Exercise systolic blood pressure at moderate workload predicts cardiovascular disease and mortality through 35 years of follow-up in healthy, middle-aged men.

OBJECTIVE: There is an association between exercise systolic blood pressure (SBP) and cardiovascular disease and mortality. The aim of this study was to investigate this association, with 35 years of follow-up. METHODS: Through 1972-75, 2014 healthy, middle-aged men underwent thorough medical examination and a bicycle exercise test. 1999 participants completed six minutes at 100 W. SBP was measured manually, both before the test and every two minutes during the test. Highest SBP measured during the first six minutes (SBP100W) was used in further analyses. RESULTS: Participants were divided into quartiles (Q) based on their SBP100W; Q1: 100-160 mm Hg (n = 457), Q2: 165-175 mm Hg (n = 508), Q3: 180-195 mm Hg (n = 545) and Q4: 200-275 mm Hg (n = 489). After 35-years follow-up, there was a significant association between exercise SBP at baseline and cardiovascular disease and mortality. In the multivariate analysis adjusting for resting SBP, age, smoking status, total serum cholesterol and family history of coronary heart disease, as well as physical fitness, there is a 1.39-fold (CI: 1.00-1.93, p = 0.05) increased risk of cardiovascular mortality in Q4 compared to Q1. When not adjusting for physical fitness, there is a 1.29-fold (CI: 1.03-1.61, p = 0.02) increase in risk of cardiovascular disease between Q1 and Q4. CONCLUSIONS: The results of this study suggest that the association between exercise SBP at moderate workload and cardiovascular disease and mortality in middle-aged men extends through as long as 35 years and into old ages.

Achievements in congenital heart defect surgery: a prospective, 40-year study of 7038 patients.

BACKGROUND: This article presents an update of the results achieved by modern surgery in congenital heart defects (CHDs) over the past 40 years regarding survival and the need for reoperations, especially focusing on the results from the past 2 decades. METHODS AND RESULTS: From 1971 to 2011, all 7038 patients <16 years of age undergoing surgical treatment for CHD at Rikshospitalet (Oslo, Norway) were enrolled prospectively. CHD diagnosis, date, and type of all operations were recorded, as was all-cause mortality until December 31, 2012. CHDs were classified as simple (3751/7038=53.2%), complex (2918/7038=41.5%), or miscellaneous (369/7037=5.2%). Parallel to a marked, sequential increase in operations for complex defects, median age at first operation decreased from 1.6 years in 1971 to 1979 to 0.19 years in 2000 to 2011. In total, 1033 died before January 1, 2013. Cumulative survival until 16 years of age in complex CHD operated on in 1971 to 1989 versus 1990 to 2011 was 62.4% versus 86.9% (P<0.0001). In the comparison of patients operated on in 2000 to 2004 versus 2005 to 2011, 1-year survival was 90.7% versus 96.5% (P=0.003), and 5-year cumulative survival was 88.8% versus 95.0% (P=0.0003). In simple versus complex defects, 434 (11.6%) versus 985 (33.8%) patients needed at least 1 reoperation before 16 years of age. In complex defects, 5-year cumulative freedom of reoperation among patients operated on in 1990 to 1999 versus 2000 to 2011 was 66% versus 73% (P=0.0001). CONCLUSIONS: Highly significant, sequential improvements in survival and reductions in reoperations after CHD surgery were seen. A future challenge is to find methods to reduce the need for reoperations and further reduce long-term mortality.

A novel ECG-index for prediction of ventricular arrhythmias in patients after myocardial infarction.

BACKGROUND: Risk prediction of ventricular arrhythmias after myocardial infarction (MI) is still insufficient. Prolonged QTc is a known risk marker of mortality and ventricular arrhythmias. QTc has not achieved clinical importance in predicting arrhythmic events in patients after MI. Recent studies have displayed that the terminal part of the QT-interval, Tpeak to Tend (TpTe), may be a more promising predictor of adverse outcome. Herein, we assessed whether TpTe may serve as a predictor of ventricular arrhythmias in patients with previous MI fulfilling current implantable cardioverter-defibrillator (ICD) indications. METHODS: Seventy-six patients with previous MI eligible for ICD therapy were prospectively enrolled. ECG measurements at baseline were recorded using a 12-lead ECG with 50 mm/s paper speed. TpTe was measured from peak of the T wave to end of T wave. Events during follow up were defined as ventricular arrhythmias requiring appropriate ICD therapy, including antitachycardia pacing and shock. RESULTS: During 23 ± 19 months, arrhythmic events occurred in 36 (47%) patients. TpTe was longer in ICD patients with recorded ventricular arrhythmias compared with those without (116 ± 26 ms vs. 102 ± 20 ms; P = 0.01), whereas ejection fraction (EF) at baseline did not differ (35 ± 9% vs. 35 ± 11%; P = 0.87). TpTe was an independent predictor of ventricular arrhythmias when adjusted for age, EF and QRS duration (HR 1.16; 95% CI 1.03-1.31; P = 0.02). CONCLUSIONS: TpTe predicted malignant arrhythmias in patients after MI independently of EF. TpTe may contribute in the risk stratification of patients to identify post-MI patients disposed to malignant arrhythmias and their need of ICD therapy.

Intra-aortic balloon pump treatment in an adult patient with a Fontan circulation and acute heart failure: a case report.

Background: There is limited evidence for the use of an intra-aortic balloon pump (IABP) in adult patients with a total cavopulmonary, or Fontan circulation. Case summary: A patient in his twenties with a Fontan circulation presented with sepsis, pneumonia, and pulmonary oedema. He was born with a hypoplastic left ventricle, atrioventricular septal defect, and hypoplastic aortic arch, and a total cavopulmonary circulation had been established within his first years of life. Standard of care treatment with antibiotics, non-invasive ventilatory support, loop diuretics, and vasopressors was initiated. Due to persistent pulmonary congestion and increasing general fatigue, an IABP was placed via a femoral artery to offload the failing systemic ventricle. Secondary to IABP treatment, mean arterial pressure rose, and vasodilatory nitroprusside could be introduced. Over 4 days of IABP treatment, the patient's general condition and ventricular systolic function improved significantly. Discussion: This case suggests that IABP treatment was important in the recovery of our patient with a Fontan circulation, pneumonia, and heart failure. We propose that during IABP treatment, an increase in stroke volume and a reduction in ventricular filling pressure is achieved, thereby increasing the transpulmonary pressure gradient that is central to pulmonary blood flow in Fontan patients. More definitive evidence is necessary to confirm our hypotheses.

Preoperative versus postoperative survival in patients with univentricular heart: a nationwide, retrospective study of patients born in 1990-2015.

OBJECTIVES: Few data exist on mortality among patients with univentricular heart (UVH) before surgery. Our aim was to explore the results of intention to perform surgery by estimating preoperative vs postoperative survival in different UVH subgroups. DESIGN: Retrospective. SETTING: Tertiary centre for congenital cardiology and congenital heart surgery. PARTICIPANTS: All 595 Norwegian children with UVH born alive from 1990 to 2015, followed until 31 December 2020. RESULTS: One quarter (151/595; 25.4%) were not operated. Among these, only two survived, and 125/149 (83.9%) died within 1 month. Reasons for not operating were that surgery was not feasible in 31.1%, preoperative complications in 25.2%, general health issues in 23.2% and parental decision in 20.5%. In total, 327/595 (55.0%) died; 283/327 (86.5%) already died during the first 2 years of life. Preoperative survival varied widely among the UVH subgroups, ranging from 40/65 (61.5%) among patients with unbalanced atrioventricular septal defect to 39/42 (92.9%) among patients with double inlet left ventricle. Postoperative survival followed a similar pattern. Postoperative survival among patients with hypoplastic left heart syndrome (HLHS) improved significantly (5-year survival, 42.5% vs 75.3% among patients born in 1990-2002 vs 2003-2015; p<0.0001), but not among non-HLHS patients (65.7% vs 72.6%; p=0.22)-among whom several subgroups had a poor prognosis similar to HLHS. A total of 291/595 patients (48.9%) had Fontan surgery CONCLUSIONS: Surgery was refrained in one quarter of the patients, among whom almost all died shortly after birth. Long-term prognosis was largely determined during the first 2 years. There was a strong concordance between preoperative and postoperative survival. HLHS survival was improved, but non-HLHS survival did not change significantly. This study demonstrates the complications and outcomes encountering newborns with UVH at all major stages of preoperative and operative treatment.

The terminal part of the QT interval (T peak to T end): a predictor of mortality after acute myocardial infarction.

BACKGROUND: The terminal part of the QT interval (T peak to T end; Tp-e)-an index for dispersion of cardiac repolarization-is often prolonged in patients experiencing malignant ventricular arrhythmias after acute myocardial infarction (AMI). We wanted to explore whether high Tp-e might predict mortality or fatal arrhythmia post-AMI. METHODS: Tp-e was measured prospectively in 1359/1384 (98.2%) consecutive patients with ST elevation (n = 525) or non-ST elevation (n = 859) myocardial infarction (STEMI or NSTEMI) admitted for coronary angiography. RESULTS: Tp-e was significantly correlated with age, heart rate (HR), heart failure, LVEF, creatinine, three-vessel disease, previous AMI and QRS and QT duration. During a mean follow-up of 1.3 years (range 0.4-2.3),109 patients (7.9%) died; 25, 45, and 39 from cardiac arrhythmia, nonarrhythmic cardiac causes and other causes, respectively. Long Tp-e was strongly associated with increased risk of death, and Tp-e remained a significant predictor of death in multivariable Cox analyses (RR 1.5, 95% CI[1.3-1.7]). HR-corrected Tp-e (cTp-e) was the strongest predictor of death (RR 1.6 [1.4-1.9]). Tp-e and cTp-e were particularly strong predictors of fatal cardiac arrhythmia (RR 1.6 [1.2-2.1] and RR 1.8 [1.4-2.4]). Findings were similar in STEMI and NSTEMI. When comparing two methods for measuring Tp-e, one including the tail of the T wave and one not, the former had markedly higher predictive power (P < 0.001). CONCLUSION: Tp-e, and in particular cTp-e, were strong predictors of mortality during the first year post-AMI, and should be further evaluated as prognostic factors additional to established post-AMI risk factors.

Sequential ADP-stimulated light transmission and multiple electrode aggregometry in patients taking aspirin and clopidogrel after non ST-elevation myocardial infarction.

BACKGROUND: Fast platelet function tests can identify weak clopidogrel responders, but data on variability over time in clopidogrel responsiveness in several clinical settings are lacking. We wanted to explore long-term variability of multiple electrode aggregometry (MEA) measurements and the agreement between MEA and light transmission aggregometry (LTA) in patients with non-ST elevation myocardial infarction (NSTEMI) treated with aspirin and clopidogrel. METHODS: Parallel MEA and LTA were performed at baseline and after 6 and 12 weeks in 31 patients treated with percutaneous coronary intervention after NSTEMI. Adenosine diphosphate (ADP) concentrations 2 µM, 6.5 µM and 10 µM were used. Parallel testings in both arterial and venous blood were performed at baseline. MEA and LTA cut-off levels were applied to discriminate aggregation values suggesting presence or absence of high platelet reactivity (HPR). RESULTS: Arterial and venous MEA and LTA aggregation were similar. Within-subject variability in both MEA and LTA aggregation throughout the study was moderate. According to MEA, eight patients had HPR at baseline (MEA aggregation > 47 U). Defining > 47% as the LTA aggregation HPR cut-off level, the same number of patients (eight) had HPR according to LTA. Of the 93 MEA/LTA observations 81 (87.1%) gave the same HPR classification. MEA vs. LTA agreement at baseline was slightly inferior to that obtained after 12 weeks. CONCLUSIONS: MEA and LTA aggregation in arterial and venous blood seem similar. Within-subject variability over time was moderate, and the agreement between LTA and MEA was good, and stable in most patients.

Long-term follow-up and sex differences in adults operated for tetralogy of Fallot.

OBJECTIVE: Adults operated for tetralogy of Fallot (TOF) have high risk of ventricular arrhythmias (VA). QRS duration >180 ms is an established risk factor for VA. We aimed to investigate heart function, prevalence of arrhythmias and sex differences in patients with TOF at long-term follow-up. METHODS: We included TOF-operated patients≥18 years from our centre's registry. We reviewed medical records and the most recent echocardiographic exam. VA was recorded on ECGs, 24-hour Holter registrations and from implantable cardioverter defibrillator. RESULTS: We included 148 patients (age 37±10 years). Left ventricular global longitudinal strain (LV GLS, -15.8±3.1% vs -18.8±3.2%, p=0.001) and right ventricular (RV) GLS (-15.8±3.9% vs -19.1±4.1%, p=0.001) were lower in men at all ages compared with women. Higher RV D1 (4.3±0.5 cm vs 4.6±0.6 cm, p=0.01), lower ejection fraction (55%±8% vs 50%±9%, p=0.02), lower RV GLS (-18.1±4.0 ms vs -16.1±4.8 ms, p=0.04) and N-terminal pro-brain natriuretic peptide (NT-proBNP) over reference range (n=27 (23%) vs n=8 (77%), p<0.001) were associated with higher incidence of VA. QRS duration was longer in men (151±30 ms vs 128±25 ms, p<0.001). No patients had QRS duration >180 ms. QRS duration did not differ in those with and without VA (143±32 ms vs 137±28 ms, p=0.06). CONCLUSIONS: Our results confirmed reduced RV function in adults operated for TOF. Male patients had impaired LV and RV function expressed by lower LV and RV GLS values at all ages. Reduced cardiac function and elevated NT-proBNP were associated with higher incidence of VA and may be important in risk assessment.

Impact of pregnancy and risk factors for ventricular arrhythmias in women with tetralogy of Fallot.

OBJECTIVE: Patients with tetralogy of Fallot (TOF) have high survival rates 30 years after surgical repair. Many patients experience pregnancy; however, the effects of pregnancy on the long-term cardiovascular outcome are not well known. We investigated the association of pregnancy and cardiac function with occurrence of ventricular arrhythmia (VA) in women with TOF. METHODS: We recruited 80 women with repaired TOF from the national database. Holter monitoring or implanted devices detected VA, defined as non-sustained or sustained ventricular tachycardia or aborted cardiac arrest. All patients underwent echocardiography. Blood tests included NT-proBNP (N-terminal pro-brain natriuretic peptide). RESULTS: 55 (69%) women had experienced pregnancy. Mean age was lower in nulliparous compared with those with children (30±9 vs 40±9, p<0.01).VA had occurred in 17 (21%) women. Prevalence of VA was higher in women who had experienced pregnancy (n=16, 94%) compared with nulliparous (n=1, 6%) (p=0.02), also when adjusted for age (OR 12.9 (95% CI 1.5 to 113.2), p=0.02).Right ventricular mechanical dispersion was more pronounced in patients with VA (50±8 ms vs 39±14 ms, p=0.01, age-adjusted OR 2.1 (95% CI 1.3 to 7.5), p=0.01). NT-proBNP was also a marker of VA (211 ng/L (127 to 836) vs 139 ng/L (30 to 465), p=0.007). NT-proBNP >321 ng/L (normal values <170 ng/L) detected women with VA (p=0.019), also independent of age (OR 7.2 (95% CI 1.7 to 30.1), p=0.007). CONCLUSION: Pregnancy was associated with higher prevalence of VA among women with TOF. Right ventricular mechanical dispersion and NT-proBNP were age-independent markers of VA. These may have importance for pregnancy counselling and risk stratification.

The Oslo Ischaemia Study: cohort profile.

PURPOSE: The Oslo Ischaemia Study was designed to investigate the prevalence and predictors of silent coronary disease in Norwegian middle-aged men, specifically validating exercise electrocardiography (ECG) findings compared with angiography. The study has been important in investigating long-term predictors of cardiovascular morbidity and mortality, as well as investigating a broad spectrum of epidemiological and public health perspectives. PARTICIPANTS: In 1972-1975, 2014 healthy men, 40-59 years old, were enrolled in the study. Comprehensive clinical examination included an ECG-monitored exercise test at baseline and follow-ups. The cohort has been re-examined four times during 20 years. Linkage to health records and national health registries has ensured complete endpoint registration of morbidity until the end of 2006, and cancer and mortality until the end of 2017. FINDINGS TO DATE: The early study results provided new evidence, as many participants with a positive exercise ECG, but no chest pain ('silent ischaemia'), did not have significant coronary artery stenosis after all. Still, they were over-represented with coronary disease after years of follow-up. Furthermore, participants with the highest physical fitness had lower risk of cardiovascular disease, and the magnitude of blood pressure responses to moderate exercise was shown to influence the risk of cardiovascular disease and mortality. With time, follow-up data allowed the scope of research to expand into other fields of medicine, with the aim of investigating predictors and the importance of lifestyle and risk factors. FUTURE PLANS: Recently, the Oslo Ischaemia Study has been found worthy, as the first scientific study, to be preserved by The National Archives of Norway. All the study material will be digitised, free to use and accessible for all. In 2030, the Oslo Ischaemia Study will be linked to the Norwegian Cause of Death Registry to obtain complete follow-up to death. Thus, a broad spectrum of additional opportunities opens.

Interaction between inflammation and blood viscosity predicts cardiovascular mortality.

OBJECTIVES: Inflammation and increased blood viscosity are associated with increased risk of cardiovascular mortality. Erythrocyte sedimentation rate (ESR) and hematocrit both influence blood viscosity whereas the first also is a marker of inflammation. We aimed to investigate ESR, hematocrit and the interaction between them as predictors of cardiovascular mortality during 26 years follow-up among healthy middle aged men. DESIGN: Four hundred and eighty eight men aged 40-59 were extensively examined in 1972-1975 and followed over a period of 26 years. Risk estimation was made in Cox proportional hazards and adjusted for age, smoking, systolic blood pressure, total serum cholesterol, and physical fitness. RESULTS: A 2.44-fold (95% CI 1.37-4.35) adjusted risk of cardiovascular mortality was found in the highest quartile of hematocrit compared to the lowest. Among the 265 men who had an ESR <6 mm/h (median), the adjusted risk of cardiovascular mortality was 3.05-fold (95% CI 1.49-6.23) in the highest quartile of hematocrit compared to the lowest. This association was not observed among the 223 men with ESR <6 mm/h. CONCLUSION: Elevated hematocrit is independently associated with increased long-term risk of cardiovascular mortality in men with high ESR. Our data suggest that the combination of inflammation and blood viscosity may improve the prediction of cardiovascular risk.

Variability in aggregometry response before and after initiation of clopidogrel therapy.

BACKGROUND: Evaluation of clopidogrel therapy by in vitro methods has limitations which may be of clinical importance. We wanted to explore the variability in aggregometry response in aspirin sensitive patients before and after initiation of clopidogrel therapy. METHODS: ADP 9.37 microM, AA 1.2mM and TRAP 25 mM stimulated light transmissions aggregometry (LTA) were performed twice before (Exams 1 and 2; 3 weeks apart)-and within one year after-initiation of clopidogrel therapy (Exam 3) in 79 patients treated with PCI. Repeated ADP aggregometry was also performed in 16 healthy volunteers in order to estimate LTA measurement error. RESULT: Inter-individual differences in ADP aggregation e.g. at Exam 1 were substantial (range 17-77%, SD 15.8%). Intra-individual changes between Exams 1 and 2 were significant (-27 to +36%, SD 14.6%, p<0.05). Inter-individual differences at Exam 3 (on clopidogrel treatment) were larger than expected from Exams 1 and 2 (p<0.01). AA aggregation was the same before and during clopidogrel treatment. In controls, inter-individual differences were smaller at ADP 10 than at ADP 5 microM. CONCLUSIONS: Inter-individual differences in ADP aggregation were significant both before and during clopidogrel therapy, and there were significant intra-individual variations over time. Therefore, prediction of aggregometry response before or during clopidogrel therapy based on single tests may be unreliable. Inter-individual differences in healthy controls are smaller at high concentrations of ADP, and comparisons of aggregometry response should be performed with caution unless ADP concentrations are standardized.

Dysfunction of the systemic right ventricle after atrial switch: physiological implications of altered septal geometry and load.

Atrial switch operation in patients with transposition of the great arteries (TGA) leads to leftward shift and changes the geometry of the interventricular septum. By including the implications of regional work and septal curvature, this study investigates if changes in septal function and geometry contribute to reduced function of the systemic right ventricle (RV) in adult TGA patients. Regional myocardial work estimation has been possible by applying a recently developed method for noninvasive work calculation based on echocardiography. In 14 TGA patients (32 ± 6 yr, means ± SD) and 14 healthy controls, systemic ventricular systolic strains were measured by speckle tracking echocardiography and regional work was calculated by pressure-strain analysis. In TGA patients, septal longitudinal strain was reduced to -14 ± 2 vs. -20 ± 2% in controls ( P < 0.01) and septal work was reduced from 2,046 ± 318 to 1,146 ± 260 mmHg·% ( P < 0.01). Septal circumferential strain measured in a subgroup of patients was reduced to -11 ± 3 vs. -27 ± 3% in controls ( P < 0.01), and a reduction of septal work (540 ± 273 vs. 2,663 ± 459 mmHg·%) was seen ( P < 0.01). These reductions were in part attributed to elevated afterload due to increased radius of curvature of the leftward shifted septum. To conclude, in this mechanistic study we demonstrate that septal dysfunction contributes to failure of the systemic RV after atrial switch in TGA patients. This is potentially a long-term response to increased afterload due to a flatter septum and suggests that medical therapy that counteracts septal flattening may improve function of the systemic RV. NEW & NOTEWORTHY We have demonstrated that transposition of the great arteries patients with systemic right ventricles (RVs) have reduced function of the interventricular septum (IVS). Since the IVS is constructed to eject into the systemic circulation, it may seem unexpected that it does not maintain function when being part of the systemic RV. By applying the principles of regional work, wall tension, and geometry, we have identified unfavorable working conditions for the IVS when the RV adapts to systemic pressures.

Survival in patients with univentricular hearts: the impact of right versus left ventricular morphology.

Objective: Patients with univentricular hearts (UVH) have high mortality despite modern treatment, and better methods to identify patients at highest risk are needed. We wanted to improve risk stratification in patients with UVH by focusing on the prognostic significance of single right versus single left ventricular morphology (SRV vs SLV). Methods: All 395 patients with UVH operated at our centre were prospectively included from 1972 to 2016 (195 SRV, 166 SLV, 34 mixed or indeterminate ventricular morphology). Diagnoses, UVH morphology, types of all operations and time and causes of death or heart transplantation (HTX) were recorded. The primary endpoint was death or HTX. Results: Among the 111 non-Fontan patients, 88 died (SRV 62 vs SLV 20; p<0.0001), 32 due to heart failure (SRV 23 vs SLV 5; p=0.0012). Twenty-five years of cumulative SRV versus SLV survival among the 284 Fontan patients (41 deaths/HTX) was 66.9% vs 87.9% (p=0.0027), partly explained by more deaths/HTX due to heart failure among patients with SRV (p=0.0006). Survival in patients with SRV with and without hypoplastic left heart syndrome (HLHS) was similar. SRV versus SLV was a strong predictor of death/HTX in multivariable proportional hazards analyses (RR 3.3, 95% CI 1.6 to 6.6). Conclusion: SRV versus SLV is a strong short-term and long-term predictor of survival among patients with UVH, mainly explained by higher rates of death/HTX due to heart failure in the SRV group. Our findings apply to patients with SRV both with and without HLHS.

Heart rate reserve predicts cardiovascular death among physically unfit but otherwise healthy middle-aged men: a 35-year follow-up study.

BACKGROUND: Heart rate reserve (HRR) has been reported to be inversely associated with cardiovascular (CV) disease and death. The impact of physical fitness (PF) on this relationship has not, however, been described in detail. We investigated how different levels of PF influenced the association between HRR and CV death during a 35-year follow-up. METHODS AND RESULTS: HRR and PF were measured in 2014 apparently healthy, middle-aged men during a symptom-limited bicycle exercise test in 1972-75. The men were divided into tertiles (T1-T3) by age-adjusted HRR. Morbidity and mortality data were registered from hospital charts through 2007 and the Norwegian Cause of Death Registry. Adjusted Cox proportional hazard regression models were used to calculate risks. Incidence of CV death was 528 (26%) during median 30 years of follow-up. Men with the lowest HRR had 41% (HR 1.41 [1.14-1.75]) increased risk of CV death compared with the men with the highest. We found a significant interaction between age-adjusted PF and HRR. After stratifying the men by PF, results were statistically significant only among men with the lowest PF, where the men with lowest HRR had a 70% (HR 1.70 [1.12-2.67]) increased risk of CV death compared with the men with the highest. CONCLUSIONS: Low HRR was independently associated with increased risk of CV death in apparently healthy, middle-aged men. The predictive impact of HRR on CV death risk was, however, confined to unfit men.

Fasting blood glucose is independently associated with resting and exercise blood pressures and development of elevated blood pressure.

OBJECTIVE: To assess whether fasting blood glucose is independently related to blood pressure at rest and during exercise, and to development of elevated blood pressure. DESIGN: Cross-sectional and prospective cohort study of 2014 apparently healthy middle-aged men. METHODS: The baseline survey included carefully standardized blood pressure measurements at rest and during exercise testing, an intravenous glucose tolerance test and a panel of fasting blood tests, including fasting blood glucose. Results from 7-years follow-up provided data on development of elevated blood pressure. RESULTS: Strong associations were found between quartiles of fasting blood glucose and baseline resting and/or exercise levels of blood pressure, and also development of elevated blood pressure over 7 years. Physical fitness, calculated from an exercise test, had a strong modulating effect on blood pressure at all levels of fasting blood glucose. In multivariate models - after adjusting for intravenous glucose tolerance, physical fitness, age, body mass index, triglycerides and cholesterol - fasting blood glucose was strongly associated with blood pressure at rest (coefficient = 2.83, P = 0.0004) and during exercise (coefficient = 6.57, P < 0.0001), and further to development of treated hypertension and/or elevated blood pressure [odds ratio (OR), 1.17; 95% confidence interval (CI), 1.05-1.31]. CONCLUSION: In healthy non-diabetic and non-hypertensive men, strong associations were found between fasting blood glucose and blood pressure at rest and during exercise and to development of elevated blood pressure after 7-years follow-up. Fasting glucose metabolism deserves scrutiny when studying the pathogenesis of hypertension.

[Exercise ECG]. / Arbeids-EKG.

Exercise ECG testing is the most widely used method for detecting myocardial ischaemia, but the test is also applied in numerous other settings. The method requires close attention to technical details and application of appropriate test protocols. Attention to absolute and relative contraindications and criteria for test abortion is mandatory. In addition to the ECG, work capacity, heart rate and blood pressure responses are also important diagnostic and prognostic markers. Interpretation of the test results depends on the setting; knowledge of potential confounders is important. The diagnostic and prognostic value of the test is population-dependent. Exercise ECG testing is most valuable as a diagnostic tool for myocardial ischaemia when pretest disease probability is high.

Seven-year increase in exercise systolic blood pressure at moderate workload predicts long-term risk of coronary heart disease and mortality in healthy middle-aged men.

Exercise systolic blood pressure (SBP) predicts coronary heart disease (CHD) in the general population. We tested whether changes in exercise SBP during 7 years predict CHD (including angina pectoris, nonfatal myocardial infarction, and fatal CHD) and mortality over the following 28 years. Peak SBP at 100 W workload (=5.5 METS [metabolic equivalents]; completed by all participants) was measured among 1392 apparently healthy men in 1972-75 and repeated in 1979-82. The men were divided into quartiles (Q1-Q4) of exercise SBP change. Relative risks were calculated using Cox proportional hazard regression adjusting for family history of CHD, age, smoking status, resting SBP, peak SBP at 100 W, total cholesterol at first examination (model 1), and further for physical fitness and change in physical fitness (model 2). The highest quartile, Q4, was associated with a 1.55-fold (95% confidence interval, 1.17-2.03) adjusted (model 1) risk of CHD and a 1.93-fold (1.24-3.02) risk of coronary heart death compared with the lowest, Q1. Q4 had a 1.40-fold (1.06-1.85) risk of CHD and a 1.70-fold (1.08-2.68) risk of coronary heart death using model 2. Q4 was associated with increased risk of cardiovascular death and all-cause death compared with Q1 in model 1, but not in model 2. Our results indicate that an increase in exercise SBP at 100 W over 7 years is independently associated with increased long-term risk of CHD and substantiate our previous finding that high exercise SBP is an important risk factor for CHD in healthy men.

Rapidly upsloping ST-segment on exercise ECG: a marker of reduced coronary heart disease mortality risk.

BACKGROUND: The prognostic value of an isolated J-point depression, or rapidly upsloping ST-segment, on an exercise ECG has long been assumed to be a benign variant. However, little or no data supporting this assumption may be found in the literature. Our task was to examine if a rapidly upsloping ST-segment on an exercise ECG is associated with changes in risk of dying from CHD in 2014 healthy middle-aged men followed for 35 years. METHODS: A group of healthy middle-aged men (n = 2014) participated in a cardiovascular survey. They underwent an examination programme including a symptom-limited ECG bicycle exercise test. Exercise induced ST-segments were categorised in three groups: normal ST-segment (n = 1383), rapidly upsloping (n = 401), and ST-depression (n = 230). Survival analyses were adjusted for smoking status, total cholesterol, systolic blood pressure, maximal heart rate, and physical fitness. The mean follow-up time was 35 years. RESULTS: The rapidly upsloping group had a 30% decreased risk of CHD death (hazard ratio, HR, 0.70, 95% CI 0.51-0.95) compared to the normal ST-segment group. The risk of CVD-death was numerically lower in the rapidly upsloping group (HR 0.82, 95% CI 0.65-1.04) compared to the normal ST-segment group. The ST-depression group had a 1.45-fold (HR 1.45, 95% CI 1.09-1.90) increased risk of CHD death compared to the normal ST-segment group. CONCLUSIONS: The rapidly upsloping ST-segment was a common finding (20%) on exercise ECG among healthy middle-aged men and was associated with a 30% reduced risk of dying from CHD compared to individuals with normal ST-segment. A rapidly upsloping ST-segment on exercise ECG may represent the true healthy state.

Low heart rates predict incident atrial fibrillation in healthy middle-aged men.

BACKGROUND: Low resting heart rate (HR) has been associated with atrial fibrillation (AF) in athletes. We aimed to study whether low HR at rest or during exercise testing was a predictor of AF in initially healthy middle-aged men. METHODS AND RESULTS: A total of 2014 healthy Norwegian men participated in a prospective cardiovascular survey, including a standardized bicycle exercise test in 1972 to 1975. During ≤35 years of follow-up (53,000 person-years of observation), 270 men developed incident AF, documented by scrutiny of health charts in all Norwegian hospitals. Risk estimation was analyzed with Cox proportional hazard models. Low exercise HR after 6 minutes exercise on the moderate workload of 100 W (HR100W) was a predictor of incident AF. Men with HR100W <100 beats per minute (n=260) were characterized by high physical fitness, low resting and low maximum HR, and they had 1.60-fold AF risk (95% confidence interval, 1.11-2.26) compared with men with HR100W ≥100 beats per minute when adjusted for age, systolic blood pressure, and physical fitness. Additional adjustment for relative heart volume slightly reduced the association. The subgroup of men (n=860) with hypertensive blood pressure measurements at baseline had the highest risk difference between low and high HR100W with hazard ratio 2.08 (1.19-3.45). CONCLUSIONS: Our data indicate that low exercise HR on a moderate workload is a long-term predictor of incident AF in healthy middle-aged men. Elevated baseline blood pressure substantially amplifies this risk. The present results suggest a relationship between increased vagal tone, high stroke volumes and incident AF, and particularly so in physically fit men.