Harri Rissanen

Long-term outcome associated with early repolarization on electrocardiography

BACKGROUND Early repolarization, which is characterized by an elevation of the QRS-ST junction (J point) in leads other than V(1) through V(3) on 12-lead electrocardiography, has been associated with vulnerability to ventricular fibrillation, but little is known about the prognostic significance of this pattern in the general population. METHODS We assessed the prevalence and prognostic significance of early repolarization on 12-lead electrocardiography in a community-based general population of 10,864 middle-aged subjects (mean [+/-SD] age, 44+/-8 years). The primary end point was death from cardiac causes, and secondary end points were death from any cause and death from arrhythmia during a mean follow-up of 30+/-11 years. Early repolarization was stratified according to the degree of J-point elevation (> or = 0.1 mV or > 0.2 mV) in either inferior or lateral leads. RESULTS The early-repolarization pattern of 0.1 mV or more was present in 630 subjects (5.8%): 384 (3.5%) in inferior leads and 262 (2.4%) in lateral leads, with elevations in both leads in 16 subjects (0.1%). J-point elevation of at least 0.1 mV in inferior leads was associated with an increased risk of death from cardiac causes (adjusted relative risk, 1.28; 95% confidence interval [CI], 1.04 to 1.59; P=0.03); 36 subjects (0.3%) with J-point elevation of more than 0.2 mV in inferior leads had a markedly elevated risk of death from cardiac causes (adjusted relative risk, 2.98; 95% CI, 1.85 to 4.92; P<0.001) and from arrhythmia (adjusted relative risk, 2.92; 95% CI, 1.45 to 5.89; P=0.01). Other electrocardiographic risk markers, such as a prolonged QT interval corrected for heart rate (P=0.03) and left ventricular hypertrophy (P=0.004), were weaker predictors of the primary end point. CONCLUSIONS An early-repolarization pattern in the inferior leads of a standard electrocardiogram is associated with an increased risk of death from cardiac causes in middle-aged subjects.

Early Repolarization Electrocardiographic Phenotypes Associated With Favorable Long-Term Outcome

Background— Early repolarization (ER) in inferior/lateral leads of standard ECGs increases the risk of arrhythmic death. We tested the hypothesis that variations in the ST-segment characteristics after the ER waveforms may have prognostic importance. Methods and Results— ST segments after ER were classified as horizontal/descending or rapidly ascending/upsloping on the basis of observations from 2 independent samples of young healthy athletes from Finland (n=62) and the United States (n=503), where ascending type was the dominant and common form of ER. Early repolarization was present in 27/62 (44%) of the Finnish athletes and 151/503 (30%) of the US athletes, and all but 1 of the Finnish (96%) and 91/107 (85%) of US athletes had an ascending/upsloping ST variant after ER. Subsequently, ECGs from a general population of 10 864 middle-aged subjects were analyzed to assess the prognostic modulation of ER-associated risk by ST-segment variations. Subjects with ER ≥0.1 mV and horizontal/descending ST variant (n=412) had an increased hazard ratio of arrhythmic death (relative risk 1.43; 95% confidence interval 1.05 to 1.94). When modeled for higher amplitude ER (>0.2 mV) in inferior leads and horizontal/descending ST-segment variant, the hazard ratio of arrhythmic death increased to 3.14 (95% confidence interval 1.56 to 6.30). However, in subjects with ascending ST variant, the relative risk for arrhythmic death was not increased (0.89; 95% confidence interval 0.52 to 1.55). Conclusions— ST-segment morphology variants associated with ER separates subjects with and without an increased risk of arrhythmic death in middle-aged subjects. Rapidly ascending ST segments after the J-point, the dominant ST pattern in healthy athletes, seems to be a benign variant of ER.Background— Early repolarization (ER) in inferior/lateral leads of standard ECGs increases the risk of arrhythmic death. We tested the hypothesis that variations in the ST-segment characteristics after the ER waveforms may have prognostic importance. Methods and Results— ST segments after ER were classified as horizontal/descending or rapidly ascending/upsloping on the basis of observations from 2 independent samples of young healthy athletes from Finland (n=62) and the United States (n=503), where ascending type was the dominant and common form of ER. Early repolarization was present in 27/62 (44%) of the Finnish athletes and 151/503 (30%) of the US athletes, and all but 1 of the Finnish (96%) and 91/107 (85%) of US athletes had an ascending/upsloping ST variant after ER. Subsequently, ECGs from a general population of 10 864 middle-aged subjects were analyzed to assess the prognostic modulation of ER-associated risk by ST-segment variations. Subjects with ER ≥0.1 mV and horizontal/descending ST variant (n=412) had an increased hazard ratio of arrhythmic death (relative risk 1.43; 95% confidence interval 1.05 to 1.94). When modeled for higher amplitude ER (>0.2 mV) in inferior leads and horizontal/descending ST-segment variant, the hazard ratio of arrhythmic death increased to 3.14 (95% confidence interval 1.56 to 6.30). However, in subjects with ascending ST variant, the relative risk for arrhythmic death was not increased (0.89; 95% confidence interval 0.52 to 1.55). Conclusions— ST-segment morphology variants associated with ER separates subjects with and without an increased risk of arrhythmic death in middle-aged subjects. Rapidly ascending ST segments after the J-point, the dominant ST pattern in healthy athletes, seems to be a benign variant of ER. # Clinical Perspective {#article-title-24}

Serum vitamin D and subsequent occurrence of type 2 diabetes.

Background: Low vitamin D status has been suggested as a risk factor for type 2 diabetes. Although the epidemiologic evidence is scarce, 2 recent studies have suggested an association. The present study investigated the relation of serum vitamin D with type 2 diabetes incidence using pooled data from these 2 cohorts. Methods: Two nested case-control studies, collected by the Finnish Mobile Clinic in 1973–1980, were pooled for analysis. The study populations consisted of men and women aged 40–74 years and free of diabetes at baseline. During a follow-up period of 22 years, 412 incident type 2 diabetes cases occurred, and 986 controls were selected by individual matching. Serum vitamin D (serum 25(OH)D) was determined from frozen samples, stored at baseline. Pooled estimates of the relationship between serum vitamin D concentration and type 2 diabetes incidence were calculated. Results: Men had higher serum vitamin D concentrations than women and showed a reduced risk of type 2 diabetes in their highest vitamin D quartile. The relative odds between the highest and lowest quartiles was 0.28 (95% confidence interval = 0.10–0.81) in men and 1.14 (0.60–2.17) in women after adjustment for smoking, body mass index, physical activity, and education. Conclusions: The results support the hypothesis that high vitamin D status provides protection against type 2 diabetes. Residual confounding may contribute to this association.

Vitamin D Status and the Risk of Cardiovascular Disease Death

Accumulating evidence suggests that inadequate vitamin D levels may predispose people to chronic diseases. The authors aimed to investigate whether serum 25-hydroxyvitamin D (25(OH)D) level predicts mortality from cardiovascular disease (CVD). The study was based on the Mini-Finland Health Survey and included 6,219 men and women aged > or =30 years who were free from CVD at baseline (1978-1980). During follow-up through 2006, 640 coronary disease deaths and 293 cerebrovascular disease deaths were identified. Levels of 25(OH)D were determined from serum collected at baseline. Coxs proportional hazards model was used to assess the association between 25(OH)D and risk of CVD death. After adjustment for potential confounders, the hazard ratio for total CVD death was 0.76 (95% confidence interval (95% CI): 0.60, 0.95) for the highest quintile of 25(OH)D level versus the lowest. The association was evident for cerebrovascular death (hazard ratio = 0.48, 95% CI: 0.31, 0.75) but not coronary death (hazard ratio = 0.91, 95% CI: 0.70, 1.18). A low vitamin D level may be associated with higher risk of a fatal CVD event, particularly cerebrovascular death. These findings need to be replicated in other populations. To demonstrate a causal link between vitamin D and CVD, randomized controlled trials are required.

Prevalence and Prognostic Significance of Short QT Interval in a Middle-Aged Finnish Population

Background— Short-QT syndrome is an inherited disorder characterized by a short QT interval and an increased risk of sudden cardiac death. The clinical significance of a short QT interval observed in a randomly recorded ECG is not known. Therefore, we assessed the prevalence and prognostic significance of a short QT interval in a general population. Methods and Results— QT intervals were measured from the 12-lead ECGs of 10 822 randomly selected middle-aged subjects (5658 males, mean age 44±8.4 years) enrolled in a population study and followed up for 29±10 years. The end points were all-cause and cardiovascular mortality. In addition to Bazett’s method (corrected QT interval, or QTc), the Fridericia (QTfc) and nomogram (QTnc) methods were used to correct the QT interval for heart rate. The cutoff values for short QT intervals were defined as 320 ms (very short) and 340 ms (short). The prevalence of QT interval <320 ms based on QTc, QTfc, and QTnc was 0.10%, 0.08%, and 0.06%, and the prevalence of QT interval <340 ms was 0.4%, 0.3%, and 0.3%, respectively. The majority of subjects with short QT intervals were males. All-cause or cardiovascular mortality did not differ between subjects with a very short or short QT interval and those with normal QT intervals (360 to 450 ms). There were no sudden cardiac deaths, aborted sudden cardiac deaths, or documented ventricular tachyarrhythmias among subjects with a QTfc <340 ms. Conclusion— A short QT interval does not appear to indicate an increased risk for all-cause or cardiovascular mortality in middle-aged nonreferral, community-based individuals.

Antibodies to periodontal pathogens and stroke risk.

Background and Purpose— The association between cerebrovascular events and periodontitis has been found in few studies based on clinical periodontal examinations. However, evidence on the association between periodontal pathogens and stroke is lacking. Therefore, the aim of the study was to investigate whether elevated levels of serum antibodies to major periodontal pathogens predict stroke in a case–control study. Methods— The study population comprised 6950 subjects (aged 45 to 64 years) who participated in the Mobile Clinic Health Survey in 1973 to 1976 in Finland. During a follow-up of 13 years, a total of 173 subjects had a stroke. From these, 64 subjects had already experienced a stroke or had signs of coronary heart disease (CHD) at baseline, whereas 109 subjects were apparently healthy. Two controls per case were matched for age, gender, municipality, and disease status. Serum IgG and IgA class antibody levels to the periodontal pathogens, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis, were determined by multiserotype enzyme-linked immunosorbent assay. Results— The cases identified during the follow-up that were free of stroke or CHD at baseline were more often IgA-seropositive for A. actinomycetemcomitans than were their controls, 41.3% versus 29.3%. Compared with the seronegative, the seropositive subjects had a multivariate odds ratio of 1.6 (95% CI, 1.0 to 2.6) for stroke. The patients with a history of stroke or CHD at baseline were more often IgA-seropositive for P. gingivalis than were their controls, 79.7% versus 70.2%. When compared with the seronegative, the seropositive subjects had an odds ratio of 2.6 (1.0 to 7.0) for secondary stroke. Conclusions— The present prospective study provides serological evidence that an infection caused by major periodontal pathogens is associated with future stroke.

Quercetin intake and the incidence of cerebrovascular disease

Objective: To study the relation between intake of the antioxidant flavonoid quercetin and subsequent incidence of cerebrovascular disease (CVA).Design: A cohort study carried out among 9208 Finnish men and women 15 y or more of age and initially free from cardiovascular disease. During a 28 y follow-up period in 1967–1994, a total of 824 cases with CVA were diagnosed.Methods: Food consumption data were collected using a dietary history interview method covering the total habitual diet during the previous year.Results: Quercetin intake was not associated with CVA incidence. The relative risk of CVA adjusted for age, serum cholesterol, body mass index, smoking, hypertension, diabetes, geographical area, occupation and intake of beta-carotene, vitamin E, vitamin C, fibre, various fatty acids, and energy between the highest and lowest quartiles of quercetin intake was 0.99 (95% confidence interval (CI)=0.71–1.38) for men and 0.85 (CI=0.60–1.21) for women. In contrast, apples, the major source of quercetin in the study population, showed a significant inverse association both in men and women, mainly due to an association with thrombotic or embolic stroke. The relative risks of thrombotic stroke after further adjustment for quercetin intake were 0.59 (CI=0.35–0.99; P=0.45) and 0.61 (CI=0.33–1.12: P for trend=0.02) for men and women, respectively.Conclusions: The results suggest that the intake of apples is related to a decreased risk of thrombotic stroke. This association apparently is not due to the presence of the antioxidant flavonoid quercetin.European Journal of Clinical Nutrition (2000) 54, 415–417

Prospective study of coffee consumption and risk of Parkinson's disease

Objective:To examine the prediction of coffee consumption on the incidence of Parkinsons disease.Subjects and methods:The study population comprised 6710 men and women, aged 50–79 years and free from Parkinsons disease at the baseline. At baseline, enquiries were made about coffee consumption in a self-administered questionnaire as the average number of cups per day. During a 22-year follow-up, 101 incident cases of Parkinsons disease occurred. Parkinsons disease cases were identified through a nationwide registry of patients receiving medication reimbursement, which is based on certificates from neurologist.Results:After adjustments for age, sex, marital status, education, community density, alcohol consumption, leisure-time physical activity, smoking, body mass index, hypertension and serum cholesterol, the relative risk for subjects drinking 10 or more cups of coffee per day compared with non-drinkers was 0.26 (95% confidence interval 0.07–0.99, P-value for trend=0.18). The association was stronger among overweight persons and among persons with lower serum cholesterol level (P-value for interaction=0.04 and 0.03, respectively).Conclusions:The results support the hypothesis that coffee consumption reduces the risk of Parkinsons disease, but protective effect of coffee may vary by exposure to other factors.

Intraventricular Conduction Delay in a Standard 12-Lead Electrocardiogram as a Predictor of Mortality in the General Population

Background— Prolonged duration of QRS complex in a 12-lead ECG is associated with adverse prognosis in patients with cardiac disease, but its significance is not well established in the general population. In particular, there is a paucity of data on the prognostic significance of nonspecific intraventricular conduction delay in apparently healthy subjects. Methods and Results— We evaluated the 12-lead ECGs of 10 899 Finnish middle-aged subjects from the general population (52% of whom were men; mean age 44±8.5 years) between 1966 and 1972 and followed them for 30±11 years. Primary end points were all-cause mortality, cardiac mortality, and arrhythmic death. Prolonged QRS duration was defined as QRS ≥110 ms and intraventricular conduction delay as QRS ≥110 ms, without the criteria of complete or incomplete bundle-branch block. QRS duration ≥110 ms was present in 1.3% (n=147) and intraventricular conduction delay in 0.6% (n=67) of the subjects. Prolonged QRS duration predicted all-cause mortality (multivariate-adjusted relative risk [RR] 1.48; 95% confidence interval [CI] 1.22–1.81; P<0.001), cardiac mortality (RR 1.94; CI 1.44–2.63; P<0.001), and sudden arrhythmic death (RR 2.14; CI 1.38–3.33; P=0.002). Subjects with intraventricular conduction delay had increased all-cause mortality (RR 2.01; CI 1.52–2.66; P<0.001), increased cardiac mortality (RR 2.53; CI 1.64–3.90; P<0.001), and an elevated risk of arrhythmic death (RR 3.11; CI 1.74–5.54; P=0.001). Left bundle-branch block also weakly predicted arrhythmic death (P=0.04), but right bundle-branch block was not associated with increased mortality. Conclusions— Prolonged QRS duration in a standard 12-lead ECG is associated with increased mortality in a general population, with intraventricular conduction delay being most strongly associated with an increased risk of arrhythmic death.

Vitamin D Status and the Risk of Lung Cancer: A Cohort Study in Finland

Experimental data support the suppressing effect of vitamin D on lung carcinogenesis, but epidemiologic evidence is limited. The aim of the present study was to evaluate whether serum 25-hydroxyvitamin D [25(OH)D] level is associated with the risk of lung cancer in a prospective cohort study in Finland. 25(OH)D levels were measured by RIA from serum collected at baseline (1978-1980) from 6,937 men and women. During a maximum follow-up of 24 years, 122 lung cancers were identified. After adjustment for potential confounders, no overall significant association between vitamin D and lung cancer risk was observed [relative risk (RR) for the highest versus lowest tertile, 0.72; 95% confidence interval (95% CI), 0.43-1.19; Ptrend = 0.22]. There was a statistically significant interaction between vitamin D and sex (P = 0.02) and age (P = 0.02): serum 25(OH)D level was inversely associated with lung cancer incidence for women (RR, 0.16; 95% CI, 0.04-0.59; Ptrend < 0.001) and younger participants (RR, 0.34; 95% CI, 0.13-0.90; Ptrend = 0.04) but not for men (RR, 1.03; 95% CI, 0.59-1.82; Ptrend = 0.81) or older individuals (RR, 0.92; 95% CI, 0.50-1.70; Ptrend = 0.79). In conclusion, although there was no overall association between vitamin D and lung cancer risk, women and young participants with a higher level of vitamin D were observed to have a lower lung cancer risk. Although experimental data support the suppressing effect of vitamin D on the development of lung cancer, large epidemiologic studies from different populations with repeated measurements of vitamin D are warranted to confirm this finding. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3274–8)