia were randomized to four intervention groups, diet (D, n=40), exercise (E, n=39), diet and exercise (DE, n=39) or controls (C, n=39) and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1) and soluble E-selectin (sE-selectin) were quantified at baseline and after a 6-month intervention period. The intervention applied in this study, that is, simple advice on lifestyle changes given at a single time point, had a modest effect on inflammatory biomarkers and soluble vascular adhesion molecules. The most apparent alterations were found for individuals in group DE, who responded with significant reductions in sICAM-1, -28 (-41 to -14 μg/l) and sE-selectin, -3.6 (-6.9 to -0.3 μg/l) after 6 months. None of the groups had altered their concentrations of sVCAM-1, CRP or IL-6 significantly after the intervention. In all individuals combined, we found changes in apolipoprotein B (apoB) to predict alterations in sICAM-1 (β=0.21) and sE-selectin (β=0.26), independently of changes in inflammation and other adhesion molecules. These observations indicate that even small efforts to improve diet and physical activity can influence biomarkers of vascular function in individuals at increased risk for CVD. ApoB was identified as an important determinant of this improvement, which adds further support to the notion of apoB as a critical target in cardiovascular prevention.

Effect of 8 weeks resistance training on plasma visfatin in middle aged men

Visfatin, a novel adipokine, is increased in obesity. It is not well known whether resistance training induced change in adipose tissue and blood lipids decrease plasma visfatin; thus, the purpose...

Application of statistical and functional methodologies for the investigation of genetic determinants of coronary heart disease biomarkers: lipoprotein lipase genotype and plasma triglycerides as an exemplar

Genome-wide association studies have proved very successful in identifying novel single-nucleotide polymorphisms (SNPs) associated with disease or traits, but the related, functional SNP is usually unknown. In this paper, we describe a methodology to locate and validate candidate functional SNPs using lipoprotein lipase (LPL), a gene previously associated with triglyceride levels, as an exemplar. Two thousand seven hundred and eighty-six healthy middle-aged men from the NPHSII UK prospective study (with up to six measures of plasma lipid levels) were genotyped for 20 LPL tagging (t)SNPs using Illumina Bead technology. Using model-selection procedures and haplotypes, we identified eight SNPs that consistently maximized the fit of the model to the phenotype. Fifteen SNPs in high linkage disequilibrium with these were identified, and functional assays were carried out on all 23 SNPs. Electrophoretic mobility shift assay (EMSA) was used to identify SNPs that had the potential to alter DNA–protein interactions, reducing the number to eight possible candidate SNPs. These were examined for ability to alter expression using a luciferase reporter assay, and two regulatory SNPs, showing genotype differences, rs327 and rs3289, were identified. Finally, multiplexed-competitor-EMSA (MC-EMSA) and supershift EMSA identified FOXA2 to rs327T, and CREB-binding protein (CBP) and CCAAT displacement protein (CDP) to rs3289C as the factors responsible for transcription binding. We have identified two novel candidate functional SNPs in LPL and presented a procedure aimed to efficiently detect SNPs potentially causal to genetic association. We believe that this methodology could be successfully applied to future re-sequencing data.

Leisure-time physical activity, cardiovascular risk factors and mortality during a 34-year follow-up in men

The inverse relationship between physical activity and mortality may be confounded by socioeconomic factors, cardiovascular risk factors and inverse causality. We investigated long-term association between self-reported regular physical activity and mortality in a socioeconomically homogeneous, initially healthy middle-aged (mean age 47) male cohort (the Helsinki Businessmen Study). In 1974, the men were assessed with questionnaires, clinical and laboratory examinations. Cardiovascular disease (CVD) risk factors (including body mass index [BMI], age, cholesterol, glucose, systolic blood pressure and smoking) and details of physical activity of 782 men were available. Leisure time physical activity was collapsed into 3 categories: low (n = 148), moderate (n = 398) and high activity (n = 236). Physical activity was also briefly assessed in questionnaire surveys in 1985-1986 and in 2000. Total mortality up to 2007 was retrieved from the Central Population Register. Altogether 295 men (37.7%) died during the 34-year follow-up, and leisure-time physical activity was significantly related to mortality in a step-wise manner: 45.9% (n = 68), 37.7% (n = 150), and 32.6% (n = 77) died in the low, moderate, and high activity groups, respectively (P < 0.001). With high activity group as referent and adjusted for midlife CVD risk, perceived health and fitness at baseline, hazard ratio for total mortality was 1.21 (95% confidence interval: 0.90, 1.62), and 1.61 (95% confidence interval: 1.13, 2.30) in the moderate and low activity groups, respectively. During the 34-year follow-up, leisure-time physical activity in initially healthy middle-aged men had a graded association with reduced mortality that was independent of CVD risk, glucose and BMI.

SYSTOLIC BLOOD PRESSURE ABOVE 128 MMHG PREDICTS ATRIAL FIBRILLATION IN APPARENTLY HEALTHY MEN; A 35-YEAR FOLLOW-UP STUDY: 1A.06

Objective: Hypertension is the most prevalent risk factor leading to the development of atrial fibrillation, the most common cardiac arrhythmia. It is assumed that this risk increases with increasing blood pressure (BP) levels, but it is yet unknown at which level systolic BP imposes a risk for atrial fibrillation. We aimed to study baseline systolic BP and assess the risk of developing atrial fibrillation in relation to different BP quartiles. Design and Methods: From 1972–1975; 2014 apparently healthy men aged 40–59 years were included in the “Oslo Ischemia Study” and underwent a clinical examination including standardized BP measurements. After 35 year follow-up; 272 men were diagnosed with atrial fibrillation by scrutinizing all hospital charges (>90% complete follow-up). Risk estimation was analyzed using Cox proportional hazards and adjusted for age, smoking and total cholesterol. Results: The adjusted risk of developing atrial fibrillation was increased by 63% for the study participants with baseline systolic BP >128mmHg compared to participants with systolic BP <128mmHg (HR 1.63, 95% CI 1.25 – 2.14, p = 0.0003). Additional adjustments for resting heart rate, physical fitness and maximal heart rate during exercise did not influence the results. Quartile 3 with baseline systolic BP 128–138 mmHg had approximately the same risk as quartile 4 with baseline systolic BP 140–220 mmHg (Kaplan- Meier curves shown in figure). Conclusion: In apparently healthy middle-aged men systolic blood pressure >128 mmHg is a strong independent long-term predictor of atrial fibrillation.