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Background and Aims: Both blood pressure and C-reactive protein (CRP) are individually associated with cardiovascular mortality risk. However, the combined effect of systolic blood pressure (SBP) and CRP on coronary heart disease (CHD) and cardiovascular disease (CVD) mortality risk, has not been studied., Methods and Results: We evaluated the joint impact of SBP and CRP and the risk of mortality in the Kuopio Ischemic Heart Disease prospective cohort study of 1622 men aged 42-61 years at recruitment with no history of CVD. SBP and CRP were measured. SBP was categorized as low and high (cut-off 135 mmHg) and CRP as low and high (cut-off 1.54 mg/L) based on ROC curves. Multivariable adjusted hazard ratios (HRs) with confidence intervals (CI) were calculated. During a median follow-up of 28 years, 196 cases of CHD and 320 cases of CVD deaths occurred. Elevated SBP (>135 mmHg) combined with elevated (CRP >1.54 mg/L) were associated with CHD and CVD mortality (HR 3.41, 95% CI, 2.20-5.28, p < 0.001) and (HR 2.93, 95% CI, 2.11-4.06, p < 0.001) respectively after adjustment for age, examination year, smoking, alcohol consumption, BMI, Type 2 diabetes, energy expenditure, total cholesterol, serum HDL cholesterol, antihypertensive medication and use of aspirin., Conclusion: The combined effect of both high systolic blood pressure and high CRP is associated with increased risk of future CHD and CVD mortality as compared with both low SBP and low CRP levels in general male Caucasian population., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Inverted T waves in the electrocardiogram (ECG) have been associated with coronary heart disease (CHD) and mortality. The pathophysiology and prognostic significance of T-wave inversion may differ between different anatomical lead groups, but scientific data related to this issue is scarce., Methods: A representative sample of Finnish subjects (n = 6,354) aged over 30 years underwent a health examination including a 12-lead ECG in the Health 2000 survey. ECGs with T-wave inversions were divided into three anatomical lead groups (anterior, lateral, and inferior) and were compared to ECGs with no pathological T-wave inversions in multivariable-adjusted Fine-Gray and Cox regression hazard models using CHD and mortality as endpoints., Results: The follow-up for both CHD and mortality lasted approximately fifteen years (median value with interquartile ranges between 14.9 and 15.3). In multivariate-adjusted models, anterior and lateral (but not inferior) T-wave inversions associated with increased risk of CHD (HR: 2.37 [95% confidence interval 1.20-4.68] and 1.65 [1.27-2.15], respectively). In multivariable analyses, only lateral T-wave inversions associated with increased risk of mortality in the entire study population (HR 1.51 [1.26-1.81]) as well as among individuals with no CHD at baseline (HR 1.59 [1.29-1.96])., Conclusions: The prognostic information of inverted T waves differs between anatomical lead groups. T-wave inversion in the anterior and lateral lead groups is independently associated with the risk of CHD, and lateral T-wave inversion is also associated with increased risk of mortality. Inverted T wave in the inferior lead group proved to be a benign phenomenon., (© 2020 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Background and Aims: In the 1960s and 1970s, Finland, mortality due to coronary heart disease (CHD) was over 30% higher among Finns residing in the east of the country compared with those residing in the west. Today, CHD mortality remains 20% higher among eastern Finns. The higher incidence of CHD mortality among eastern Finns has largely been explained by higher risk factor levels. Using a unique longitudinal cohort, we aimed to determine if participants who resided in eastern Finland during childhood had higher CHD risk factors in adulthood and from childhood to adulthood., Methods: The study population included 2063 participants of the Cardiovascular Risk in Young Finns Study, born during the period 1962-1977, with risk factor data available from baseline (1980) when participants were aged 3-18 years, and had risk factor data collected again in adulthood (2011) when aged 34-49 years., Results: Adult CHD risk factor profile was similar for those who resided in eastern or western Finland in childhood. Over life-course from 1980 to 2011, those subjects with childhood residency in eastern Finland had, on average, higher systolic (p = 0.006) and diastolic (p = 0.0009) blood pressures, total (p = 0.01) and LDL-cholesterol (p = 0.01), triglycerides (p = 0.04), apoB (p = 0.02), and serum glucose (p < 0.0001) than those who resided in western Finland in childhood., Conclusions: Our sample of adult Finns aged 34-49 years had a similar CHD risk factor profile irrespective of whether they resided in eastern or western Finland during their childhood. However, when considering participants risk factor profiles over a 31-year period, those who resided in eastern Finland in childhood were associated with a less favorable CHD risk factor profile than those who resided in western Finland in childhood. The observed differences suggest that future CHD mortality might remain higher in eastern Finland compared with western Finland., (Copyright © 2018. Published by Elsevier B.V.)

Objective: It is well established that diabetic nephropathy increases the risk of cardiovascular disease (CVD), but how severe diabetic retinopathy (SDR) impacts this risk has yet to be determined., Research Design and Methods: The cumulative incidence of various CVD events, including coronary heart disease (CHD), peripheral artery disease (PAD), and stroke, retrieved from registries, was evaluated in 1,683 individuals with at least a 30-year duration of type 1 diabetes drawn from the Finnish Diabetic Nephropathy Study (FinnDiane). The individuals were divided into four groups according to the presence of diabetic kidney disease (DKD) and/or SDR (+DKD/+SDR, +DKD/-SDR, -DKD/+SDR, and -DKD/-SDR) at baseline visit. Furthermore, age-specific incidences were compared with 4,016 control subjects without diabetes. SDR was defined as laser photocoagulation and DKD as estimated glomerular filtration rate <60 mL/min/1.73 m 2 ., Results: During 12,872 person-years of follow-up, 416 incident CVD events occurred. Even in the absence of DKD, SDR increased the risk of any CVD (hazard ratio 1.46 [95% CI 1.11-1.92]; P < 0.01), after adjustment for diabetes duration, age at diabetes onset, sex, smoking, blood pressure, waist-to-hip ratio, history of hypoglycemia, and serum lipids. In particular, SDR alone was associated with the risk of PAD (1.90 [1.13-3.17]; P < 0.05) and CHD (1.50 [1.09-2.07; P < 0.05) but not with any stroke. Moreover, DKD increased the CVD risk further (2.85 [2.13-3.81]; P < 0.001). However, the risk was above that of the control subjects without diabetes also in patients without microvascular complications, until the patients reached their seventies., Conclusions: SDR alone, even without DKD, increases cardiovascular risk, particularly for PAD, independently of common cardiovascular risk factors in long-standing type 1 diabetes. More remains to be done to fully understand the link between SDR and CVD. This knowledge could help combat the enhanced cardiovascular risk beyond currently available regimens., (© 2018 by the American Diabetes Association.)

Background and Aims: While inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) is known to result in dramatic lowering of LDL-cholesterol (LDL-C), it is poorly understood how it affects other lipid species and their metabolism. The aim of this study was to characterize the alterations in the lipidome of plasma and lipoprotein particles after administration of PCSK9 inhibiting antibody to patients with established coronary heart disease., Methods: Plasma samples were obtained from patients undergoing a randomized placebo-controlled phase II trial (EQUATOR) for the safe and effective use of RG7652, a fully human monoclonal antibody inhibiting PCSK9 function. Lipoprotein fractions were isolated by sequential density ultracentrifugation, and both plasma and major lipoprotein classes (VLDL-IDL, LDL, HDL) were subjected to mass spectrometric lipidomic profiling., Results: PCSK9 inhibition significantly decreased plasma levels of several lipid classes, including sphingolipids (dihydroceramides, glucosylceramides, sphingomyelins, ceramides), cholesteryl esters and free cholesterol. Previously established ceramide ratios predicting cardiovascular mortality, or inflammation related eicosanoid lipids, were not altered. RG7652 treatment also affected the overall and relative distribution of lipids in lipoprotein classes. An overall decrease of total lipid species was observed in LDL and VLDL + IDL particles, while HDL-associated phospholipids increased. Following the treatment, LDL displayed reduced lipid cargo, whereas relative lipid proportions of the VLDL + IDL particles were mostly unchanged, and there were relatively more lipids carried in the HDL particles., Conclusions: Administration of PCSK9 antibody significantly alters the lipid composition of plasma and lipoprotein particles. These changes further shed light on the link between anti-PCSK9 therapies and cardiovascular risk., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Aims: Clinical experience and observational studies suggest that individuals with coeliac disease are at increased risk of coronary heart disease (CHD), but the precise mechanism for this is unclear. Laboratory studies suggest that it may relate to tissue transglutaminase antibodies (tTGAs). Our aim was to examine whether seropositivity for tTGA and endomysial antibodies (EMAs) are associated with incident CHD in humans., Methods and Results: We used data from Mini-Finland Health Survey, a prospective cohort study of Finnish men and women aged 35-80 at study baseline 1978-80. TTGA and EMA seropositivities were ascertained from baseline blood samples and incident CHD events were identified from national hospitalisation and death registers. Cox regression was used to examine the associations between antibody seropositivity and incident CHD. Of 6887 men and women, 562 were seropositive for tTGAs and 72 for EMAs. During a median follow-up of 26 years, 2367 individuals experienced a CHD event. We found no clear evidence for an association between tTGA positivity (hazard ratio, HR: 1.04, 95% confidence interval, CI: 0.83, 1.30) or EMA positivity (HR: 1.16, 95% CI: 0.77, 1.74) and incident CHD, once pre-existing CVD and known CHD risk factors had been adjusted for., Conclusion: We found no clear evidence for an association of tTGA or EMA seropositivity with incident CHD outcomes, suggesting that tTG autoimmunity is unlikely to be the biological link between coeliac disease and CHD., (Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Introduction: Obstructive sleep apnea (OSA) has been associated with an elevated rate of cardiovascular mortality. However, this issue has not been investigated in patients with elevated proneness to cardiovascular diseases. Our hypothesis was that OSA would have an especially adverse effect on the risk of cardiovascular mortality in Finnish individuals exhibiting elevated proneness for coronary heart diseases., Methods: Ambulatory polygraphic recordings from 405 men having suspected OSA were retrospectively analyzed. The patients were categorized regarding sleep disordered breathing into a normal group (apnea hypopnea index (AHI) < 5, n = 104), mild OSA group (5 ≤ AHI < 15, n = 100), and moderate to severe OSA group (AHI ≥ 15, n = 201). In addition, basic anthropometric and health data were collected. In patients who died during the follow-up period (at least 12 years and 10 months), the primary and secondary causes of death were recorded., Results: After adjustment for age, BMI, and smoking, the patients with moderate to severe OSA suffered significantly (p < 0.05) higher mortality (hazard ratio 3.13) than their counterparts with normal recordings. The overall mortality in the moderate to severe OSA group was 26.4 %, while in the normal group it was 9.7 %. Hazard ratio for cardiovascular mortality was 4.04 in the moderate to severe OSA and 1.87 in the mild OSA group., Conclusions: OSA seems to have an especially adverse effect on the cardiovascular mortality of patients with an elevated genetic susceptibility to coronary heart diseases. When considering that all our patients had possibility of continuous positive airway pressure treatment and our reference group consisted of patients suffering from daytime somnolence, the hazard ratio of 4.04 for cardiovascular mortality in patients with moderate to severe disease is disturbingly high.

Objective: Genome-wide association studies have identified several genetic variants associated with coronary heart disease (CHD). The aim of this study was to evaluate the genetic risk discrimination and reclassification and apply the results for a 2-stage population risk screening strategy for CHD., Approach and Results: We genotyped 28 genetic variants in 24 124 participants in 4 Finnish population-based, prospective cohorts (recruitment years 1992-2002). We constructed a multilocus genetic risk score and evaluated its association with incident cardiovascular disease events. During the median follow-up time of 12 years (interquartile range 8.75-15.25 years), we observed 1093 CHD, 1552 cardiovascular disease, and 731 acute coronary syndrome events. Adding genetic information to conventional risk factors and family history improved risk discrimination of CHD (C-index 0.856 versus 0.851; P=0.0002) and other end points (cardiovascular disease: C-index 0.840 versus 0.837, P=0.0004; acute coronary syndrome: C-index 0.859 versus 0.855, P=0.001). In a standard population of 100 000 individuals, additional genetic screening of subjects at intermediate risk for CHD would reclassify 2144 subjects (12%) into high-risk category. Statin allocation for these subjects is estimated to prevent 135 CHD cases over 14 years. Similar results were obtained by external validation, where the effects were estimated from a training data set and applied for a test data set., Conclusions: Genetic risk score improves risk prediction of CHD and helps to identify individuals at high risk for the first CHD event. Genetic screening for individuals at intermediate cardiovascular risk could help to prevent future cases through better targeting of statins.

Background: Low intellectual ability is associated with an increased risk of coronary heart disease and stroke. Most studies have used a general intelligence score. We studied whether three different subscores of intellectual ability predict these disorders., Methods: We studied 2,786 men, born between 1934 and 1944 in Helsinki, Finland, who as conscripts at age 20 underwent an intellectual ability test comprising verbal, visuospatial (analogous to Raven's progressive matrices) and arithmetic reasoning subtests. We ascertained the later occurrence of coronary heart disease and stroke from validated national hospital discharge and death registers., Results: 281 men (10.1%) had experienced a coronary heart disease event and 131 (4.7%) a stroke event. Coronary heart disease was predicted by low scores in all subtests, hazard ratios for each standard deviation (SD) lower score ranging from 1.21 to 1.30 (confidence intervals 1.08 to 1.46). Stroke was predicted by a low visuospatial reasoning score, the corresponding hazard ratio being 1.23 (95% confidence interval 1.04 to 1.46), adjusted for year and age at testing. Adjusted in addition for the two other scores, the hazard ratio was 1.40 (1.10 to 1.79). This hazard ratio was little affected by adjustment for socioeconomic status in childhood and adult life, whereas the same adjustments attenuated the associations between intellectual ability and coronary heart disease. The associations with stroke were also unchanged when adjusted for systolic blood pressure at 20 years and reimbursement for adult antihypertensive medication., Conclusions: Stroke is predicted by low visuospatial reasoning scores in relation to scores in the two other subtests. This association may be mediated by common underlying causes such as impaired brain development, rather than by mechanisms associated with risk factors shared by stroke and coronary heart disease, such as socio-economic status, hypertension and atherosclerosis.

Background: Self-reported angina symptoms are collected in epidemiological surveys. We aimed at validating the angina symptoms assessed by the Rose Questionnaire against registry data on coronary heart disease. A further aim was to examine the sex paradox in angina implying that women report more symptoms, whereas men have more coronary events., Design: Angina symptoms of 6601 employees of the City of Helsinki were examined using the postal questionnaire survey data combined with coronary heart disease registries., Methods: The self-reported angina was classified as no symptoms, atypical pain, exertional chest pain, and stable angina symptoms. Reimbursed medications and hospital admissions were available from registries 10 years before the survey. Binomial regression analysis was used., Results: Stable angina symptoms were associated with hospital admissions and reimbursed medications [prevalence ratio (PR), 6.75; 95% confidence interval (CI), 4.56-9.99]. In addition, exertional chest pain (PR, 5.31; 95% CI, 3.45-8.18) was associated with coronary events. All events were more prevalent among men than women (PR, 2.36; 95% CI, 1.72-3.25)., Conclusion: The Rose Questionnaire remains a valid tool to distinguish healthy people from those with coronary heart disease. However, a notable part of those reporting symptoms have no confirmation of coronary heart disease in the registries. The female excess of symptoms and male excess of events may reflect inequality or delay in access to treatment, problems in identification and diagnosis, or more complex issues related to self-reported angina symptoms.

Aims: Information on medicine use among coronary heart disease (CHD) patients with diabetes in unselected patient populations is scarce. This study examines the use of medication to prevent new cardiac events among newly diagnosed CHD patients with diabetes comparing them to patients without diabetes and examines socioeconomic differences in medicine use in these patient groups., Methods: Data on CHD patients (43,501 men and 31,125 women) with or without diabetes were individually linked from nationwide registers (covering both patients treated in ambulatory and in hospital inpatient care). Age-standardised rates for medication use were calculated and differences between patient groups examined using Poisson regression., Results: beta-blocker use was high in all patient groups in 1997-2002, angiotensin-converting enzyme (ACE) inhibitor and angiotensin II antagonist use increased and remained higher among patients with diabetes. More than half of men and women with diabetes used ACE inhibitors and one out of five used angiotensin II antagonists in 2002. Lipid-lowering medication use increased, especially among women. In 1997-98 it was lower in lower socioeconomic groups; among men with diabetes the use remained lower than among others., Conclusions: beta-blocker use was constant and ACE inhibitor and angiotensin II antagonist use increased. Lipid-lowering medication use increased considerably after a health insurance reform in 2000, in which elevated reimbursement of drug costs (75%) was extended to include all CHD patients with hyperlipidaemia.Socioeconomic differences in medication use disappeared after the reform. However, lipid-lowering medication use remained at a lower level among men with diabetes, suggesting that their treatment did not follow guidelines.

Objective: To investigate coronary heart disease (CHD) morbidity and mortality and their patterning by socioeconomic status among diabetic and nondiabetic individuals in Finland., Methods: All diabetic persons aged 35-74 years entitled to free anti-diabetic medication were drawn from the 1991-1996 national health insurance files along with nondiabetic referents. Outcome events for up to 6 years of follow-up, corresponding to 418,987 and 867,813 person-years in diabetic and nondiabetic people, respectively, were identified from national health insurance, hospital discharge and causes of death registers using personal identification codes., Results: The annual CHD incidence for diabetic women and men was 2.7% and 3.7%, respectively, corresponding to relative risks of 3.55 (95% CI: 3.43-3.67) and 2.64 (95% CI: 2.56-2.72) compared to nondiabetic persons. The impact of diabetes on CHD mortality was greater, with relative death rates of 6.04 and 3.42 for women and men, respectively. CHD mortality and incidence displayed systematic socioeconomic trends with higher rates among worse-off diabetic and nondiabetic people, although gradients were generally steeper for nondiabetics. In the diabetic population, socioeconomic differences were rather similar for sudden CHD deaths and nonfatal CHD incident cases. For both genders, socioeconomic differences in mortality after CHD diagnosis were small in both diabetic and nondiabetic persons, except for the lowest compared to the highest income quintile., Conclusions: Socioeconomic CHD mortality differences among diabetic people in Finland were mainly explained by higher CHD incidence and particularly sudden deaths without prior CHD diagnosis. No systematic socioeconomic differences were found in long-term prognosis after CHD diagnosis.

Background: Most cohort studies have found depressive symptoms to be associated with increased cardiovascular mortality in the elderly, but follow-up times have often been short and study populations small., Objectives: To describe associations between stronger symptoms of depression and the risk of death from coronary heart disease (CHD) or myocardial infarction (MI) in elderly Finnish subjects free of CHD at the baseline., Methods: This study is a prospective population-based epidemiological and clinical twelve-year follow-up study in Lieto Health Centre, Finland. The basic population consisted of 1196 elderly (64 years of age or older) persons who lived in the municipality of Lieto in southwestern Finland in 1990. The occurrence of CHD was determined on the basis of electrocardiographic (ECG) findings, Rose questionnaire and the diagnoses in medical records. The persons with CHD were excluded from the study population. Symptoms of depression at the baseline were measured with the Zung Self-rating Depression Scale (ZSDS). Mortality was followed up for about 12 years., Results: The Kaplan-Meier survival curves showed stronger symptoms of depression to be related to high risks of mortality from CHD or MI among men and women. According to the Cox model for men significant predictors for higher risk of CHD or MI mortality were stronger symptoms of depression, higher age and a large number of medications in use. When women were examined, significant predictors were stronger symptoms of depression and a large number of medications in use., Conclusions: Stronger symptoms of depression are an independent risk factor for high CHD or MI mortality in aged Finnish men and women free of CHD at baseline.

Background and Design: The recent introduction of sensitive markers of myocardial injury is likely to affect the epidemiology of coronary heart disease (CHD). The American Heart Association together with other societies and research agencies have recently published a new definition on acute CHD to improve consistency in epidemiological and clinical studies (referred here as the '2003 definition')., Methods: In this study we compare the data on CHD events in the Finnish National Hospital Discharge Register (HDR) and the Causes of Death Register (CDR) with the population-based myocardial infarction (MI) register, FINMONICA/FINAMI. The FINMONICA/FINAMI events were classified according to the 2003 definition. The relevant International Classification of Diseases (ICD) codes from the HDR and CDR were used., Results: Using the 2003 definition as the reference, the overall sensitivity of the ICD codes for MI in the combined HDR and CDR was 83% and the positive predictive value (PPV) was 90%. When the ICD codes for unstable angina were added to the analyses, the sensitivity improved to 85% and the PPV declined to 83%. In the age group 35-74 the sensitivity of the MI codes improved over time, in men from 64% in 1988-1992 to 81% in 1998-2002, and in women from 61 to 78%, respectively. The oldest age group, 75 years or older, had sensitivity and PPV values comparable to those of the younger., Conclusion: Diagnoses of fatal and non-fatal CHD events in the Finnish HDR and Causes of Death register were reasonably valid indicators for hard CHD events when compared with the FINMONICA/FINAMI register data.

Common chronic infections including those caused by cytomegalovirus (CMV), herpes simplex viruses (HSV), Helicobacter pylori and Chlamydia pneumoniae have previously been related to increased risk of coronary heart disease (CHD). We investigated the association between serology of these chronic infections and coronary bypass graft occlusions in 61 patients. As a result, IgG seropositivity rate against H. pylori was higher among patients without occlusion (82%) than in those with occlusion (45%) or apparently healthy controls (57%) (p = 0.004 and p = 0.008, respectively). In conclusion, H. pylori infection, as judged by IgG seropositivity, is associated with lower occurrence of venous bypass graft occlusion in patients with CHD and may thus be connected with better outcome and prognosis of CHD patients after bypass graft surgery.

The aim of this study was to investigate factors associated with life dissatisfaction in symptomatic patients (n = 144) with chest pain subsequently diagnosed as coronary heart disease (CHD) by coronary angiography. Life dissatisfaction was assessed with a four-item life satisfaction scale (LS), depression with the 21-item Beck Depression Inventory (BDI) and other psychiatric symptoms with the symptom check list (SCL). DSM-III-R Axis I and Axis II psychiatric diagnoses were performed by means of the Structured Clinical Interview. All assessments took place one day before angiography. Twenty-four per cent of CHD patients were dissatisfied with their lives. Life dissatisfaction was associated with being unmarried. Dissatisfied patients had Axis I mental disorders and Axis II personality disorders more frequently than others. Psychiatric and depressive symptoms according to the SCL and BDI, respectively, were also higher among dissatisfied patients. In multiple logistic regression analyses, mental disorders were related to life dissatisfaction when age, sex, employment status, New York Heart Association class, duration of chest pain symptoms and work load were controlled in the model. Married subjects had a lower probability of being dissatisfied with their lives than other subjects (Odds Ratio, OR: 0.23). When BDI scores were included in the model, the only factor independently associated with life dissatisfaction was the severity of depressive symptoms (OR: 1.81). To conclude, life dissatisfaction is not primarily determined by the severity of CHD but by the existence of depressive symptoms.

Background: Risk stratification in troponin (cTn)-negative acute coronary syndrome (ACS) remains a clinical challenge. We investigated the predictive value of circulating pregnancy-associated plasma protein A (PAPP-A), a novel marker of atherosclerotic plaque activity, in these patients., Methods and Results: Two hundred consecutive hospitalized ACS patients were included, of whom 136 (69 men and 67 women; mean+/-SD age, 66+/-16 years) remained cTnI-negative for up to 24 hours. PAPP-A was measured at admission, 6 to 12 hours, and 24 hours. During 6-month follow-up, 26 (19.1%) of the cTnI-negative patients reached a primary end point (cardiovascular death, myocardial infarction, or revascularization). At a cutoff level of 2.9 mIU/L, elevated PAPP-A was an independent predictor of adverse outcome (adjusted risk ratio [RR], 4.6; 95% confidence interval, 1.8 to 11.8; P=0.002). Another independent predictor was admission CRP >2.0 mg/L (RR, 2.6; P=0.03)., Conclusions: Measurement of plasma PAPP-A, a zinc-binding matrix metalloproteinase, is a strong independent predictor of ischemic cardiac events and need of revascularization in patients who present with suspected myocardial infarction but remain troponin negative.

Mortality rates from coronary heart disease are lower in Swedish men and among Finnish migrants who have lived in Sweden for over 20 years than in men living in Finland. Sero-epidemiological studies, investigations of atheromatous plaque specimens, in vitro animal models and anti-chlamydial antibiotic trials have given support to the hypothesis that Chlamydia pneumoniae (Cpn) has a role in atherosclerosis. We investigated whether men with a similar genetic background but living permanently in Finland or Sweden have differences in the prevalence of Cpn seropositivity, and whether chronic Cpn infection is associated with markers of subclinical atherosclerosis. We measured anti-Cpn antibodies and ultrasonographic markers of subclinical atherosclerosis, including carotid intima-media thickness, carotid artery compliance and brachial artery flow-mediated dilatation, in a population of 76 migrant-discordant male twin pairs (152 men). The number of men with seropositivity to Cpn infection (defined as IgA>/=1:64 and IgG>/=1:128) was greater in Finland than in Sweden (21.5% compared with 10.5%; P =0.046). Cpn seropositivity accompanied by elevated C-reactive protein (CRP) levels (>1 mg/l) was associated with attenuated brachial artery flow-mediated dilatation (3.3+/-0.3%, compared with 5.5+/-0.4% in men with no signs of Cpn infection; P <0.001).Thus, among Finnish twin brothers discordant for migration to Sweden, the prevalence of Cpn seropositivity is higher for those living in Finland, and men with Cpn seropositivity combined with elevated CRP levels had attenuated endothelial function. These findings offer insight into the mechanism whereby chronic Cpn infection may increase the risk of coronary heart disease.

Objective: To evaluate how new treatment guidelines of acute coronary syndrome (ACS) without ST elevation have been implemented into clinical practice in Finland., Design: A prospective survey on 501 consecutive patients (mean age 68 [range 27-96] years) admitted to nine hospitals in Finland with suspected ACS without persistent ST elevation between January and March 2001., Results: The rate of death was 4.2% in hospital and 9.8% at 6 months. Six-month composite incidence of death, new myocardial infarction, refractory angina or readmission for unstable angina was 25.4%. The majority of patients had beta-blocker and aspirin both in hospital and at 6 months. Low molecular weight heparin was used in 76% of patients. Statins were used in 52% of patients in hospital and in 64% at 6 months. Glycoprotein (GP) IIb/IIIa receptor antagonists were used in 18% of all patients. The overall rate of coronary angiography was 40% in hospital and 54% at 6 months, but there was large interhospital variation. Overall, only 45% of very high-risk patients underwent angiography during initial hospitalization. Very high-risk patients had longer waiting times for angiography than low-risk patients (5.8 vs 4.5 days, p < 0.05)., Conclusion: Traditional medication with aspirin and beta-blocker is widely used in ACS, whereas statins, GPIIb/IIIa receptor antagonists and invasive therapy are underused. Well-known risk factors were poor predictors of receiving in-hospital angiography. Implementation of new ESC guidelines into clinical practice needs further education and more resources.

Background: Daily variations in ambient particulate air pollution have been associated with cardiovascular mortality and morbidity. We therefore assessed the associations between levels of the 3 main modes of urban aerosol distribution and the occurrence of ST-segment depressions during repeated exercise tests., Methods and Results: Repeated biweekly submaximal exercise tests were performed during 6 months among adult subjects with stable coronary heart disease in Helsinki, Finland. Seventy-two exercise-induced ST-segment depressions >0.1 mV occurred during 342 exercise tests among 45 subjects. Simultaneously, particle mass <2.5 microm (PM2.5) and the number concentrations of ultrafine particles (particle diameter 10 to 100 nm [NC(0.01-0.1)]) and accumulation mode particles (100 to 1000 nm [NC(0.1-1)]) were monitored at a central site. Levels of particulate air pollution 2 days before the clinic visit were significantly associated with increased risk of ST-segment depression during exercise test. The association was most consistent for measures of particles reflecting accumulation mode particles (odds ratio 3.29; 95% CI, 1.57 to 6.92 for NC(0.1-1) and 2.84; 95% CI, 1.42 to 5.66 for PM2.5), but ultrafine particles also had an effect (odds ratio 3.14; 95% CI, 1.56 to 6.32), which was independent of PM2.5. Also, gaseous pollutants NO2 and CO were associated with an increased risk for ST-segment depressions. No consistent association was observed for coarse particles. The associations tended to be stronger among subjects who did not use beta-blockers., Conclusions: The present results suggest that the effect of particulate air pollution on cardiovascular morbidity is at least partly mediated through increased susceptibility to myocardial ischemia.

We compared the diagnoses obtained from the routine mortality statistics with the standardized World Health Organization (WHO) MONICA (multinational MONItoring of trends and determinants in CArdiovascular disease) classification in suspect coronary heart disease (CHD) deaths registered in the FINMONICA myocardial infarction (MI) register during 1983-1992. All CHD deaths from routine mortality statistics (International Classification of Diseases codes 410-414) were registered in the MI register. Of the CHD deaths in routine mortality statistics 1.7% in men and 4.8% in women did not fulfill the MONICA criteria for CHD death (P<0.001 for the difference between the sexes). In men 4.7% and in women 7.3% (P=0.004) of the deaths registered in the MI Register and classified as CHD deaths by MONICA criteria had another underlying cause of death than CHD in routine mortality statistics; this proportion increased over time in both sexes (P=0.002 in men and P=0.77 in women). The CHD mortality trends obtained separately from the routine mortality statistics and from the FINMONICA MI Register were very similar. In conclusion, the high CHD mortality in Finland reported by the routine mortality statistics is real. It is possible that some CHD deaths have escaped registration, but the decline seen in the CHD mortality is also real.

We analysed to what extent cardiovascular risk factors may explain the observed difference in the risk of coronary heart disease (CHD) between two areas with markedly different CHD incidence. The study included 7049 men aged 25-64 years who had participated in a baseline survey in 1982 or in 1987 in the Kuopio and North Karelia provinces of eastern Finland and in the Turku-Loimaa region of southwestern Finland. During the baseline surveys the following factors were determined: smoking, blood pressure, cholesterol, high-density lipoprotein cholesterol, diabetes, height, body mass index, family history of CHD and socioeconomic status. The cohorts were followed for coronary events until the end of 1994. CHD risk was about 40% higher in eastern than in southwestern Finland. The levels of most of the measured risk factors were also higher in eastern Finland. Differences in risk factor levels explained about 40% of the excess CHD risk in eastern Finland. The impact of the classical risk factors, such as smoking, cholesterol and blood pressure, on the regional difference was smaller than expected. Single risk factor measurements in our population surveys, however, may not have correctly reflected the long-term exposure of individuals to these risk factors, particularly because the surveys were carried out within a period during which these risk factors were undergoing favourable changes in the Finnish population. In addition to the classical risk factors, regional differences in body height and socioeconomic status were associated with the regional differences in CHD risk.

Objectives: To study self-rated and physician-rated health, to analyse concordance of the two methods and to examine factors explaining differences between self-rated and physician-rated health., Design: Population-based cross-sectional study., Setting: Finnish cohorts of the Seven Countries Study., Subjects: 470 men aged 70-89 years., Main Outcome Measures: Self-administered questionnaire and clinical examination., Results: General health status estimated by doctors correlated weakly with self-rated health. The strongest determinants of self-rated health were depression (P < 0.0001), coronary heart disease (P = 0.0112) and dysuria (P = 0.0238). Activity of daily living (P < 0.0001), age (P = 0.0001), coronary heart disease (P = 0.0005) and chronic lung disease (P = 0.0064) were independently related to physician-rated health., Conclusion: The discrepancy found in ratings of health between physicians and the subjects themselves can be explained by different appreciation of ageing in the assessment of health status. After adjustment for medical conditions, age did not relate to self-perceived health, whereas there was a significant association between age and doctors' ratings. Depression and symptoms which explained self-ratings were not related to physicians' assessments.

We validated diagnoses of acute myocardial infarction (AMI) and death from coronary heart disease (CHD) found in the Finnish National Hospital Discharge Register and the Register of Causes of Death from a sample of the 29,133 men participating in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The cases were traced to hospitals and institutes performing medico-legal death cause examinations and all relevant information was collected. The cardiac events were re-evaluated according to the diagnostic criteria of the Finnish contribution to the WHO MONICA project, i.e. the FINMONICA criteria. Altogether 408 cases of non-fatal AMI (n = 217) and death from CHD (n = 191) were reviewed. In the re-evaluation 94% of them (95% confidence interval 92-96%) were diagnosed as either definite (57%) or possible (37%) AMI. Non-fatal cases were more often classified definite AMI in the review, whereas fatal cases were more often classified possible AMI. Age or trial supplementation group did not affect classification, and no secular trend was observed. In conclusion, the diagnoses of AMI and death from CHD in the registers were highly predictive of a true major coronary event defined by strict criteria, thus their use in endpoint assessment in epidemiological studies and clinical trials is justified.

A number of psychosomatic studies have suggested that alexithymia, impairment in identifying and expressing inner feelings, might somehow affect the course of various illnesses. However, none of these studies have distinguished between an impact of alexithymia on actual pathophysiological change versus an impact only on illness behavior. In the present study, a population-based random sample of 2297 middle-aged men from Eastern Finland was evaluated for alexithymia using the Finnish version of the self-report Toronto Alexithymia Scale (TAS). Although high TAS scores were associated with prior diagnosis of coronary heart disease (CHD), they were not associated with greater prevalence of ischemia on an exercise tolerance test. The results of B-mode ultrasonography of the carotid artery for those who had a CHD diagnosis showed that carotid atherosclerosis actually decreased significantly as alexithymia increased. An interaction analysis indicated that alexithymia was related to increased probability of being diagnosed with CHD only among those who had mildly or moderately progressed carotid atherosclerosis, and not among those with the most severe progression. Alexithymia was associated with higher perceived exertion, and to some extent, with more self-reported symptoms during the exercise tolerance test. The findings support the hypothesis that alexithymia relates to increased symptom reporting rather than pathophysiological changes in CHD. The results also suggest that alexithymic men may get diagnosed earlier, perhaps because of their different illness behavior.

The prevalence of coronary heart disease (CHD), cardiovascular disease (CVD) and associated risk factors was studied in 413 men aged 70-89, the survivors of the Finnish cohorts of the Seven Countries Study. Men were divided into five categories according to manifestations of prevalent CVD: I, history or ECG evidence of previous myocardial infarction (MI; 48 men, 12%); II, typical angina pectoris (AP; 56 men, 14%); III, other ischaemic electrocardiographic (ECG) changes (82 men, 20%); IV, stroke, transient ischaemic attack, intermittent claudication or minor ECG changes (other CVD; 78 men, 19%); V, free of CVD (149 men, 36%). Both systolic and diastolic blood pressures were lowest in men with previous MI and in men free of CVD, and highest in men with other ischaemic ECG changes (P = 0.017). Low HDL-cholesterol (< 0.9 mmol/l) was more prevalent and the total/HDL-cholesterol ratio and triglyceride levels were higher in men with prevalent CHD (P < 0.05). Total and LDL-cholesterol, smoking, body mass index, fibrinogen, coagulation factor VIIc, apolipoprotein A-I, apolipoprotein B and lipoprotein(a) were not associated with prevalent CVD. The results show that manifestations of CHD and CVD are common among elderly Finnish men. Low HDL-cholesterol, total/HDL ratio, triglycerides and hypertension were associated with manifest CVD cross-sectionally.

The relation between plasma insulin level and the prevalence of coronary heart disease was studied in a representative nondiabetic population sample of 396 men and 673 women aged 65-74 years in Kuopio, eastern Finland, in 1986-1988. No association between plasma insulin levels and the prevalence of previous myocardial infarction was seen, except for a positive relation between 2-hour insulin level and myocardial infarction in women (4.1, 4.1, and 11.9%, p < 0.01; insulin quintiles I+II, III+IV, and V, respectively). However, the prevalence of ischemic electrocardiographic changes increased by quintiles of fasting plasma insulin (not significant) and 2-hour plasma insulin (39.8, 50.6, and 59.5% in men, p < 0.01; 35.9, 39.0, and 53.0% in women, p < 0.01). Furthermore, the prevalence of angina pectoris increased by fasting insulin (19.3, 19.0, and 33.8%, in men, p < 0.05; not significant in women) and 2-hour insulin quintiles (11.2, 28.8, and 30.4% in men, p < 0.001; 17.0, 17.8, and 28.4% in women, p < 0.05). There was a marked clustering of risk factors, including high total triglyceride levels, low high density lipoprotein cholesterol levels, and hypertension in subjects in the highest insulin quintiles. The association between insulin levels and coronary heart disease, except for myocardial infarction in women, diminished in multivariate analyses. In conclusion, hyperinsulinemia was related to an increased prevalence of coronary heart disease in elderly subjects which may be due to in part to adverse alterations in other risk factors associated with hyperinsulinemia.

Clinical assessments of health status and work ability were compared with subjective assessments reported on a questionnaire. The clinical examinations included cardiorespiratory, musculoskeletal, and psychological measurements. The subjective work ability comprised an index based on estimations of work ability in relation to diseases, job demands, and psychological resources. For the clinical examinations 89 male and 85 female workers aged 44-58 years were selected according to health and subjective work ability as reported on the questionnaire. Half of the group was healthy and half suffered from either coronary artery disease (men) or low-back pain (women), and the subjective estimations of work ability varied from good to poor. The results indicated that the questionnaire responses on health and work ability related well with the clinically assessed factors at the group level. Some divergence was detected at the individual level, but it could usually be explained on the basis of the available data.

Objective: To compare the prevalence of silent myocardial ischaemia associated with coronary artery disease in diabetic subjects with that in controls of similar age and sex., Design: A controlled study in which subjects with positive findings on exercise electrocardiography, 24 hour electrocardiographic recording, or dynamic thallium scintigraphy (diabetics only) underwent coronary angiography., Setting: Academic medical centre; referral based cardiology clinic., Subjects: 136 Diabetic subjects, of whom 72 (33 women, 39 men (mean age 46.0] were insulin dependent and 64 (19 women, 45 men (mean age 49.3] non-insulin dependent. 80 Controls matched for age and sex; all were clients of the Occupational Health Service of Oulu University Central Hospital or the State Occupational Health Service Station in Oulu in whom diabetes had been excluded by a glucose tolerance test., Interventions: Any subject showing signs of myocardial ischaemia was referred for cardiac catheterization., Main Outcome Measures: Exercise electrocardiography and 24 hour electrocardiographic recording were regarded as positive if there were ST depressions of greater than or equal to 1 mm that were planar or downsloping and persisted for 0.08 seconds after the J point. Thallium tomographic imaging. With cardiac catheterisation, coronary artery lesions were classified as significant in half or more of the vessel lumen was narrowed, or insignificant if such narrowing was less than half., Results: 40 (29%) diabetes and four (5%) controls had positive results in one or more of the non-invasive tests. Coronary angiography was performed on 34 of the diabetics (six refused); 12 had significant coronary artery narrowing; seven had unimportant atherosclerosis; 15 had patent coronary arteries. Among the controls only one had unimportant atherosclerosis; the other three had patent arteries., Conclusions: These results confirm the high prevalence of asymptomatic myocardial ischaemia in diabetics. Non-invasive screening of diabetic subjects, however, does not seem justified because of the low preset probability of the presence of the disease and the inaccuracy of the available test methods.

The Social Insurance Institution's Coronary Heart Disease Study is a prospective population study designed to investigate the prevalence, risk factors and incidence of coronary heart disease (CHD) in middle-aged Finnish men and women. The study population consisted of 5 738 men and 5 224 women, aged 30-59 years at entry, drawn from 12 cohorts from south-western, western, central and eastern Finland. The cohorts consisted of whole or random samples of rural or semiurban dwellers or employees of a factory. The participation rate was 90 per cent. The prevalence of symptoms was determined by the Rose questionnaire and abnormalities on resting ECG were coded according to the Minnesota code. Blood pressure, smoking habits, serum cholesterol, triglycerides, postload plasma glucose and obesity were the risk factors analysed at the baseline examination. The mortality of examinees has been followed continuously. This report deals with the main findings at the baseline examination and the mortality follow-up experience in 5 years. The prevalence of typical angina pectoris was 4.4 per cent in men and 5.4 per cent in women. Unequivocal ECG signs of past myocardial infarction were observed in 1.0 per cent of men and 0.3 per cent of women. Other ECG findings suggesting CHD were observed in 9.2 per cent of men and 11.1 per cent of women. The 5-year mortality was 4.3 per cent in men and 0.9 per cent in women. Men with typical chest pain symptoms had a seven-fold risk to die from CHD, compared to men without symptoms. Men with ECG abnormalities compatible with an old infarction had a 19.5-fold and men with other ECG findings suggesting CHD a 7.1-fold risk to die from CHD compared to men without resting ECG abnormalities. Men with ECG findings as the only indicator of CHD had worse survival than men with symptoms as the only indicator of CHD. The value of symptoms and ECG findings as predictors of CHD mortality in women was very low.

The verbal description of pain is the method most commonly used to study pain symptoms. The Finnish Pain Questionnaire has not been standardized yet. It is impossible to know which descriptors are typical of certain states of pain and which descriptors differentiate states of pain from each other. The aims of this study was to clarify if it is possible to differentiate pain descriptions for coronary heart disease from descriptions for low back pain using the Finnish Pain Questionnaire and to compare the use of pain descriptors and subclasses of descriptors. The patients comprised 57 male patients with coronary heart disease (mean age 52.9 years) and 60 female patients with low back pain (mean age 52.0 years). The results indicated that different descriptors are important in descriptions of coronary heart disease pain and low back pain. The differences of frequencies in the use of descriptors were statistically significant. There were also significant differences in the use of descriptors from different subclasses of the sensory dimension, according to the mechanisms of pain. The results indicated that it is possible to find out which descriptors are the most important for different states of pain and that the Finnish Pain Questionnaire can be a valid method for describing different states of pain.

Ischemic heart disease is more common in East Finland than in West Finland, but systematic comparison and follow-up of incidence figures have not been possible. In 1972 the personal identification number became included in the hospital discharge records, which made it possible to link death certificate data with hospital records from the whole country. The results of this study suggest that high mortality from IHD in some regions is more closely associated with high incidence than a high fatality rate. The proportion of deaths outside hospitals showed large variation by province but this had rather little effect on the total one-year survival rates.

The incidence of myocardial infarction and symptoms of coronary heart disease (CHD) were investigated in a prospective Finnish population study. Drawn from four geographical areas in Finland the study population comprised 5 438 men and 4 924 women aged 30-59 at entry. The results are based on a re-examination of the study population after a mean follow-up time of six years. The average annual incidence of coronary death was 3.8/1 000, and that of non-fatal infarction 6.5/1 000 in men and 0.4/1 000 and 2.1/1 000 in women. Ten per cent of all infarctions were silent, revealed only by ECG changes. Cases of new angina pectoris comprised 40% of all the new events in men but 80% in women. This descriptive report serves as the basis for subsequent analyses comprising risk factors for different CHD manifestations.