Low-grade systolic murmurs in healthy middle-aged individuals: innocent or clinically significant? A 35-year follow-up study of 2014 Norwegian men.

OBJECTIVE: To determine whether a low-grade systolic murmur, found at heart auscultation, in middle-aged healthy men influences the long-term risk of aortic valve replacement (AVR) and death from cardiovascular disease (CVD). Setting and subjects. During 1972-1975, 2014 apparently healthy men aged 40-59 years underwent an examination programme including case history, clinical examination, blood tests and a symptom-limited exercise ECG test. Heart auscultation was performed under standardized conditions, and murmurs were graded on a scale from I to VI. No men were found to have grade V/VI murmurs. Participants were followed for up to 35 years. RESULTS: A total of 1541 men had no systolic murmur; 441 had low-grade murmurs (grade I/II) and 32 had moderate-grade murmurs (grade III/IV). Men with low-grade murmurs had a 4.7-fold [95% confidence interval (CI) 2.1-11.1] increased age-adjusted risk of AVR, but no increase in risk of CVD death. Men with moderate-grade murmurs had an 89.3-fold (95% CI 39.2-211.2) age-adjusted risk of AVR and a 1.5-fold (95% CI 0.8-2.5) age-adjusted increased risk of CVD death. CONCLUSIONS: Low-grade systolic murmur was detected at heart auscultation in 21.9% of apparently healthy middle-aged men. Men with low-grade murmur had an increased risk of AVR, but no increase in risk of CVD death. Only 1.6% of men had moderate-grade murmur; these men had a very high risk of AVR and a 1.5-fold albeit non-significant increase in risk of CVD death.

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 enrollment 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.

Changes in autonomic cardiac control in patients with epilepsy after discontinuation of antiepileptic drugs: a randomized controlled withdrawal study.

The aim of this study was to assess cardiac autonomic control in patients with epilepsy before and after withdrawal of antiepileptic drugs (AEDs). The study was prospective, randomized and double blinded. Spectral analysis of heart rate variability (HRV) in 24 h ECG-registration before and after withdrawal of AEDs was used to assess autonomic cardiac control. The assessment of HRV with spectral analysis was based on sinus rhythm and normal heart beats [normal to normal beat (NN)]. Thirty-nine patients had 24 h rhythms free from any ectopic beats both before and after intervention, and were included in the analysis. Significant differences were found in the withdrawal group: filtered RR intervals for all 5 min segments of the analysis; percentage of differences between adjacent filtered RR intervals that are greater than 50 ms for the whole analysis; very low frequency power; low frequency power and high frequency power. The results demonstrate that slow withdrawal of AEDs in seizure-free patients with epilepsy on drug mono-therapy resulted in an increase in both parasympathetic and sympathetic functions, indicative of increased power amongst patients following cessation of AED treatment. As low HRV has been associated with increased mortality in patients with other diseases, this increased HRV may be beneficial.

Response to Intravenous Glucose-Tolerance Test and Risk of Cancer: A Long-Term Prospective Cohort Study.

BACKGROUND: Impaired glucose regulation, measured with an oral glucose-tolerance test, has been associated with the risk of cancer. Here, we explored whether the response to an intravenous glucose-tolerance test (IVGTT) is associated with the risk of cancer. METHODS: A cohort of 945 healthy men, aged 40-59years in 1972-75, was followed for 40years. An IVGTT was performed at baseline. Blood samples for glucose determinations were drawn immediately before glucose injection and thereafter every 10min for 1h. Associations were assessed with incidence rate ratios (IRR) and Cox models. FINDINGS: Cancer incidence was higher among men with 10-min glucose levels below the median than in men with levels above the median (IRR: 1.5, 95% CI: 1.2-1.9). This association remained significant after adjusting for relevant confounders (HR: 1.6, 95% CI: 1.3-2.1) and when excluding the first 10years of follow-up to minimize the possibility of reverse causality (HR: 1.5, 95% CI: 1.2-2.0). INTERPRETATION: Healthy middle-aged males that responded to an intravenous glucose injection with rapid glucose elimination during the first phase had an elevated risk of cancer during 40years of follow-up. First phase response to a glucose load might be related to cancer development.

Restenosis and clinical outcome in patients treated with amlodipine after angioplasty: results from the Coronary AngioPlasty Amlodipine REStenosis Study (CAPARES).

OBJECTIVES: Our intent was to investigate the effect of the dihydropyridine calcium channel blocker amlodipine on restenosis and clinical outcome in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Amlodipine has sustained vasodilatory effects and relieves coronary spasm, which may reduce luminal loss and clinical complications after PTCA. METHODS: In a prospective, double-blind design, 635 patients were randomized to 10 mg of amlodipine or placebo. Pretreatment with the study drug started two weeks before PTCA and continued until four months after PTCA. The primary angiographic end point was loss in minimal lumen diameter (MLD) from post-PTCA to follow-up, as assessed by quantitative coronary angiography (QCA). Clinical end points were death, myocardial infarction, coronary artery bypass graft surgery and repeat PTCA (major adverse clinical events). RESULTS: Angioplasty was performed in 585 patients (92.1%); 91 patients (15.6%) had coronary stents implanted. Follow-up angiography suitable for QCA analysis was done in 236 patients in the amlodipine group and 215 patients in the placebo group (per-protocol group). The mean loss in MLD was 0.30 +/- 0.45 mm in the amlodipine group versus 0.29 +/- 0.49 mm in the placebo group (p = 0.84). The need for repeat PTCA was significantly lower in the amlodipine versus the placebo group (10 [3.1%] vs. 23 patients [7.3%], p = 0.02, relative risk ratio [RR]: 0.45, 95% confidence interval [CI]: 0.22 to 0.91), and the composite incidence of clinical events (30 [9.4%] vs. 46 patients (14.5%), p = 0.049, RR: 0.65, CI: 0.43 to 0.99) within the four months follow-up period (intention-to-treat analysis). CONCLUSIONS: Amlodipine therapy starting two weeks before PTCA did not reduce luminal loss, but the incidence of repeat PTCA and the composite major adverse clinical events were significantly reduced during the four-month follow-up period after PTCA with amlodipine as compared with placebo.

Drug-related deaths in a department of internal medicine.

BACKGROUND: Drug therapy is associated with adverse effects, and fatal adverse drug events (ADEs) have become major hospital problems. Our study assesses the incidence of fatal ADEs in a major medical department and identifies possible patient characteristics signifying fatal ADE risk. METHODS: During a 2-year period, a multidisciplinary study group examined all 732 patients who died--5.2% of the 13992 patients admitted to the Department of Internal Medicine, Central Hospital of Akershus, Nordbyhagen, Norway. Decisions about the presence or absence of fatal ADEs were based on aggregated clinical records, autopsy results, and findings from premortem and postmortem drug analyses. RESULTS: In 18.2% of the patients (133/732) (95% confidence interval, 15.4%-21.0%), deaths were classified as being directly (64 [48.1%] of 133) or indirectly (69 [51.9%] of 133) associated with 1 or more drugs (this equals 9.5 deaths per 1000 hospitalized patients). Those with fatal ADEs (cases) were older, had more diseases, and used more drugs than those without fatal ADEs (noncases). In 75 of the 133 patients with fatal ADEs, autopsy findings and/or drug analysis data were decisive for recognizing the ADEs; in 62 of the remaining 595 patients, similar data proved necessary to exclude the suspicion of a fatal ADE. Major culprit drugs were cardiovascular, antithrombotic, and sympathomimetic agents. CONCLUSIONS: Fatal ADEs represent a major hospital problem, especially in elderly patients with multiple diseases. A higher number of drugs administered was associated with a higher frequency of fatal ADEs, but whether a high number of drugs is an independent risk factor for fatal ADEs is unsettled. Autopsy results and the findings of premortem and postmortem drug analyses were important for recognizing and excluding suspected fatal ADEs.

Type 2 diabetes and maternal family history: an impact beyond slow glucose removal rate and fasting hyperglycemia in low-risk individuals? Results from 22.5 years of follow-up of healthy nondiabetic men.

OBJECTIVE: Although an excess transmission of type 2 diabetes from mothers has been documented, whether this is an independent trait or whether the effect can be detected early through risk factors for type 2 diabetes remains to be elucidated. The objective of this study was to investigate the prevalence of and the possible prospective effect of family history on type 2 diabetes incidence adjusted for multiple diabetes risk factors in a 22.5-year follow-up study of healthy men. RESEARCH DESIGN AND METHODS: A total of 1,947 apparently healthy nondiabetic men with fasting blood glucose (FBG) levels <110 mg/dl at baseline, in whom an intravenous glucose tolerance test (IVGTT) was administered and several conventional risk factors were measured, were followed for 22.5 years. Family history data were obtained at the baseline examination, and morbidity data were obtained from repeated investigations, hospital records, and death certificates. RESULTS: A total of 131 men reported maternal diabetes family history only, 65 men reported paternal diabetes family history only and 10 men reported both maternal and paternal diabetes family history. Among the 1,947 men, 143 cases of type 2 diabetes developed during 22.5 years of observation. Maternal family history and combined maternal and paternal family history predisposed to future type 2 diabetes both in univariate Cox analysis and in multivariate Cox regression analysis after adjusting for glucose disappearance rate (Rd) during an IVGTT, FBG level, BMI, physical fitness, triglyceride level, and age. Maternal family history showed a relative risk (RR) of 2.51 (95% CI 1.55-4.07), combined maternal and paternal family history showed an RR of 3.96 (1.22-12.9), and paternal family history showed an RR of 1.41 (0.657-3.05) in multivariate analysis. CONCLUSIONS: Maternal family history appears to be an important risk factor for type 2 diabetes independent of prediabetic Rd, FBG, BMI, and physical fitness levels.

Fasting blood glucose: an underestimated risk factor for cardiovascular death. Results from a 22-year follow-up of healthy nondiabetic men.

OBJECTIVE: Because of the available conflicting epidemiological data, we investigated the possible impact of fasting blood glucose as a risk factor for cardiovascular death in nondiabetic men. This study reports the results from a 22-year prospective study on fasting blood glucose as a predictor of cardiovascular death. RESEARCH DESIGN AND METHODS: Of the 1,998 apparently healthy nondiabetic men (aged 40-59 years), a total of 1,973 with fasting blood glucose < 110 mg/dl were included in the study in which also a number of conventional risk factors were measured at baseline. RESULTS: After 22 years of follow-up, 483 men had died, 53% from cardiovascular diseases. After dividing men into quartiles of fasting blood glucose level, it was found that men in the highest glucose quartile (fasting blood glucose > 85 mg/dl) had a significantly higher mortality rate from cardiovascular diseases compared with those in the three lowest quartiles. Even after adjusting for age, smoking habits, serum lipids, blood pressure, forced expiratory volume in 1 s, and physical fitness (Cox model), the relative risk of cardiovascular death for men with fasting blood glucose > 85 mg/dl remained 1.4 (95% CI 1.04-1.8). Noncardiovascular deaths were unrelated to fasting blood glucose level. CONCLUSIONS: Fasting blood glucose values in the upper normal range appears to be an important independent predictor of cardiovascular death in nondiabetic apparently healthy middle-aged men.

Exercise blood pressure predicts cardiovascular mortality in middle-aged men.

The outcome of 1999 apparently healthy men aged 40 to 59 years investigated from 1972 through 1975 was ascertained after 16 years to determine whether systolic blood pressure measured with subjects in the sitting position during a bicycle ergometer exercise test adds prognostic information on cardiovascular mortality beyond that of casual blood pressure measured after 5 minutes of supine rest. During a total follow-up of 31,984 patient years, 278 patients died, 150 from cardiovascular causes. Casual blood pressure and pulse pressure as well as peak exercise systolic blood pressure during 6 minutes on the starting workload of 600 kpm/min (approximately 100 W, 5880 J/min) were all related to cardiovascular mortality. The relative risk (RR) of dying from cardiovascular causes associated with an increment of 48.5 mmHg (= 2 SD) in systolic blood pressure at 600 kilopondmeter (kpm)/min was significant (RR = 1.5, 95% confidence interval [CI] = 1.1-2.3, P = .040) even when adjusting for a large number of variables measured in the present study, including age, exercise capacity, smoking habits, and casual blood pressures. The influence of blood pressure at 600 kpm/min was so strong that the predictive value of resting casual blood pressures became nonsignificant when these were analyzed as continuous variables also including exercise blood pressure as a covariate. However, the maximal systolic blood pressure during the exercise test was unrelated to cardiovascular mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise blood pressure predicts mortality from myocardial infarction.

Apparently healthy men (n=1999, 40 to 59 years old) were investigated from 1972 through 1975 to determine whether systolic blood pressure during bicycle ergometer exercise predicts morbidity and mortality from myocardial infarction beyond that of casual blood pressure taken after 5 minutes of supine rest. During a follow-up of 31 984 patient-years (average, 16 years), 235 subjects had myocardial infarctions, of which 143 were nonfatal and 92 were fatal. Exercise blood pressure was more strongly related than casual blood pressure to both morbidity and mortality from myocardial infarction. Among 520 men with casual systolic blood pressure = 140 mm Hg, 304 increased their systolic blood pressure to > or = 200 mm Hg during 6 minutes of exercise at an initial workload of 600 kpm/min. These 304 men had an excessive risk of myocardial infarction (18.8% versus 9.5% among the 1294 men with casual blood pressure < 140 mm Hg and exercise blood pressure < 200 mm Hg; P < .001). As many as 58% of those with myocardial infarction in this group died, compared with 33% (range, 26% to 35%) for all other groups (P=.0011), including those with casual blood pressure > or = 140 mm Hg and exercise blood pressure < 200 mm Hg. Thus, exercise blood pressure is a stronger predictor than casual blood pressure of morbidity and mortality from myocardial infarction, and an early rise in systolic blood pressure during exercise adds prognostic information about mortality from myocardial infarction among otherwise healthy middle-aged men with mildly elevated casual blood pressure. We suggest that blood pressure taken during standardized exercise testing may distinguish between severe and less severe hypertension.

Predictors of 7-year changes in exercise blood pressure: effects of smoking, physical fitness and pulmonary function.

BACKGROUND: The health status of 1999 apparently healthy men, aged 40-59 years, was ascertained after 16 years. We found that their systolic blood pressure during an ergometer exercise test added prognostic information beyond that from their blood pressure at rest concerning total cardiovascular mortality and mortality from myocardial infarction. OBJECTIVE: To determine predictors of the change in systolic blood pressure at rest during 7 years and of the change in the prognostically important peak exercise systolic blood pressure at 600 kilopondmetres/min during 7 years. METHODS: Predictors of the changes in blood pressures were investigated in 1393 middle-aged men who had been healthy without drug treatment for chronic disease or hypertension for 7 years. Twelve potential independent predictors were investigated. RESULTS: Previous blood pressures, age and body mass index were independent predictors and could explain 18% of the change in systolic blood pressure at rest over 7 years. For systolic blood pressure at 600 kilopondmetres/min also smoking was associated with a rise whereas a high body mass index, physical fitness and forced expiratory volume in 1 s (all P< 0.001) were associated with lower blood pressure, explaining 19% of the variability. CONCLUSIONS: Beyond a relatively strong tracking of blood pressures and the expected effect of age, smoking is associated with a 7-year rise in exercise systolic blood pressure whereas relatively higher body mass, physical fitness and pulmonary function are associated with lower exercise systolic blood pressure after 7 years in middle-aged healthy men.

Clustering of coronary risk factors with increasing blood pressure at rest and during exercise.

BACKGROUND: The metabolic cardiovascular syndrome is the label given to the clustering of unfavourable levels of a number of coronary risk factors in subjects with high resting blood pressures. We found recently that exercise blood pressure had a strong independent prognostic value. OBJECTIVE: To search for possible similar associations between exercise blood pressure levels and coronary risk factors by studying conventional and recently acknowledged coronary risk factors. METHODS: The study population comprised 1999 healthy men aged 40-59 years. Age-adjusted coronary risk factor levels and their relation to resting and exercise blood pressures were studied. Resting blood pressure was measured after subjects had rested supine for 5 min. The exercise blood pressure used was the systolic blood pressure measured with the subject sitting on a bicycle ergometer at the end of a work load of 600 kpm/min (100 W) for 6 min. RESULTS: Besides corroborating the relation between the metabolic syndrome and resting blood pressure levels, we observed similar or even stronger associations between levels of various coronary risk factors and exercise blood pressure. We found rather strong, direct associations between exercise blood pressure and total cholesterol level, fasting triglyceride level and body mass index whereas inverse relations were found for glucose tolerance, physical fitness, pulmonary functioning and the ability to increase heart rate during exercise. Virtually all these associations had a level of statistical significance of P<0.001. CONCLUSIONS: High exercise blood pressure levels are strongly associated with unfavourable levels of a number of important coronary risk factors. A similar metabolic syndrome to that observed in subjects with high resting blood pressures therefore appears to be present in subjects with high exercise blood pressure responses. These associations may considerably amplify the independent risk of high blood pressure responses to moderate exercise.

Supine and exercise systolic blood pressure predict cardiovascular death in middle-aged men.

AIM AND METHODS: The outcome of 1999 apparently healthy men, aged 40-59 years, initially investigated in the period 1972-1975, has previously been ascertained at 7 and 16 year follow-ups. This has now been repeated after 21 years, to determine whether seated systolic blood pressure (BP) during a bicycle ergometer exercise test adds prognostic information on cardiovascular (CV) mortality beyond that of systolic BP measured after 5 min of supine rest. RESULTS: After 21 years, 41 979 years of observation, 470 patients had died, 255 from CV causes. Supine systolic BP [2 SD increase: relative risk (RR) 1.6, 95% confidence interval (CI) 1.3-2.0, P < 0.0001], 6 min exercise systolic BP (2 SD increase: RR 1.6, 95% CI 1.3-2.0, P < 0.0001) on the starting workload of 600 kpm/min (approximately 100 W, 5880 J/min) and maximal systolic BP (2 SD increase: RR 1.5, 95% CI 1.2-1.9, P = 0.0005) during work were all related to CV mortality when adjusting for a large number of variables measured in the present study including age, exercise capacity, heart rates, smoking habits, glucose tolerance and serum cholesterol. When including other systolic BPs in the continuous multivariate analysis, supine systolic BP (2 SD increase: RR 1.4, 95% CI 1.04-1.9, P = 0.029) and 6 min systolic BP at 600 kpm/min (2 SD increase: RR 1.4, 95% CI 1.06-1.9, P = 0.017) were independent predictors of CV death but not maximal systolic BP during exercise (2 SD increase: RR 1.0, 95% CI 0.7-1.2, P = 0.95). CONCLUSION: These results are different from the mortality data at 16 years, when the independent predictive effect of supine systolic BP was cancelled out by 6 min exercise systolic BP at 600 kpm/min. Twenty-one years of follow-up of 1999 apparently healthy men disclose independently predictive information on CV death, of both supine systolic BP and 6 min exercise systolic BP taken at an early moderate workload. The influence of maximal exercise systolic BP on CV death is however cancelled out by the two other systolic BPs.

Chronic effect of smoking on platelet count and "platelet adhesiveness" in presumably healthy middle-aged men.

In 386 men aged 40-49 years the number of platelets was related to differences in smoking habits. "Platelet adhesiveness" (retention) was estimated by a glass bead filter method in 376 of these men. The estimation of "adhesiveness" was performed in native blood without anticoagulants at least 12 hr after the last cigarette smoked. A small but statistically highly significant increase in platelet count, in number of "adhesive platelets" and percentage of "adhesive platelets" was found in smokers as compared with non-smokers, the highest values being found in the heaviest smokers and vice versa. Such smoking-related changes in platelet count and reactiveness might unfavourably influence the tendency towards coronary thrombosis, and might in part explain the deleterious effects of smoking on coronary heart disease morbidity and mortality.

ABO blood groups and coronary heart disease (CHD). A study in subjects with severe and latent CHD.

The view based on epidemiological and laboratory data that blood group A subjects (=A) have clinically significant higher thrombotic potential than blood group 0 subjects (=O), is supported by the present finding of a significantly higher platelet retention in A than 0. The completely normal AB0 distribution found among 71 cases of proven latent CHD, and the disproportionate excess of 0 vs. A in a consecutive series of 191 coronary artery bypass candidates apparently conflict with epidemiological data indicating a higher risk of achieving CHD in A than 0. The conflict may be solved by suggesting a) that the "thrombotic proneness" in A compared with 0 causes a poorer prognosis in CHD among the former, leaving a disproportionate excess of 0 among longterm CHD survivors, and b) that AB0-related factors have had an insignificant, independent impact on the evolution of preclinical coronary artery disease in our 71 men with latent CHD.

Initial clinical presentation of cardiac disease in asymptomatic men with silent myocardial ischemia and angiographically documented coronary artery disease (the Oslo Ischemia Study).

Data concerning the natural history of asymptomatic coronary artery disease (CAD) has been limited to epidemiologic rather than angiographic studies, thus leading to uncertainty as to whether warning symptoms and signs will identify subjects with silent myocardial ischemia before morbid events. To address this issue, 50 apparently healthy men with angiographically proven CAD and asymptomatic exercise-induced ST depression have been followed prospectively for 15 years in the Oslo Ischemia Study. Fourteen men died. The initial presenting clinical event in these 14 men was chest pain in 4 (30%)--but in only 1 case was it recognized as typical angina--silent myocardial infarction in 5 (35%) and sudden death in 5 (35%). Thirty-six men survived, with 19 developing symptoms. Overall, chest pain was the first clinical event in 22 of the total of 33 men with symptoms (66%), whereas myocardial infarction occurred in 6 (18%) and sudden death in 5 (16%). Although chest pain occurred in 22 men, it was clinically diagnosed as typical angina pectoris in only 6. These observations suggest that there is an absence of clear-cut ischemic symptoms in many asymptomatic patients before morbid events.

Health status, dyspnea, lung function and exercise capacity in patients with chronic obstructive pulmonary disease.

SETTING: A secondary hospital outside Oslo. OBJECTIVE: To assess relationships between health status and measures of dyspnea, lung function and exercise capacity in patients with chronic obstructive pulmonary disease (COPD), to identify dimensions where lung-specific instruments associate and discriminate better than general measures. DESIGN: We assessed health status in 59 out-patients with COPD, using the following instruments: Short Form 36 (SF-36)-a general health status measure, Respiratory Quality of Life Questionnaire (RQLQ)-a lung-specific measure, the Karnofsky performance scale, and a rating scale. All patients rated their dyspnea and had spirometry and exercise capacity measured. RESULTS: Mean (SD) patient age was 57.3 (9.7) years, FEV1 47% (15%) of predicted, 6 minute walk distance 503 m (122 m). Dyspnea was the strongest predictor for health status. Both SF-36 and RQLQ had dimensions associating well with dyspnea and exercise capacity. The associations with FEV1 ranged from none to moderate. CONCLUSION: All RQLQ scales had a moderate to substantial association with indices of dyspnea and exercise capacity, while the SF-36 associated well only in dimensions related to physical health. The general measure has a broader scope and complements the lung-specific measure. These findings support the construct validity of both the SF-36 and the RQLQ, and justify using a general measure to supplement a lung-specific measure.

Heart rate increase and maximal heart rate during exercise as predictors of cardiovascular mortality: a 16-year follow-up study of 1960 healthy men.

BACKGROUND: Resting heart rate is directly associated and maximal exercise-induced heart rate inversely associated with cardiovascular mortality, and therefore their difference might contain prognostic information from both variables. The comparative long-term prognostic values of maximal exercise-induced heart rate and of the difference between it and resting heart rate were studied in apparently healthy middle-aged men. METHODS: Resting heart rate and maximal exercise-induced heart rate were measured, and their difference calculated, in 1960 apparently healthy men aged 40-59 years, and mortality was recorded over a period of 16 years. Conventional coronary risk factors were assessed at baseline. RESULTS: Both the difference between the two heart rates and the maximal exercise-induced heart rate were strongly, independently and inversely associated with cardiovascular mortality after adjustment for age, smoking, systolic blood pressure, lung function, glucose tolerance, serum cholesterol level, serum triglycerides level, physical fitness and exercise ECG findings. The adjusted relative risk of cardiovascular death in heart-rate difference quartiles 3 and 4 compared with that in quartile 1 (the lowest heart-rate difference quartile) was 0.54 (95% confidence interval 0.33-0.86; P = 0.009). The corresponding value for maximal exercise-induced heart rate was 0.56 (95% confidence interval 0.34-0.89; P = 0.018). Within the lowest heart-rate difference quartile, but not within the lowest maximal exercise-induced heart rate quartile, a further, strong, negative gradient in cardiovascular mortality was observed. In the high working capacity range, low heart-rate difference but not low maximal exercise-induced heart rate predicted very high cardiovascular disease mortality. Heart-rate difference and maximal exercise-induced heart rate were also inversely associated with non-cardiovascular disease mortality. CONCLUSIONS: Both heart-rate difference and maximal exercise-induced heart rate were strong, graded, long-term predictors of cardiovascular mortality among apparently healthy middle-aged men, independent of age, physical fitness and conventional coronary risk factors. However, low heart-rate difference was a better predictor than low maximal exercise-induced heart rate for recognizing individuals who were at particularly high risk of dying prematurely from cardiovascular diseases.

Health-related quality of life is associated with arterial P(O2) in chronic obstructive pulmonary disease.

Insensitive lung-specific questionnaires may explain the poor association between arterial P(O2) and reported health-related quality of life. Conceivably, modern lung specific or generic quality of life measures might show a better association with arterial P(O2). Fifty-nine outpatients (34 men) with chronic obstructive pulmonary disease (COPD) who fulfilled the following criteria were studied: age 18-67 years, FEV1 < or = 70%, < or = 15% reversibility after beta2-agonist inhalation, and no other disabling disorders. All completed the Respiratory Quality of Life Questionnaire (RQLQ) and Short Form 36 (SF-36), and were tested with spirometry and arterial blood gases. In accordance with available COPD staging systems, patients were divided into those with an FEV1 of < 50% and 50-70% of predicted. Patients' characteristics were, [mean (SD)]: age: 57.0 years (9.0); FEV1: 1.46 (0.6). Spearman's rank correlations between arterial P(O2) and dimensions of the RQLQ ranged from 0.25-0.52, and were greater than for the SF-36 (0.14-0.36) in patients with moderate to severe COPD. The association between arterial P(O2) and quality of life scores in moderately to severely affected COPD patients was moderate, but higher than previously reported. The associations were higher with a lung-specific questionnaire than with a general health measure, indicating a higher sensitivity of the lung-specific measure in this patient group.

Performance of a short lung-specific health status measure in outpatients with chronic obstructive pulmonary disease.

The objective of this study was to assess the performance of a lung-specific health status measure in patients with chronic obstructive pulmonary disease (COPD). We used the Respiratory Quality of Life Questionnaire (RQLQ), a modification of an Australian questionnaire intended for asthma patients and adapted in this study to fit patients with COPD also. For comparison we chose the general health profile measure Short Form 36 (SF-36). We assessed the five RQLQ scales and eight SF-36 scales for reliability, validity and responsiveness in 59 outpatients attending a Norwegian hospital for COPD. Statistical analysis included internal consistency, test-retest reliability and convergent validity between the two questionnaires. Responsiveness was assessed in patients reporting global change in health status over 1 year. All scales of the RQLQ showed good internal consistency (Cronbach's a = 0.85-0.94) and test-retest reliability (intraclass correlation coefficient = 0.86-0.94), as did the SF-36 scales (a = 0.66-0.90) and intraclass correlation coefficient = 0.60-0.86). Pearson correlations between scales with similar items ranged from 0.54 to 0.76, supporting the construct validity of both questionnaires. The RQLQ had responsive scales, showing significant changes in the expected direction over 1 year. We conclude that the RQLQ showed an acceptable reliability, construct validity and responsiveness in COPD patients, encouraging further use of this questionnaire.