The atorvastatin metabolite pattern in muscle tissue and blood plasma is associated with statin muscle side effects in patients with coronary heart disease; An exploratory case-control study.

Background and aims: Statin-associated muscle symptoms (SAMS) is a prevalent cause of statin discontinuation. It is challenging and time-consuming for clinicians to assess whether symptoms are caused by the statin or not, and diagnostic biomarkers are requested. Atorvastatin metabolites have been associated with SAMS. We aimed to compare atorvastatin pharmacokinetics between coronary heart disease (CHD) patients with and without clinically statin intolerance and statin-dependent histopathological alterations in muscle tissue. Secondarily we aimed to assess genetic variants relevant for the observed pharmacokinetic variables. Methods: Twenty-eight patients with CHD and subjective SAMS were included in the exploratory MUSE biomarker study in 2020. Participants received atorvastatin 40 mg/day for seven weeks followed by no statins for eight weeks. Muscle biopsies and blood were collected at the end of each period. Four patients were categorized as clinically intolerant to ≥3 statins prior to study start whereas four patients had signs of muscle cell damage during treatment. Results: We found significantly lower levels of atorvastatin acids, and higher lactone/acid ratios in the statin intolerant, both in muscle and plasma. With optimal cut-off, the combination of 2-OH-atorvastatin acid and the 2-OH-atorvastatin lactone/acid ratio provided sensitivity, specificity, and predictive values of 100 %. Patients with variants in UGT1A1 and UGT1A3 had higher lactone metabolite levels than those with wild type, both in muscle and plasma. Conclusion: Atorvastatin metabolites appear promising as biomarkers for the identification of clinical statin intolerance in patients with self-perceived SAMS, but the findings have to be confirmed in larger studies.

Atorvastatin Metabolite Pattern in Skeletal Muscle and Blood from Patients with Coronary Heart Disease and Statin-Associated Muscle Symptoms.

Self-perceived statin-associated muscle symptoms (SAMS) are prevalent, but only a minority is drug-dependent. Diagnostic biomarkers are not yet identified. The local statin exposure in skeletal muscle tissue may correlate to the adverse effects. We aimed to determine whether atorvastatin metabolites in blood reflect the corresponding metabolite levels in skeletal muscle, and whether genetic variants of statin transporters modulate this relationship. We also addressed atorvastatin metabolites as potential objective biomarkers of SAMS. Muscle symptoms were examined in patients with coronary disease and self-perceived SAMS during 7 weeks of double-blinded treatment with atorvastatin 40 mg/day and placebo in randomized order. A subset of 12 patients individually identified with more muscle symptoms on atorvastatin than placebo (confirmed SAMS) and 15 patients with no difference in muscle symptom intensity (non-SAMS) attended the present follow-up study. All received 7 weeks of treatment with atorvastatin 40 mg/day followed by 8 weeks without statins. Biopsies from the quadriceps muscle and blood plasma were collected after each treatment period. Strong correlations (rho > 0.7) between muscle and blood plasma concentrations were found for most atorvastatin metabolites. The impact of the SLCO1B1 c.521T>C (rs4149056) gene variant on atorvastatin's systemic pharmacokinetics was translated into muscle tissue. The SLCO2B1 c.395G>A (rs12422149) variant did not modulate the accumulation of atorvastatin metabolites in muscle tissue. Atorvastatin pharmacokinetics in patients with confirmed SAMS were not different from patients with non-SAMS. In conclusion, atorvastatin metabolite levels in skeletal muscle and plasma are strongly correlated, implying that plasma measurements are suitable proxies of atorvastatin exposure in muscle tissue. The relationship between atorvastatin metabolites in plasma and SAMS deserves further investigation.

Clinical and psychological factors in coronary heart disease patients with statin associated muscle side-effects.

BACKGROUND: To compare clinical and psychological factors among patients with self-perceived statin-associated muscle symptoms (SAMS), confirmed SAMS, and refuted SAMS in coronary heart disease patients (CHD). METHODS: Data were obtained from a cross-sectional study of 1100 CHD outpatients and a study of 71 CHD outpatients attending a randomized, double-blinded, placebo-controlled, crossover study to test effects of atorvastatin 40 mg/day on muscle symptom intensity. Clinical and psychosocial factors were compared between patients with and without SAMS in the cross-sectional study, and between patients with confirmed SAMS and refuted SAMS in the randomized study. RESULTS: Bilateral, symmetric muscle symptoms in the lower extremities during statin treatment were more prevalent in patients with confirmed SAMS compared to patients with refuted SAMS (75% vs. 41%, p = 0.01) in the randomized study. No significant differences in psychological factors (anxiety, depression, worry, insomnia, type D personality characteristics) were detected between patients with and without self-perceived SAMS in the cross-sectional study, or between patients with confirmed SAMS and refuted SAMS, in the randomized study. CONCLUSIONS: Patients with confirmed SAMS more often present with bilateral lower muscle symptoms compared to those with refuted SAMS. Psychological factors were not associated with self-perceived SAMS or confirmed SAMS. A careful pain history and a search for alternative causes of muscle symptoms are likely to promote communication in patients with SAMS, and may reduce the risk for statin discontinuation.

Post-myocardial infarction rehabilitation and secondary prevention in hospitals. / Rehabilitering og sekundærforebygging etter hjerteinfarkt ved sykehus.

BACKGROUND: Norwegian studies have documented poor cardiovascular risk factor control and a high incidence of new cardiovascular events in myocardial infarction patients. There is little knowledge about the scope of secondary prevention treatment and cardiac rehabilitation in Norwegian hospitals. Therefore, we wanted to conduct a survey of discharge routines and outpatient follow-up after myocardial infarction. MATERIAL AND METHOD: In October 2018, the heads of cardiology departments and nurse managers/physiotherapists at cardiology outpatient clinics at all Norwegian hospitals (N = 51) were contacted and asked to take part in a telephone interview. RESULTS: A total of 40 doctors (78 %) and 51 nurses/physiotherapists (100 %) conducted the telephone interview. Eleven hospitals used standardised discharge summary templates with treatment targets and expected follow-up. Ten hospitals offered routine outpatient follow-up. A total of 47 hospitals (92 %) offered multidisciplinary cardiac rehabilitation, 'heart school' classes or cardiac exercise training, and of these 9 (18 %) offered multidisciplinary comprehensive cardiac rehabilitation in line with international recommendations. INTERPRETATION: The survey revealed considerable differences in reported discharge routines and the provision of cardiac rehabilitation and outpatient follow-up at Norwegian hospitals.

The relationship between directly measured statin adherence, self-reported adherence measures and cholesterol levels in patients with coronary heart disease.

BACKGROUND AND AIMS: We aimed to determine the relationship between statin adherence measured directly, and by self-report measures and serum cholesterol levels. METHODS: Patients prescribed atorvastatin (N = 373) participated in a cross-sectional study 2-36 months after a coronary event. Self-reported adherence included statin adherence the past week, the 8-item Morisky medication adherence scale (MMAS-8), and the Gehi et al. adherence question. Atorvastatin was measured directly in spot blood plasma by a novel liquid chromatography tandem mass-spectrometry method discriminating adherence (0-1 doses omitted) and reduced adherence (≥2 doses omitted). Participants were unaware of the atorvastatin analyses at study participation. RESULTS: Mean age was 63 (SD 9) years and 8% had reduced atorvastatin adherence according to the direct method. In patients classified with reduced adherence by the direct method, 40% reported reduced statin adherence, 32% reported reduced adherence with the MMAS-8 and 22% with the Gehi question. In those adherent by the direct method, 96% also reported high statin adherence, 95% reported high adherence on the MMAS-8 whereas 94% reported high adherence on the Gehi question. Cohen's kappa agreement score with the direct method was 0.4 for self-reported statin adherence, 0.3 for the Gehi question and 0.2 for the MMAS-8. Adherence determined by the direct method, self-reported statin adherence last week, and the Gehi question was inversely related to LDL-cholesterol levels with a p-value of <0.001, 0.001 and 0.004, respectively. CONCLUSIONS: Plasma-statin measurements reveal reduced adherence with higher sensitivity than self-report measures, relate to cholesterol levels, and may prove to be a useful tool to improve lipid management.

Effect of atorvastatin on muscle symptoms in coronary heart disease patients with self-perceived statin muscle side effects: a randomized, double-blinded crossover trial.

AIMS: To estimate the effect of atorvastatin on muscle symptom intensity in coronary heart disease (CHD) patients with self-perceived statin-associated muscle symptoms (SAMS) and to determine the relationship to blood levels of atorvastatin and/or metabolites. METHODS AND RESULTS: A randomized multi-centre trial consecutively identified 982 patients with previous or ongoing atorvastatin treatment after a CHD event. Of these, 97 (9.9%) reported SAMS and 77 were randomized to 7-week double-blinded treatment with atorvastatin 40 mg/day and placebo in a crossover design. The primary outcome was the individual mean difference in muscle symptom intensity between the treatment periods, measured by visual-analogue scale (VAS) scores. Atorvastatin did not affect the intensity of muscle symptoms among 71 patients who completed the trial. Mean VAS difference (statin-placebo) was 0.31 (95% CI: -0.24 to 0.86). The proportion with more muscle symptoms during placebo than atorvastatin was 17% (n = 12), 55% (n = 39) had the same muscle symptom intensity during both treatment periods whereas 28% (n = 20) had more symptoms during atorvastatin than placebo (confirmed SAMS). There were no differences in clinical or pharmacogenetic characteristics between these groups. The levels of atorvastatin and/or metabolites did not correlate to muscle symptom intensity among patients with confirmed SAMS (Spearman's rho ≤0.40, for all variables). CONCLUSION: Re-challenge with high-intensity atorvastatin did not affect the intensity of muscle symptoms in CHD patients with self-perceived SAMS during previous atorvastatin therapy. There was no relationship between muscle symptoms and the systemic exposure to atorvastatin and/or its metabolites. The findings encourage an informed discussion to elucidate other causes of muscle complaints and continued statin use.

Medical and Psychosocial Factors Associated With Low Physical Activity and Increasing Exercise Level After a Coronary Event.

PURPOSE: The reasons why many coronary patients are inactive or have a low level of physical activity (PA) are not completely understood. We identified medical and psychosocial factors associated with PA status and increasing exercise level after a coronary event. METHODS: A cross-sectional study investigated the factors associated with PA in 1101 patients hospitalized with myocardial infarction (MI) and/or a revascularization procedure. Data were collected from hospital records, a self-report questionnaire, and a clinical examination. PA was categorized as inactivity, low activity, and adequate activity (≥ moderate intensity of 30 min ≥2-3 times/wk), an overall summary PA-index was measured as a continuous variable, and self-reported PA increase since the index event was measured on a 0- to 10-point Likert Scale. RESULTS: In all, 18% reported inactivity, 42% low, and 40% adequate activity at follow-up after median 16 mo. In multiadjusted linear regression analyses, low PA-index was significantly associated with smoking, obesity, unhealthy diet, depression, female, low education, MI as index diagnosis, and ≥1 previous coronary event. Motivation, risk and illness perceptions, and low reported need of help to increase PA were significantly associated with self-reported increasing PA level in adjusted continuous analyses. CONCLUSIONS: Daily smoking, obesity, unhealthy diet, and depression were the major potentially modifiable factors associated with insufficient PA, whereas high motivation and risk and illness perceptions were associated with increasing PA level. Further research on the effect of interventions tailored to the reported significant factors of failure is needed to improve PA level in CHD patients.

Optimal blood pressure control after coronary events: the challenge remains.

We identified sociodemographic, medical, and psychosocial factors associated with unfavorable blood pressure (BP) control in 1012 patients, hospitalized with myocardial infarction and/or a coronary revascularization procedure. This cross-sectional study collected data from hospital records, a comprehensive self-report questionnaire, clinical examination, and blood samples after 2-36 (mean 17) months follow-up. Forty-six percent had unfavorable BP control (≥140/90 [80 in diabetics] mm Hg) at follow-up. Low socioeconomic status and psychosocial factors did not predict unfavorable BP control. Patients with unfavorable BP used on average 1.9 (standard deviation 1.1) BP-lowering drugs at hospital discharge, and the proportion of patients treated with angiotensin inhibitors and beta-blockers decreased significantly (P < .001) from discharge to follow-up. Diabetes (odds ratio [OR] 2.4), higher body mass index (OR 1.05 per 1.0 kg/m2), and older age (OR 1.04 per year) were significantly associated with unfavorable BP control in adjusted analyses. Only age (standardized beta [ß] 0.24) and body mass index (ß 0.07) were associated with systolic BP in linear analyses. We conclude that BP control was insufficient after coronary events and associated with obesity and diabetes. Prescription of BP-lowering drugs in hypertensive patients seems suboptimal. Overweight and intensified drug treatment thus emerge as the major factors to target to improve BP control.

The role of cardiac rehabilitation in secondary prevention after coronary events.

Background Coronary risk factor control in Europe is suboptimal and there are large variations in the nature of cardiac rehabilitation (CR) programmes offered to coronary heart disease patients. We aim to explore characteristics and risk factor control in patients recruited from two neighbouring hospitals offering CR with different content. Methods In a cross-sectional study, 1127 Norwegian patients hospitalized with acute myocardial infarction and/or a revascularization procedure attended a clinical visit and completed a questionnaire at 2-36 months' follow-up. The hospital of Vestfold provides comprehensive CR, while the hospital of Drammen provides mainly exercise-based CR. Results At follow-up, patients in Vestfold performed more physical activity ( p = 0.02), were less obese ( p = 0.02) and reported better medication adherence ( p = 0.02) than patients in Drammen. The perceived need for information and follow-up was higher in Drammen than Vestfold ( p < 0.001). The CR participation rate in Vestfold was 75% compared with 18% in Drammen. CR participation in Vestfold was associated with higher prevalence of smoking cessation ( p = 0.001), lower low-density lipoprotein cholesterol ( p = 0.01) and better medication adherence ( p = 0.02) compared with non-CR, in adjusted analyses. No differences in diet, body weight, or blood pressure control were found between CR and non-CR. Conclusions Vestfold, with comprehensive CR, had a higher participation rate and more risk factors on target than Drammen. Participation in CR in Vestfold was associated with higher levels of smoking cessation and medication adherence, and lower low-density lipoprotein cholesterol, but overall risk factor control is still deficient, underlining the need for improved understanding of barriers to optimal risk factor control.

Medical and psychosocial factors and unfavourable low-density lipoprotein cholesterol control in coronary patients.

Objective Understanding the determinants of low-density lipoprotein cholesterol (LDL-C) control constitutes the basis of modelling interventions for optimal lipid control and prognosis. We aim to identify medical and psychosocial (study) factors associated with unfavourable LDL-C control in coronary patients. Methods A cross-sectional explorative study used logistic and linear regression analysis to investigate the association between study factors and LDL-C in 1095 patients, hospitalized with myocardial infarction and/or a coronary revascularization procedure. Data were collected from hospital records, a comprehensive self-report questionnaire, clinical examination and blood samples after 2-36 months follow-up. Results Fifty-seven per cent did not reach the LDL-C target of 1.8 mmol/l at follow-up. Low socioeconomic status and psychosocial factors were not associated with failure to reach the LDL-C target. Statin specific side-effects (odds ratio 3.23), low statin adherence (odds ratio 3.07), coronary artery by-pass graft operation as index treatment (odds ratio 1.95), ≥ 1 coronary event prior to the index event (odds ratio 1.81), female gender (odds ratio 1.80), moderate- or low-intensity statin therapy (odds ratio 1.62) and eating fish < 3 times/week (odds ratio 1.56) were statistically significantly associated with failure to reach the LDL-C target, in adjusted analyses. Only side-effects (standardized ß 0.180), low statin adherence ( ß 0.209) and moderate- or low-intensity statin therapy ( ß 0.228) were associated with LDL-C in continuous analyses. Conclusions Statin specific side-effects, low statin adherence and moderate- or low-intensity statin therapy were the major factors associated with unfavourable LDL-C control. Interventions to improve LDL-C should ensure adherence and prescription of sufficiently potent statins, and address side-effects appropriately.

Reproducibility of an extensive self-report questionnaire used in secondary coronary prevention.

AIMS: Self-reported information from questionnaires is frequently used in clinical epidemiological studies, but few provide information on the reproducibility of instruments applied in secondary coronary prevention studies. This study aims to assess the test-retest reproducibility of the questionnaire applied in the cross-sectional NORwegian CORonary (NOR-COR) Prevention Study. METHODS: In the NOR-COR study 1127 coronary heart disease (CHD) patients completed a self-report questionnaire consisting of 249 questions, of which there are both validated instruments and de novo questions. Test-retest reliability of the instrument was estimated after four weeks in 99 consecutive coronary patients. Intraclass Correlation Coefficient (ICC) and Kappa (κ) were calculated. RESULTS: The mean interval between test and retest was 33 (±6.4) days. Reproducibility values for questions in the first part of the questionnaire did not differ from those in the latter. A good to very good reproducibility was found for lifestyle factors (smoking: κ = 1.0; exercise: ICC = 0.90), medical factors (drug adherence: ICC = 0.74; sleep apnoea: ICC = 0.87), and psychosocial factors (anxiety and depression: ICC = 0.95; quality of life 12-Item Short-Form Health Survey (SF12): ICC = 0.89), as well as for the majority of de-novo-created variables covering the patient's perceptions, motivation, needs, and preferences. CONCLUSIONS: The present questionnaire demonstrates a highly acceptable reproducibility for all key items and instruments. It thus emerges as a valuable tool for evaluating patient factors associated with coronary risk factor control in CHD patients.

Unfavourable risk factor control after coronary events in routine clinical practice.

BACKGROUND: Risk factor control after a coronary event in a recent European multi-centre study was inadequate. Patient selection from academic centres and low participation rate, however, may underscore failing risk factor control in routine clinical practice. Improved understanding of the patient factors that influence risk factor control is needed to improve secondary preventive strategies. The objective of the present paper was to determine control of the major risk factors in a coronary population from routine clinical practice, and how risk factor control was influenced by the study factors age, gender, number of coronary events, and time since the index event. METHODS: A cross-sectional study determined risk factor control and its association with study factors in 1127 patients (83% participated) aged 18-80 years with acute myocardial infarction and/or revascularization identified from medical records. Study data were collected from a self-report questionnaire, clinical examination, and blood samples after 2-36 months (median 16) follow-up. RESULTS: Twenty-one percent were current smokers at follow-up. Of those smoking at the index event 56% continued smoking. Obesity was found in 34%, and 60% were physically inactive. Although 93% were taking blood-pressure lowering agents and statins, 46% were still hypertensive and 57% had LDL cholesterol >1.8 mmol/L at follow-up. Suboptimal control of diabetes was found in 59%. The patients failed on average to control three of the six major risk factors, and patients with >1 coronary events (p < 0.001) showed the poorest overall control. A linear increase in smoking (p < 0.01) and obesity (p < 0.05) with increasing time since the event was observed. CONCLUSIONS: The majority of coronary patients in a representative Norwegian population did not achieve risk factor control, and the poorest overall control was found in patients with several coronary events. New strategies for secondary prevention are clearly needed to improve risk factor control. Even modest advances will provide major health benefits. TRIAL REGISTRATION: Registered at ClinicalTrials.gov (ID NCT02309255 ).

Patient characteristics and risk factors of participants and non-participants in the NOR-COR study.

OBJECTIVES: We aim to compare patient characteristics and coronary risk factors among participants and non-participants in a survey of CHD patients. METHODS: A cross-sectional study explored characteristics and risk factors in patients hospitalized for acute myocardial infarction and/or revascularization. Study data collected from hospital medical records were compared between participants (n = 1127, 83%) and non-participants (n = 229, 16%), who did not consent to participation in the clinical study. RESULTS: Non-participants showed statistically higher prevalence of women (28% versus 21%), ethnic minorities (6% versus 3%), patients living alone (26% versus 19%), depression (19% versus 6%), anxiety (9% versus 3%), hypertension (54% versus 43%) and diabetes (24% versus 17%). Significantly higher multi-adjusted odds ratios were found for Charlson comorbidity index 3.4 (95% confidence interval (CI), 2.8, 4.3) and depression 14.5 (4.4, 121.5) in non-participants. CONCLUSIONS: Non-participants do have higher prevalence of important coronary risk factors compared to participants, and risk factor control may thus be overestimated in available prevention studies. Patients with somatic comorbidity and depression appear to be at particular risk of non-participation in the present study. New strategies accounting for the causes of nonadherence are important to improve secondary prevention in CHD.

Making robust decisions about the impact of health education programs: Psychometric evaluation of the Health Education Impact Questionnaire (heiQ) in diverse patient groups in Norway.

OBJECTIVE: To undertake a rigorous psychometric evaluation of the widely used eight-scale heiQ version 2.0 (evaluating immediate effects of self-management interventions) in diverse patient groups in Norway. METHODS: Cross-sectional survey data were collected from 1019 Norwegians. Data were extracted from studies among people with musculoskeletal disorders (n=516), psoriasis (n=254), heart disease (n=97), and Type 2 diabetes (n=152). To investigate the factorial validity of the Norwegian heiQ, confirmatory factor analyses (CFA) were carried out using Mplus. RESULTS: One-factor model fit, without modifications, was acceptable for the Emotional distress scale. Only one correlated residual was required to be fitted in each of the other scales to achieve satisfactory model fit. The postulated highly restricted full eight-factor model (no cross-loadings, no correlated residuals) showed good fit to the data. Internal consistency was acceptable for most scales (0.72-0.90) but low for Self-monitoring and insight. CONCLUSION: This study of the Norwegian heiQ replicates the factor structure of the original Australian heiQ, using robust and highly restricted CFA procedures, demonstrating a clean independent clusters model structure. PRACTICE IMPLICATIONS: Researchers, program implementers and policymakers could use the Norwegian heiQ with confidence to generate reliable information on program outcomes and support quality improvement activities.

The role of medical and psychosocial factors for unfavourable coronary risk factor control.

OBJECTIVES: This project aims to identify socio-demographic, medical and psychosocial factors (study factors) associated with coronary risk control and prognosis, and to test their impact in a representative sample of coronary heart disease (CHD) patients. DESIGN: The first phase includes a cross-sectional study designed to explore the association between the study factors and coronary risk factor control in CHD patients. Data from hospital records, a questionnaire, clinical examination and blood samples were collected. The independent effects of study factors on subsequent coronary events will be explored prospectively by controlling for baseline coronary risk factors. In the second phase, we will test the effect of tailored interventions to modify the study factors associated with unfavourable risk profile in phase I. RESULTS: In all 1366 patients (21% women), aged 18-80 years with a coronary event on average 17 (2-38) months prior to study participation were identified (83% participation rate). Of the 239 patients who refused participation, 229 patients consented to analysis of hospital record data (non- participants). CONCLUSIONS: If the study variables contribute to CHD risk factors and prognosis, the present project may be important for the development of prevention programs by tailoring these to the patients perceived needs and behaviour profiles.

Right ventricular systolic pressure response during exercise in adolescents born with atrial or ventricular septal defect.

Our study investigated the abnormal right ventricular systolic pressure response (RVPR) in young patients with isolated atrial septal defect (ASD) or ventricular septal defect (VSD). An abnormal RVPR >50 mm Hg during exercise has been identified as a precursor of pulmonary artery hypertension. The present study included a population-based selection of 44 patients (age 13 to 25 years) with either isolated VSD (n = 27) or ASD (n = 17) and without right ventricular outflow tract obstruction. Of the 44 defects, 28 had been surgically closed (17 ASDs and 11 VSDs); 16 minor VSDs were untreated. Cardiovascular exercise testing and echocardiography at rest and during exercise were performed for all patients and 88 healthy controls. The aerobic capacity was significantly reduced in all patient groups (open VSD, closed VSD, closed ASD). The measurements of right ventricular performance were significantly lower in patients with closed ASD or closed VSD compared to those of the controls and patients with open VSD. Finally, 5% of the controls, no patient with ASD, and 9 patients with VSD (33%), regardless of defect closure, had an abnormal RVPR during exercise. In conclusion, 1/3 of young patients with isolated VSD had an abnormal RVPR during exercise.

Non-invasive measurement of the response of right ventricular pressure to exercise, and its relation to aerobic capacity.

INTRODUCTION: Exercise echocardiography assesses exercise-induced pulmonary hypertension. The upper normal limit of right ventricular systolic pressure during exercise is not well established. Our study aims to investigate the response of right ventricular systolic pressure in relation to aerobic capacity. METHODS AND RESULTS: Cardiopulmonary exercise testing using a treadmill, and echocardiography during supine cycling, were performed in 113 healthy volunteers aged 13 to 25 years. Maximal right ventricular systolic pressure during evaluable exercise studies obtained in 108 subjects showed a Gaussian distribution only after separating the endurance trained subjects, specifically 12 athletes with Z-score of peak oxygen uptake higher than 2.0, from the normally trained group of 97 subjects. Maximal right ventricular systolic pressure during exercise in the normally trained group showed a mean of 38.0 millimetres of mercury, with standard deviation of 7.2, a median value of 39.0, and a range from 17 to 63, and the 95th percentile was 51 millimetres of mercury. In the athletes, the maximal right ventricular systolic pressure was higher, with a median of 55.5, a range from 28 to 69, this being significant, with p equal to 0.004). Of the 12 athletes, 8 (67%) showed a response of right ventricular systolic pressure to exercise exceeding 50 millimetres of mercury, but only 8 of 97 normally trained subjects (8%) showed a similar response, this also being significant, with p less than 0.001. CONCLUSIONS: Our study confirms the great variability in the response of right ventricular systolic pressure to exercise in healthy individuals, with 50 millimetres of mercury representing the upper normal limit. Endurance-trained athletes show higher levels, and two-thirds have abnormal responses exceeding 50 millimetres of mercury.