Heli Koukkunen

C-reactive protein, fibrinogen, interleukin-6 and tumour necrosis factor-α in the prognostic classification of unstable angina pectoris

BACKGROUND. Inflammatory process has been found to play an important role in the pathogenesis of coronary heart disease (CHD) and in the prognosis of CHD patients. AIM. The aim of this study was to investigate the prognostic value of C-reactive protein (CRP), fibrinogen, interleukin (IL)-6 and tumour necrosis factor-α (TNF-α) in patients with unstable angina pectoris (UAP), including factor analysis to assess their joint effects. METHODS. The study comprised 263 consecutive patients (159 men, 104 women; median age 68 years) with UAP. Blood samples for the acute-phase protein and cytokine determinations were drawn on admission. RESULTS. Coronary mortality during the median follow-up time of 17 months was 6-fold higher in the highest tertile for CRP and IL-6 and 3.5-fold higher in the highest tertile for fibrinogen and TNF-α than in the respective combined lower tertiles. Factor analysis produced two underlying factors, ie the ‘inflammation’ factor, including CRP, fibrinogen and IL-6, and the ‘injury’ factor, including troponin T, creatine kinase MB mass and TNF-α. In Cox models, both of these factors were independent predictors of the risk of coronary death and major coronary events (coronary death or nonfatal myocardial infarction). CONCLUSIONS. Elevated levels of acute-phase proteins and cytokines, particularly CRP and IL-6, are strong predictors of the risk of serious coronary events in patients with UAP.

Trends in coronary events in Finland during 1983–1997; The FINAMI study

AIMS To analyse the trends in incidence, recurrence, case fatality, and treatments of acute coronary events in Finland during the 15-year period 1983-97. METHODS AND RESULTS Population-based MI registration has been carried out in defined geographical areas, first as a part of the FINMONICA Project and then continued as the FINAMI register. During the study period, 6501 coronary heart disease (CHD) events were recorded among men and 1778 among women aged 35-64 years. The CHD mortality declined on average 6.4%/year (95% confidence interval -5.4, -7.4%) among men and 7.0%/year (-4.7, -9.3%) among women. The mortality from recurrent events declined even more steeply, 9.9%/year (-8.3, -11.4%) among men and 9.3%/year (-5.1, -13.4%) among women. The proportion of recurrent events of all CHD events also declined significantly in both sexes. Of all coronary deaths, 74% among men and 61% among women took place out-of-hospital. The decline in 28-day case fatality was 1.3%/year (-0.3, -2.3%) among men and 3.1%/year (-0.7, -5.5%) among women. CONCLUSIONS The study period was characterized by a marked reduction in the occurrence of recurrent CHD events and a relatively modest reduction in the 28-day case fatality. The findings suggest that primary and secondary prevention have played the main roles in the decline in CHD mortality in Finland.

Differences in the diagnosis of myocardial infarction by troponin T compared with clinical and epidemiologic criteria

We investigated the difference in the number of myocardial infarction (MI) diagnoses based on troponin T compared with clinical and epidemiologic (modified FINnish Multinational MONItoring of trends and determinants in CArdiovascular diseases) diagnoses, and the prognosis of patients with discordant diagnoses. Five hundred fifty-nine consecutive patients (315 men and 244 women, median age 69 years) were admitted to the hospital with a suspected acute coronary syndrome. Median follow-up time was 17 months. Of the 559 patients, 127 had a clinical and 137 an epidemiologic diagnosis of MI. When a diagnosis of MI was primarily based on troponin T (>0.10 microg/L), the number of MIs was 169, which increased by 33% compared with the number of MIs by clinical diagnosis, and by 23% compared with those by epidemiologic diagnosis. However, troponin T was not elevated in 13% of the 127 patients with the clinical diagnosis and in 14% of the 137 patients with the epidemiologic diagnosis of MI. Among patients in whom clinical diagnosis of MI was not made, the prognosis with regard to coronary death or nonfatal MI was not significantly worse in patients with troponin T >0.10 microg/L than < or =0.10 microg/L (hazard ratio 1.07; 95% confidence interval 0.62 to 1.84). In patients with a suspected acute coronary syndrome, troponin T-based diagnostics leads to an increase in the number of patients diagnosed with MI compared with clinical or epidemiologic diagnosis. The prognostic impact of troponin T in patients without clinical diagnosis of MI based on elevations in conventional enzyme activities needs further study in larger series of patients.

Decline in Out-of-Hospital Coronary Heart Disease Deaths Has Contributed the Main Part to the Overall Decline in Coronary Heart Disease Mortality Rates Among Persons 35 to 64 Years of Age in Finland The FINAMI Study

Background—Out-of-hospital deaths constitute the majority of all coronary heart disease (CHD) deaths and are therefore of considerable public health significance. Methods and Results—We used population-based myocardial infarction register data to examine trends in out-of-hospital CHD deaths in Finland during 1983 to 1997. We included in out-of-hospital deaths also deaths in the emergency room and all deaths within 1 hour after the onset of symptoms. Altogether, 3494 such events were included in the analyses. The proportion of out-of-hospital deaths of all CHD deaths depended on age and gender. In the age group 35 to 64 years, it was 73% among men and 60% among women. These proportions did not change during the study. The annual average decline in the age-standardized out-of-hospital CHD death rate was 6.1% (95% CI, −7.3, −5.0%) among men and 7.0% (−10.0, −4.0%) among women. These declines contributed among men 70% and among women 58% to the overall decline in CHD mortality rate. In all, 58% of the male and 52% of the female victims of out-of-hospital CHD death had a history of symptomatic CHD. Among men with a prior history of myocardial infarction, the annual average decline in out-of-hospital CHD deaths was 5.3% (−7.2, −3.2%), and among men without such history the decline was 2.9% (−4.4, −1.5%). Among women, the corresponding changes were −7.8% (−14.2, −1.5%) and −4.5% (−8.0, −1.0%). Conclusions—The decline in out-of-hospital CHD deaths has contributed the main part to the overall decline in CHD mortality rates among persons 35 to 64 years of age in Finland.

Myoglobin, creatine kinase MB isoforms and creatine kinase MB mass in early diagnosis of myocardial infarction in patients with acute chest pain.

OBJECTIVES Measurements of myoglobin and creatine kinase (CK)-MB isoforms have been suggested to be sensitive tests for the early diagnosis of myocardial infarction (MI). We have investigated the utility of myoglobin, creatine kinase (CK)-MB isoforms and creatine kinase MB mass (CK-MBm) in early diagnosis of MI using cardiac troponin T (cTnT) positivity as a reference. DESIGN AND METHODS The study population comprised 440 patients who had had chest pain for less than 12 h. Patients were divided into cTnT negative (cTnT-) or cTnT positive (cTnT+) patients (concentration of cTnT >0.1 microg/L at two different time points during 72 h). RESULTS At the time of admission to the emergency department receiver operating characteristics (ROC) curves of CK-MB isoforms and CK-MBm were not better than that of myoglobin. Six hours after admission CK-MB isoforms and CK-MBm provided statistically significantly larger areas under the curve (AUC) than myoglobin (p < 0.01). When ROC curves were related to the onset of chest pain (< 3 h, 3-6 h, and > 6 h) there were no significant differences between the cardiac markers studied. CONCLUSIONS According to the present findings, CK-MB isoforms or myoglobin offer no advantage over CK-MBm as early markers of myocardial infarction.

Aging of the population may not lead to an increase in the numbers of acute coronary events: a community surveillance study and modelled forecast of the future

Objective To examine the incidence, mortality and case fatality of acute coronary syndrome (ACS) in Finland during 1993–2007 and to create forecasts of the absolute numbers of ACS cases in the future, taking into account the aging of the population. Design Community surveillance study and modelled forecasts of the future. Setting and methods Two sets of population-based coronary event register data from Finland (FINAMI and the National Cardiovascular Disease Register (CVDR)). Bayesian age–period–cohort (APC) modelling. Participants 24 905 observed ACS events in the FINAMI register and 364 137 in CVDR. Main outcome measures Observed trends of ACS events during 1993–2007, forecasted numbers of ACS cases, and the prevalence of ACS survivors until the year 2050. Results In the FINAMI register, the average annual declines in age-standardised incidence of ACS were 1.6% (p<0.001) in men and 1.8% (p<0.001) in women. For 28-day case fatality of incident ACS, the average annual declines were 4.1% (p<0.001) in men and 6.7% (p<0.001) in women. Findings in the country-wide CVDR data were consistent with the FINAMI register. The APC model, based on the CVDR data, suggested that both the absolute numbers of ACS events and the prevalence of ACS survivors reached their peak in Finland around 1990, have declined since then, and very likely will continue to decline until 2050. Conclusions The ACS event rates and absolute numbers of cases have declined steeply in Finland. The declining trends are likely to continue in the future despite the aging of the population.

Prognosis of acute coronary events is worse in patients living alone: the FINAMI myocardial infarction register

Background Single living has been associated with a worse prognosis of acute coronary syndrome (ACS). We aimed to study the relation of sociodemographic characteristics to the morbidity, mortality, and case fatality (CF) of ACS in a large population-based ACS register. Methods The population-based FINAMI myocardial infarction register recorded 15,330 cases of ACS among persons aged 35–99 years in Finland in 1993–2002. Record linkage with the files of Statistics Finland provided information on sociodemographic characteristics (marital status, household size). Results ACS incidence and 28-day mortality rate were higher in unmarried men and women in all age groups. The prehospital CF of incident ACS was higher in single living and/or unmarried 35–64-year-old people. The 28-day CF was 26% (95% confidence interval, CI, 24–29%) in married men, 42% (95% CI 37–47%) in men who had previously been married, and 51% (95% CI 46–57%) in never-married men. Among women, the corresponding figures were 20% (95% CI 15–24%), 32% (95% CI 25–39%), and 43% (95% CI 31–56%). Most of these CF differences were apparent already at the prehospital phase. The only difference in treatment was that middle-aged men living alone or unmarried received thrombolysis less often. The disparities in ACS morbidity and mortality by marital status tended to widen during the study period. Conclusions Single living and/or being unmarried increases the risk of having a heart attack and worsens its prognosis both in men and women regardless of age. Most of the excess mortality appears already before the hospital admission and seems not to be related to differences in treatment of ACS.

Troponin T and creatinine kinase isoenzyme MB mass in the diagnosis of myocardial infarction

The aim of this study was to compare troponin T (TnT) and creatine kinase isoenzyme MB mass (CK-MBm) with conventional enzymes, ie CK, CK-MB activity and lactate dehydrogenase isoenzyme 1, in the diagnosis of myocardial infarction (MI). 624 patients (351 men and 273 women, median age 69 years) were admitted to hospital with suspicion of an acute coronary heart disease event. TnT was elevated (> 0.10 microg/L) in 100%, CK-MBm (> 5.0 microg/L) in 99%, and both markers in 99% of the 89 patients with the diagnosis of a definite MI according to modified FINMONICA criteria. In the 60 patients with the diagnosis of a probable MI, TnT was elevated in 65%, CK-MBm in 67% and both markers in 60%. In the patients with unstable coronary artery disease (unstable angina or prolonged chest pain attack) and conventional enzymes within normal limits, TnT was elevated in 14%, CK-MBm in 17% and both markers in 9%. The use of TnT and CK-MBm did not lead to a major change in the diagnostics of definite MI. However, TnT and CK-MBm did not confirm the diagnosis of probable MI in one-third of the events. These new markers revealed a myocardial injury in about 15% of those patients who had unstable coronary artery disease and conventional enzymes within normal limits.

Ruling Out Myocardial Infarction with Troponin T and Creatine Kinase MB Mass: Diagnostic and Prognostic Aspects

OBJECTIVE To investigate the time window for ruling out myocardial infarction (MI) with troponin T (TnT) and creatine kinase isoenzyme MB mass (CK-MBm) and the prognosis of patients with ruled-out MI diagnosis. DESIGN The study was based on 397 patients admitted with a suspected acute coronary syndrome but with relief of symptoms within 24 h. RESULTS MI diagnosis was confirmed with elevated TnT (>0.10 microg/l) in 108 patients. in 91% within 12-24 h from the onset of symptoms, and in 99% within 12 h from admission. In 94 of these patients CK-MBm became elevated (>5.0 microg/l). in 95% within 10-12 h from the onset of symptoms, and in 99% within 6 h from admission. Among patients with ruled-out MI diagnosis, the 1-year incidence of recurrent coronary events was 29% in those with positive history of coronary heart disease (CHD) but only 7% in those without prior CHD (p < 0.001). CONCLUSION Using TnT or CK-MBm, MI can be ruled out within 12 h from admission in the majority of patients. Among patients with ruled-out MI diagnosis, positive history of CHD is an important determinant of prognosis.Objective - To investigate the time window for ruling out myocardial infarction (MI) with troponin T (TnT) and creatine kinase isoenzyme MB mass (CK-MBm) and the prognosis of patients with ruled-out MI diagnosis. Design - The study was based on 397 patients admitted with a suspected acute coronary syndrome but with relief of symptoms within 24 h. Results - MI diagnosis was confirmed with elevated TnT (> 0.10 µg/l) in 108 patients, in 91% within 12-24 h from the onset of symptoms, and in 99% within 12 h from admission. In 94 of these patients CK-MBm became elevated (> 5.0 µg/l), in 95% within 10-12 h from the onset of symptoms, and in 99% within 6 h from admission. Among patients with ruled-out MI diagnosis, the 1-year incidence of recurrent coronary events was 29% in those with positive history of coronary heart disease (CHD) but only 7% in those without prior CHD ( p < 0.001). Conclusion - Using TnT or CK-MBm, MI can be ruled out within 12 h from admission in the majority of patients. Among patients with ruled-out MI diagnosis, positive history of CHD is an important determinant of prognosis.

Decreased mortality risk due to first acute coronary syndrome in women with postmenopausal hormone therapy use

OBJECTIVES The role of postmenopausal hormone therapy (HT) in the incidence of acute coronary syndrome (ACS) has been studied extensively, but less is known of the impact of HT on the mortality risk due to an ACS. STUDY DESIGN AND MAIN OUTCOME MEASURES We extracted from a population-based ACS register, FINAMI, 7258 postmenopausal women with the first ACS. These data were combined with HT use data from the National Drug Reimbursement Register; 625 patients (9%) had used various HT regimens. The death risks due to ACS before admission to hospital, 2-28, or 29-365days after the incident ACS were compared between HT users and non-users with logistic regression analyses. RESULTS In all follow-up time points, the ACS death risks in HT ever-users were smaller compared to non-users. Of women with HT ever use, 42% died within one year as compared with 52% of non-users (OR 0.62, p<0.001). Most deaths (84%) occurred within 28days after the ACS, and in this group 36% of women with ever use of HT (OR 0.73, p=0.002) and 30% of women with ≥5year HT use (OR 0.54, p<0.001) died as compared to 43% of the non-users. Age ≤60 or >60 years at the HT initiation was accompanied with similar reductions in ACS mortality risk. CONCLUSIONS Postmenopausal HT use is accompanied with reduced mortality risk after primary ACS.