Jørgen Fischer Hansen

High serum YKL-40 concentration is associated with cardiovascular and all-cause mortality in patients with stable coronary artery disease

AIMS Macrophages in atherosclerotic plaques secrete YKL-40. We tested the hypothesis if high serum YKL-40 concentration predicts coronary events and death of patients with stable coronary artery disease (CAD). METHODS AND RESULTS During the 2.6 years follow-up period (median 2.77 year, interquartile range 0.23 year), 270 patients among the 4298 patients with stable CAD in the CLARICOR trial suffered myocardial infarction (MI) and 377 died (187 classified as cardiovascular death). Serum YKL-40 transformed as Y=log[max(82, serum YKL-40/microg/L)] was significantly associated with cardiovascular death [hazard ratio (HR) = 1.88, 95% confidence interval (CI) = 1.54-2.31, P < 0.001], all-cause mortality (HR = 2.01, 95% CI = 1.75-2.31, P < 0.001), and MI (HR = 1.38, 95% CI = 1.13-1.68, P = 0.002). Following multivariable adjustment for cardiovascular risk factors (age, sex, previous MI, smoking status, hypertension, diabetes mellitus) and selected medical treatments Y contributed significantly to prediction of all-cause mortality (P < 0.001) and cardiovascular mortality (P = 0.001), but not MI (P = 0.25). CONCLUSION High serum YKL-40 is associated with MI, cardiovascular and all-cause mortality in patients with stable CAD.

Risk assessment of left ventricular systolic dysfunction in primary care : cross sectional study evaluating a range of diagnostic tests

Abstract Objectives: To assess the probability of left ventricular systolic dysfunction without echocardiography in patients from general practice. Design: Cross sectional study using multivariate regression models to examine the relation between clinical variables and left ventricular systolic dysfunction as determined by echocardiography. Setting: Three general practices in Copenhagen. Subjects: 2158 patients aged >40 years were screened by questionnaires and case record reviews; 357 patients with past or present signs or symptoms of heart disease were identified, of whom 126 were eligible for and consented to examination. Main outcome measures: Clinical variables that were significantly (P<0.05) related to ejection fraction 0.45 and their predictive value for left ventricular systolic dysfunction. Results: 15 patients (12%) had left ventricular systolic dysfunction. The prevalence was significantly related to three questions: does the electrocardiogram have Q waves, left bundle branch block, or ST-T segment changes? (P=0.012); is resting supine heart rate greater than the simultaneous diastolic blood pressure? (P=0.002); and is plasma N-terminal atrial natriuretic peptide>0.8 nmol/l? (P=0.040)? Only one of 60 patients with a normal electrocardiogram had systolic dysfunction (2%, 95% confidence interval 0% to 9%) regardless of response to the other two questions. The risk of dysfunction was appreciable in patients with a yes answer to two or three questions (50%, 27% to 73%). Conclusions: A normal electrocardiogram implies a low risk of left ventricular systolic dysfunction. Patients can be identified for echocardiography on the basis of an abnormal electrocardiogram combined with increased natriuretic peptide concentration or a heart rate greater than diastolic blood pressure, or both. Key messages Early treatment of left ventricular systolic dysfunction reduces morbidity, but diagnosis relies on echocardiography This study examines methods for assessing the risk of left ventricular systolic dysfunction in patients from primary care with past or present signs or symptoms of heart disease Risk can be assessed by three factors: QRS or ST-T changes in the electrocardiogram; increased plasma concentration of N-terminal atrial natriuretic peptide; and tachycardia (supine resting heart rate>diastolic blood pressure) Risk of systolic dysfunction was very low in patients with normal electrocardiographic results Risk was high in patients who had an abnormal electrocardiogram in combination with at least one other abnormal result

Enhanced sympathetic nervous activity after intravenous propranolol in ischaemic heart disease: plasma noradrenaline splanchnic blood flow and mixed venous oxygen saturation at rest and during exercise

Abstract. To study the mechanisms by which acute beta‐adrenergic blockade may change the activity of the sympathetic nervous system we have measured haemody‐namic responses including splanchnic blood flow in twenty‐three patients with ischaemic heart disease at rest and during supine exercise before and after i.v. injection of 0.039 mmol (10 mg) dl‐propranolol.

Cross sectional study estimating prevalence of heart failure and left ventricular systolic dysfunction in community patients at risk

OBJECTIVE To examine a general practice population to measure the prevalence of signs and symptoms of heart failure (SSHF) and left ventricular systolic dysfunction (LVSD). DESIGN Cross sectional screening study in three general practices followed by echocardiography. SETTING AND PATIENTS All patients ⩾ 50 years in two general practices and ⩾ 40 years in one general practice were screened by case record reviews and questionnaires (n = 2158), to identify subjects with some evidence of heart disease. Among these, subjects were sought who had SSHF (n = 115). Of 357 subjects with evidence of heart disease, 252 were eligible for examination, and 126 underwent further cardiological assessment, including 43 with SSHF. MAIN OUTCOME MEASURES Prevalence of SSHF as defined by a modified Boston index, LVSD defined as an indirectly measured left ventricular ejection fraction ⩽ 0.45, and numbers of subjects needing an echocardiogram to detect one case with LVSD. RESULTS SSHF afflicted 0.5% of quadragenarians and rose to 11.7% of octogenarians. Two thirds were handled in primary care only. At ⩾ 50 years of age 6.4% had SSHF, 2.9% had LVSD, and 1.9% (95% confidence interval 1.3% to 2.5%) had both. To detect one case with LVSD in primary care, 14 patients with evidence of heart disease without SSHF and 5.5 patients with SSHF had to be examined. CONCLUSION SSHF is extremely prevalent in the community, especially in primary care, but more than two thirds do not have LVSD. The number of subjects with some evidence of heart disease needing an echocardiogram to detect one case of LVSD is 14.

Sex related differences in short and long-term prognosis after acute myocardial infarction: 10 year follow up of 3073 patients in database of first Danish Verapamil Infarction Trial.

Abstract Objective: To re-examine the prevailing hypothesis that women fare worse than men after acute myocardial infarction. Design: 10 year follow up of all patients with confirmed acute myocardial infarction registered in the database of the Danish verapamil infarction trial in 1979-81. Setting: 16 coronary care units, covering a fifth of the total Danish population. Patients: 3073 consecutive patients with acute myocardial infarction, 738 (24%) women and 2335 (76%) men. Main outcome measures: Early mortality (before day 15). For patients alive on day 15: mortality, cause of death, admission with recurrent infarction, and mortality after reinfarction. Results: Early mortality increased significantly with age (P<0.0001) but was not significantly related to sex, with a 15 day mortality of 17% in women and 16% in men. Adjustment for age and sex simultaneously revealed a significant interaction (P=0.02) between these variables, with a greater increase with age in early mortality for men than for women (early mortality was equal for the two sexes at age 64 years). Ten year mortality in patients alive on day 15 was 58.8%. The overall age adjusted hazard ratio (95% confidence interval) for women versus men was 0.90 (0.80 to 1.01); 0.90 (0.78 to 1.04) for 10 year reinfarction (48.8%); and 0.98 (0.82 to 1.16) for 10 year mortality after reinfarction (82.3%). No difference in cause of death was found between the sexes. With a follow up of up to 10 years for patients alive on day 15 mortality, rate of reinfarction, and mortality after reinfarction increased with increasing age (P<0.0001). Conclusion: Sex by itself is not a risk factor after acute myocardial infarction. Key messages Women and men have similar mortality at 10 year follow up Causes of death are not different between the sexes Women and men have similar reinfarction rates and similar subsequent mortality The prevailing view regarding sex as an independent prognostic factor after acute myocar- dial infarction may be due to present differences in treatment of women and men, selection bias, and the interpretation of the role of age differences

Clarithromycin for 2 Weeks for Stable Coronary Heart Disease: 6-Year Follow-Up of the CLARICOR Randomized Trial and Updated Meta-Analysis of Antibiotics for Coronary Heart Disease

Objectives: We have reported increased 2.6-year mortality in clarithromycin- versus placebo-exposed stable coronary heart disease patients, but meta-analysis of randomized trials in coronary heart disease patients showed no significant effect of antibiotics on mortality. Here we report the 6-year mortality of clarithromycin- versus placebo-exposed patients and updated meta-analyses. Methods: Centrally randomized, placebo controlled multicenter trial. All parties were blinded. Analyses were by intention to treat. Meta-analyses followed the Cochrane Collaboration methodology. Results: We randomized 4,372 patients with stable coronary heart disease to clarithromycin 500 mg (n = 2,172) or placebo (n = 2,200) once daily for 2 weeks. Mortality was followed through public register. Nine hundred and twenty-three patients (21.1%) died. Six-year mortality was significantly higher in the clarithromycin group (hazard ratio 1.21, 95% confidence interval 1.06–1.38). Adjustment for entry characteristics (sex, age, prior myocardial infarction, center, and smoking) did not change the results (1.18, 1.04–1.35). Addition of our data to that of other randomized trials on antibiotics for patients with coronary heart disease versus placebo/no intervention (17 trials, 25,271 patients, 1,877 deaths) showed a significantly increased relative risk of death from antibiotics of 1.10 (1.01–1.20) without heterogeneity. Conclusions: Our results stress the necessity to consider carefully the strength of the indication before administering antibiotics to patients with coronary heart disease.

Home-based cardiac rehabilitation is an attractive alternative to no cardiac rehabilitation for elderly patients with coronary heart disease: results from a randomised clinical trial

Objective To compare home-based cardiac rehabilitation (CR) with usual care (control group with no rehabilitation) in elderly patients who declined participation in centre-based CR. Design Randomised clinical trial with 12 months follow-up and mortality data after 5.5 years (mean follow-up 4½ years). Setting Rehabilitation unit, Department of Cardiology, Copenhagen, Denmark. Participants Elderly patients ≥65 years with coronary heart disease. Intervention A physiotherapist made home visits in order to develop an individualised exercise programme that could be performed at home and surrounding outdoor area. Risk factor intervention, medical adjustment, physical and psychological assessments were offered at baseline and after 3, 6 and 12 months. Main outcome measurements The primary outcome was 6 min walk test (6MWT). Secondary outcomes were blood pressure, body composition, cholesterol profile, cessation of smoking, health-related quality of life (HRQoL), anxiety and depression. Results 40 patients participated. The study population was characterised by high age (median age 77 years, range 65–92 years) and high level of comorbidity. Patients receiving home-based CR had a significant increase in the primary outcome 6MWT of 33.5 m (95% CI: 6.2 to 60.8, p=0.02) at 3 months, whereas the usual care group did not significantly improve, but with no significant differences between the groups. At 12 months follow-up, there was a decline in 6MWT in both groups; −55.2 m (95% CI: 18.7 to 91.7, p<0.01) in the home group and −52.1 m (95% CI: −3.0 to 107.1, p=0.06) in the usual care group. There were no significant differences in blood pressure, body composition, cholesterol profile, cessation of smoking or HRQoL after 3, 6 and 12 months follow-up. Conclusions Participation in home-based CR improved exercise capacity among elderly patients with coronary heart disease, but there was no significant difference between the home intervention and the control group. In addition, no significant difference was found in the secondary outcomes. When intervention ceased, the initial increase in exercise capacity was rapidly lost.

C-reactive protein, heart rate variability and prognosis in community subjects with no apparent heart disease

Objectives.  Increased C‐reactive protein (CRP) and reduced heart rate variability (HRV) both indicate poor prognosis. An inverse association between HRV and CRP has been reported, suggesting an interaction between inflammatory and autonomic systems. However, the prognostic impact of this interaction has not been studied. We thus investigated the prognostic impact of CRP, HRV and their combinations.

Long-term effects of diltiazem and verapamil on mortality and cardiac events in non–Q-wave acute myocardial infarction without pulmonary congestion: post hoc subset analysis of the multicenter diltiazem postinfarction trial and the second danish verapamil infarction trial studies ☆

The main objective of this retrospective analysis was to evaluate the long-term effect of the heart rate-lowering calcium antagonists verapamil and diltiazem on the incidence of combined cardiac events and all-cause mortality in patients who had experienced a non-Q-wave acute myocardial infarction (AMI), but who did not also have pulmonary congestion. In addition, factors having an independent association with these 2 outcomes were identified. Of 817 non-Q-wave patients, 81 (9.9%) died during 12 to 52 months of follow-up. The unadjusted mortality rate was 42% lower in patients randomized to calcium antagonist therapy than placebo (7.2% vs 12.4%, p = 0.010). Non-Q-wave patients who died during follow-up were older than patients who survived (62 vs 58 years, p = 0.001). Other factors found to have an independent association with all-cause mortality included diuretic use (RR 2.79), diabetes mellitus (RR 2.86), and New York Heart Association class >I (RR 1.73). The covariate adjusted all-cause mortality risk ratio associated with randomization to calcium antagonist therapy was 0.65 (95% confidence interval [0.40 to 1.05, p = 0.079]). Overall, 153 patients (18.7%) died or had nonfatal reinfarction. The unadjusted combined event rate was 31% lower in patients randomized to calcium antagonist therapy than to placebo (15.2% vs 21.9%, p <0.006). Factors found to have an independent association with cardiac events included age, diabetes (RR 2.82), diuretic use (RR 2.04), and previous AMI (RR 1. 71). In addition, randomization to the calcium antagonist group had a significant independent association with reduced cardiac events (p = 0.031). The covariate adjusted event rate RR associated with randomization to the calcium antagonist group was 0.69 (95% confidence interval [0.49 to 0.97]). In conclusion, the heart rate-lowering calcium antagonists diltiazem and verapamil may play an important role in reducing long-term mortality and reinfarction in non-Q-wave AMI without pulmonary congestion.

Predictors of sudden death and death from pump failure in congestive heart failure are different. Analysis of 24 h Holter monitoring, clinical variables, blood chemistry, exercise test and radionuclide angiography

One hundred and ninety consecutive patients discharged with congestive heart failure were examined with clinical evaluation, blood chemistry, 24 h Holter monitoring, exercise test and radionuclide angiography. Median left ventricular ejection fraction was 0.30, 46% were in New York Heart Association class II and 44% in III. Total mortality after 1 year was 21%, after 2 years 32%. Of 60 deaths, 33% were sudden and 49% due to pump failure. Multivariate analyses identified totally different risk factors for sudden death: ventricular tachycardia, s-sodium < or = 137 mmol/l, s-magnesium < or = 0.80 mmol/l, s-creatinine > 121 mumol/l, and maximal change in heart rate during exercise < or = 35 min-1, and for death from progressive pump failure: New York Heart Association class III + IV, delta heart rate over 24 h < or = 50 min-1, low ejection fraction, high resting p-noradrenaline, s-urea > 7.6 mmol/l, s-potassium < 3.5 mmol/l, and maximal exercise duration < or = 4 min. In conclusion, this study demonstrated different risk factors for sudden death and for death from progressive pump failure.