The ability of an electrocardiogram to predict fatal and non-fatal cardiac events in asymptomatic middle-aged subjects.

INTRODUCTION: The long-term prognostic value of a standard 12-lead electrocardiogram (ECG) for predicting cardiac events in apparently healthy middle-aged subjects is not well defined. MATERIALS AND METHODS: A total of 9511 middle-aged subjects (mean age 43 ± 8.2 years, 52% males) without a known cardiac disease and with a follow-up 40 years were included in the study. Fatal and non-fatal cardiac events were collected from the national registries. The predictive value of ECG was separately analyzed for 10 and 30 years. Major ECG abnormalities were classified according to the Minnesota code. RESULTS: Subjects with major ECG abnormalities (N = 1131) had an increased risk of cardiac death after 10-years (adjusted hazard ratio [HR] 1.7; 95% confidence interval [95% CI], 1.1-2.5, p = 0.009) and 30-years of follow-up (HR 1.3, 95% CI, 1.1-1.5, p < 0.001). Model discrimination measured with the C-index showed only a minor improvement with the inclusion of ECG abnormalities: 0.851 versus 0.853 and 0.742 versus 0.743 for 10- and 30-year follow-up, respectively. ECG did not predict non-fatal cardiac events after 10-years or 30-years of follow-up. DISCUSSION: Major ECG abnormalities are associated with an increased risk of short and long-term cardiac mortality in middle-aged subjects. However, the improvement in discrimination between subjects with and without fatal cardiac events was marginal with abnormal ECG. KEY MESSAGES: Abnormalities observed on 12-lead electrocardiogram are shown to have prognostic significance for cardiac events in elderly subjects without known cardiac disease. Our results suggest that ECG abnormalities increase the risk of fatal cardiac events also in middle-aged healthy subjects.

Prognostic implications of intraventricular conduction delays in a general population: the Health 2000 Survey.

AIMS: We examined the prognostic impact of eight different intraventricular conduction delays (IVCD) in the standard electrocardiogram (ECG) in a community cohort. METHODS AND RESULTS: Data were collected from 6299 Finnish individuals. During a mean 8.2 years (interquartile range 8.1 to 8.3) of follow-up 640 subjects died (10.2%); 277 (4.4%) were cardiovascular deaths. For both sexes, all-cause and cardiovascular mortality was higher in subjects with IVCD than in those without. In Cox regression analysis after adjustment for age and gender, the hazard ratio for cardiovascular mortality for non-specific IVCD was 4.25 (95% confidence interval [CI] 1.95-9.26, P < 0.0001) and for left bundle branch block (LBBB) 2.11 (95% CI 1.31-3.41, P = 0.002). Right bundle branch block (RBBB) was not related to additional mortality, while incomplete RBBB (IRBBB) presented a hazard ratio of 2.24 (95% CI 1.064-4.77, P = 0.036). CONCLUSIONS: In the general population, non-specific IVCD, LBBB, and IRBBB were associated with increased relative risk for all-cause and cardiovascular mortality. RBBB did not have an impact on cardiovascular mortality either in subjects with or without previous heart disease.

Prevalence and prognostic significance of fragmented QRS complex in middle-aged subjects with and without clinical or electrocardiographic evidence of cardiac disease.

We wanted to evaluate the prevalence and prognostic value of the fragmented QRS (fQRS) complex, defined as changes in QRS morphology with various RSR'-patterns in 12-lead electrocardiogram (ECG) in a middle-aged general population. We evaluated the 12-lead ECGs of 10,904 Finnish middle-aged subjects (52% men, mean age 44 ± 8.5 years) with (n = 2,543) and without (n = 8,361) an evidence of cardiac disease drawn from general population and followed them for 30 ± 11 years. Fragmentation of the QRS complex was defined as various RSR'-patterns in at least 2 consecutive leads within the same territory (inferior II, III, aVF; lateral I, aVL, V4 to V6; anterior V1 to V3). Primary end points were death from any cause, cardiac, and arrhythmic deaths. In the total population, fQRS was present in 19.7% (n = 2,147) of subjects, including 15.7% (n = 1714) in inferior leads, 0.8% (n = 84) in lateral leads, and 2.9% (n = 314) in anterior leads. Fragmentation was not associated with increased mortality in subjects without a known cardiac disease. However, fQRS observed in lateral leads in subjects with an evidence of cardiac disease was associated with an increased risk of all-cause (p = 0.001), cardiac (p = 0.001), and arrhythmic (p = 0.004) mortalities. In conclusion, fQRS reflecting minor intraventricular conduction defect is a common finding, especially in the inferior leads, but it is not a sign of increased risk of mortality in subjects without a known cardiac disease. Lateral fQRS, which is less commonly observed in the ECG, is associated with a worse outcome in patients with a known cardiac disease.

Prognostic significance of prolonged PR interval in the general population.

AIMS: Prolonged PR interval, or first degree AV block, has been traditionally regarded as a benign electrocardiographic finding in healthy individuals, until recent studies have suggested that it may be associated with increased mortality and morbidity. The aim of this study was to further elucidate clinical and prognostic importance of prolonged PR interval in a large middle-aged population with a long follow-up. METHODS AND RESULTS: We evaluated 12-lead electrocardiograms of 10 785 individuals aged 30-59 years (mean age 44 years, 52% males) recorded between 1966 and 1972, and followed the subjects for 30 ± 11 years. Prolonged PR interval was defined as PR >200 ms, with further analysis performed using PR ≥220 ms. Main endpoints were all-cause mortality, cardiovascular mortality, and sudden cardiac death, and other endpoints included hospitalizations due to cardiovascular causes. During the baseline examination, prolonged PR interval >200 ms was present in 2.1% of the subjects, but PR interval normalized to ≤200 ms in 30% of these individuals during the follow-up. No increase in mortality or in hospitalizations due to coronary artery disease, heart failure, atrial fibrillation, or stroke was associated with prolonged PR interval (P = non-significant for all endpoints). These results were not changed after multivariate adjustment or in several subanalyses. CONCLUSION: In the middle-aged general population, prolonged PR interval normalizes in a substantial proportion of subjects during the time course, and it is not associated with an increased risk of all-cause or cardiovascular mortality.

Sagittal abdominal diameter as a new predictor for incident diabetes.

OBJECTIVE: Obesity, particularly visceral adiposity, is a major risk factor for type 2 diabetes. The commonly used obesity indicators, BMI, waist girth, and waist-to-hip ratio (WHR), have limited ability to measure the visceral adipose tissue. Sagittal abdominal diameter (SAD) has been shown to predict the amount of visceral fat. So far no study has been published on its ability to predict diabetes occurrence. RESEARCH DESIGN AND METHODS: We assessed and compared the prediction of the four obesity indicators for diabetes incidence in a prospective study based on 5,168 participants from the nationally representative Health 2000 study. RESULTS: During a mean follow-up lasting 8.1 years, 222 incident diabetes cases occurred. In multivariate models adjusted for lifestyle factors, BMI, waist girth, WHR, and SAD were significant predictors of diabetes incidence. The relative risks (95% CI) between high and low levels were 15.0 (6.94-32.6), 11.4 (5.39-23.8), 12.5 (6.47-24.2), and 14.7 (6.89-31.2), respectively. Pairwise interaction analysis showed that the co-occurrence of high BMI and high SAD was associated with the highest diabetes incidence, with a relative risk of 37.0 (11.2-122). After adjustment for waist girth and the components of the metabolic syndrome, the relative risk was 9.88 (2.81-34.7). The corresponding population-attributable fraction estimate was 84% (49-95). CONCLUSIONS: The combination of SAD and BMI measurements yields a new predictor of diabetes incidence.

Prevalence of ventricular conduction blocks in the resting electrocardiogram in a general population: the Health 2000 Survey.

AIMS: The prevalence of eight different ventricular conduction blocks and their association with risk factors and major cardiovascular diseases were studied in a major Finnish population study. METHODS: Data, including 12-lead electrocardiograms, were collected from 6315 subjects. The prevalence of left bundle branch block (LBBB), right bundle branch block (RBBB), non-specific ventricular block, incomplete LBBB, incomplete RBBB, R-R'-pattern, left anterior hemiblock (LAHB), and left posterior hemiblock (LPHB) was calculated for both genders in three age groups. Their association with risk factors and cardiovascular diseases was studied. RESULTS: R-R'-pattern was the most common ventricular conduction block in all age groups (3.9%, p<0.001 for comparison between groups), but it showed no association with cardiovascular diseases. Males had more RBBB (1.5% vs. 0.7%, p<0.001), incomplete LBBB (1.8 vs. 0.4, p<0.001) and non-specific ventricular block (1.1% vs. 0.1%, p<0.001). With increasing age (<45 years vs. >55 years) LBBB, RBBB and LAHB (0 vs. 2.2%, 0.3 vs. 2.2%, 0.2 vs. 1.9% respectively, p-values<0.001) became more prevalent. LBBB, RBBB and non-specific ventricular conduction block were associated with coronary heart disease (angina pectoris in 28.3, 20.3 and 22.9%, respectively) and heart failure (25.0, 10.1 and 11.4%, respectively). LBBB and RBBB were also associated with peripheral vascular disease (8.8%). CONCLUSIONS: Ventricular conduction blocks differ in prevalence between sexes and age groups. They also show disparate association with cardiovascular diseases. These differences need to be taken into consideration in everyday clinical practice.

Complementary prediction of cardiovascular events by estimated apo- and lipoprotein concentrations in the working age population. The Health 2000 Study.

BACKGROUND: Apolipoprotein A-I (apoA-I) and B (apoB) and multiple lipoprotein cardiovascular risk factors can be computationally estimated with our extended Friedewald approach (EFW) from classical inputs. Their impact on cardiovascular events and mortality in the working age population is not known. METHODS: The working age (≤ 65 years, n = 5956) prospective population-based cohort (follow-up of 7.8 ± 0.9 years; 46,572 patient years, 409 non-fatal incident cardiovascular events, and 55 cardiovascular and 266 all-cause deaths) had their total serum cholesterol (TC), triglycerides (TG), and HDL-C measured. Continuous net reclassification improvement (NRI) was calculated. RESULTS: In Cox models adjusted with cardiovascular risk factors, EFW-HDL(2)-C (HR 0.78, 95% CI 0.67-0.91; NRI 16.5%), apoA-I (HR 0.78, 95% CI 0.69-0.89; NRI 15.2%), apoB/apoA-I (HR 1.23, 95% CI 1.08-1.40; NRI 20.6%), and VLDL-TG (HR 1.15, 95% CI 1.05-1.25; NRI 20.1%) were associated with incident non-fatal cardiovascular events and improved risk prediction compared with TC, LDL-C, or non-HDL-C. Cardiovascular deaths could be best predicted with EFW apoB (HR 1.81, 95% CI 1.18-2.77; NRI 77.3%). CONCLUSIONS: EFW approach-derived HDL(2)-C, apoA-I, apoB/apoA-I, and VLDL-TG improve prediction of non-fatal cardiovascular events, and apoB of cardiovascular mortality, and can be utilized for risk estimation in a working age population without extra cost.

Fatty liver score and 15-year incidence of type 2 diabetes.

PURPOSE: Both non-alcoholic fatty liver (NAFL) and alcoholic fatty liver (AFL) are strongly associated with obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). Recently, also the vitamin D level has been associated with these and may also be associated with fatty liver (FL). Liver function tests (LFTs) are insensitive markers of FL, but use of scores may help in identifying subjects with FL. We studied how LFTs and the FL score predict the development of T2DM in subjects with AFL versus NAFL and low versus high vitamin D levels. METHODS: A cohort study based on 4,517 participants, aged 40-79, from the representative Mini-Finland Health Survey was carried out. During a follow-up of 15 years, 217 T2DM cases occurred. LFTs were determined from serum samples, and the FL score was formed using BMI, fasting glucose, HDL cholesterol, and GGT concentrations. RESULTS: The risk of T2DM incidence in the highest versus lowest quartile was twofold for the LFTs and ninefold for the FL score. A total of 77 % (95 % confidence interval: 57-87 %) of the T2DM cases could have been prevented if all individuals' FL scores had been at the level of the first quartile. Heavy alcohol consumption and low serum vitamin D concentrations were associated with an increased risk of T2DM among individuals with high FL scores. CONCLUSIONS: The FL score is a useful tool for diagnosing FL in epidemiological studies. A high FL score predicts increased risk of T2DM, especially when combined with heavy alcohol consumption or low vitamin D levels.

Polychlorinated biphenyls in prospectively collected serum and Parkinson's disease risk.

Evidence suggests possible Parkinson's disease (PD)-relevant neural effects of exposure to polychlorinated biphenyls. Limited epidemiological evidence suggests that polychlorinated biphenyl exposure may increase PD risk, but no studies have involved biomarkers of polychlorinated biphenyl exposure before PD onset. We examined the prospective association between serum polychlorinated biphenyls and PD. We conducted a nested case-control study within the Finnish Mobile Clinic Health Examination Survey with serum samples collected during 1968-1972 and analyzed in 2005-2007 for polychlorinated biphenyls. Incident PD cases were identified through the Social Insurance Institution's registry and were confirmed by medical record review (n = 101). Controls (n = 349) were matched on age, sex, municipality, and vital status. We used logistic regression to estimate adjusted odds ratios. There was no evidence of increasing risk of PD with increasing polychlorinated biphenyl exposure in adjusted analyses. Instead, there was a trend toward lower odds of PD with increasing serum polychlorinated biphenyl concentrations, which was most pronounced for the sum of all measured polychlorinated biphenyl congeners and the sum of dioxin-like congeners. Compared with that of those in the lowest quintile, the odds ratio of PD among those in the highest quintile of total polychlorinated biphenyls was 0.29 (95% confidence interval, 0.12-0.70; P trend = .02) and for dioxin-like congeners was 0.34 (95% confidence interval, 0.13-0.90; P trend = .05). These results do not support an increased risk of PD from polychlorinated biphenyl exposure and instead suggest a possible protective effect of polychlorinated biphenyl exposure.

Prevalence and prognostic significance of T-wave inversions in right precordial leads of a 12-lead electrocardiogram in the middle-aged subjects.

BACKGROUND: T-wave inversion in right precordial leads V(1) to V(3) is a relatively common finding in a 12-lead ECG of children and adolescents and is infrequently found also in healthy adults. However, this ECG pattern can also be the first presentation of arrhythmogenic right ventricular cardiomyopathy. The prevalence and prognostic significance of T-wave inversions in the middle-aged general population are not well known. METHODS AND RESULTS: We evaluated 12-lead ECGs of 10 899 Finnish middle-aged subjects (52% men, mean age 44 ± 8.5 years) recorded between 1966 and 1972 for the presence of inverted T waves and followed the subjects for 30 ± 11 years. Primary end points were all-cause mortality, cardiac mortality, and arrhythmic death. T-wave inversions in right precordial leads V(1) to V(3) were present in 54 (0.5%) of the subjects. In addition, 76 (0.7%) of the subjects had inverted T waves present only in leads other than V(1) to V(3). Right precordial T-wave inversions did not predict increased mortality (not significant for all end points). However, inverted T waves in leads other than V(1) to V(3) were associated with an increased risk of cardiac and arrhythmic death (P<0.001 for both). CONCLUSIONS: T-wave inversions in right precordial leads are relatively rare in the general population, and are not associated with adverse outcome. Increased mortality risk associated with inverted T waves in other leads may reflect the presence of an underlying structural heart disease.

Carotid artery intima-media thickness and elasticity in relation to glucose tolerance.

The association between diabetes and subclinical atherosclerosis is well established. The effect of non-diabetic glucose intolerance on early atherosclerosis is not as straightforward, and the data regarding sex-related differences in this matter are limited. Therefore, our aim was to investigate these associations in men and women separately. We studied 1,304 Finnish men and women over 45 years of age who participated in the Finnish Health 2000 Survey. Ultrasonically determined carotid artery intima-media thickness and elasticity were used as markers of early atherosclerosis. Glucose tolerance was categorized according to the American Diabetes Association criteria for diabetes mellitus. Age-adjusted means for carotid artery intima-media thickness and elasticity indices were significantly (P < 0.05) associated with glucose tolerance status in both sexes. There was a trend of increasing early atherosclerosis with the worsening of glucose tolerance in men and women. These associations were weakened in both sexes after further adjustments for other cardiovascular risk factors. In women, but not in men, significant (P < 0.05) associations between glucose tolerance status and carotid artery elasticity were seen even after these further adjustments. Diabetes and non-diabetic glucose intolerance are associated with increased early carotid atherosclerosis compared with normal glucose tolerance in both sexes. Our results suggest that women with glucose intolerance may be in greater risk than men.

Adding a low-dose antihypertensive regimen would substantially improve the control of hypertension and reduce cardiovascular morbidity among uncomplicated hypertensive patients.

AIMS: To assess the utilization of antihypertensive drugs among uncomplicated hypertensive patients in Finland between 2000 and 2006 and to calculate the achievable reduction in cardiovascular morbidity, with intensified antihypertensive treatment. METHODS: From the databases of the Social Insurance Institution of Finland, 428,986 treated hypertensives without diabetes or cardiac disease (further named uncomplicated hypertensives) in 2000 and 591,206 in 2006, respectively, were identified. In addition, from the Health 2000 survey representing the whole Finnish adult population, 729 uncomplicated hypertensives were determined to assess their characteristics and control of hypertension. Applying Law's meta-analyses we calculated the reduction of blood pressure (BP) by intensifying the treatment with low-dose antihypertensive regimens for those with a BP ≥140/90 mmHg. RESULTS: The nationwide data suggests a relative overuse of beta-blockers. Combination antihypertensive treatment increased relatively 8%, while at least three drug combinations increased from 19.8% to 21.6% between 2000 and 2006. However, calculated prevalence of controlled BP (<140/90 mmHg) increased only from 30.3% to 33.9%. Addition of one half standard dose or one to two half standard doses for the treatment of the patients with a BP ≥140/90 mmHg would improve the control of hypertension from 33.9% to 47.8% and 67.3%, respectively. The intensified treatment would reduce strokes by 18% and 28%, and ischaemic heart disease events by 13% and 21%, respectively. CONCLUSIONS: Underutilization of preferred drugs and poor control of BP continues. Surprisingly small addition of the number of low-dose antihypertensive regimen is needed in order to substantially improve the control of hypertension and to decrease cardiovascular morbidity among uncomplicated hypertensive patients.

QRS-T angle as a predictor of sudden cardiac death in a middle-aged general population.

AIMS: Spatial QRS-T angle measured from a 12-lead electrocardiogram (ECG) has been shown to predict cardiac mortality. However, there is a paucity of studies on the prognostic significance of frontal QRS-T angle, which is more readily available from the standard 12-lead ECG. The purpose of the present study was to investigate the importance of wide frontal QRS-T angle, QRS-axis, and T-wave axis as cardiac risk predictors in general population. METHODS AND RESULTS: We evaluated the 12-lead ECGs of 10 957 Finnish middle-aged subjects from the general population recorded between 1966 and 1972, and followed them for 30 ± 11 years. QRS-T angle 0 to 90°, QRS-axis -30 to 90°, and T-wave axis 0 to 90° were considered normal. The primary endpoint was death from arrhythmia, and the secondary endpoints were all-cause mortality and non-arrhythmic cardiac mortality. QRS-T angle ≥ 100° was present in 2.0% of the subjects, and it was associated with an increased risk of sudden arrhythmic death [relative risk (RR) 2.26; 95% confidence interval (CI) 1.59-3.21; P< 0.001) and all-cause mortality (RR 1.57; CI 1.34-1.84; P< 0.001), but not with non-arrhythmic cardiac mortality (RR 1.34; CI 0.93-1.92; P= 0.13). The prognostic significance of wide QRS-T angle was mainly due to abnormal T-wave axis, which predicted death from arrhythmia (RR 2.13; CI 1.63-2.79; P< 0.001), all-cause mortality (RR 1.39; 1.24-1.55; P< 0.001), and non-arrhythmic cardiac death (RR 1.87; CI 1.50-2.34; P< 0.001). CONCLUSION: Frontal QRS-T angle ≥ 100° increases the risk of arrhythmic death, this being mainly the result of an altered T-wave axis.

Relation of positive T wave in lead aVR to risk of cardiovascular mortality.

We examined the prevalence and prognostic impact of a positive T wave in lead aVR (aVRT+) on a standard electrocardiogram in the general population. Data were collected from a large nationally representative (random sample) health examination survey conducted in Finland from 2000 through 2001. The survey consisted of 6,354 subjects (2,876 men and 3,478 women) ≥30 years who participated in the field health examination including standard electrocardiographic (ECG) recording at rest. The prevalence of aVRT+ (defined as positive or isoelectric T wave in lead aVR) was 2.2%. During the median follow-up of 98.5 months (interquartile range 96.6 to 99.6), there were 214 (3.5%) cardiovascular (CV) deaths. In Cox regression analysis after adjustment for age and gender, relative risks for CV and total mortalities associated with aVRT+ were 3.24 (95% confidence interval [CI] 2.32 to 4.54, p <0.001) and 1.91 (95% CI 1.47 to 2.49, p <0.001), respectively. In the fully adjusted model controlling for other risk factors, CV morbidity, and ECG findings, the relative risk for CV mortality for aVRT+ was 2.94 (95% CI 2.07 to 4.18, p <0.001). In conclusion, aVRT+, an easily recognized ECG finding, predicts risk for CV mortality in the general population. This finding could aid in screening for risk of total and CV mortalities.

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.

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.

Prognosis of ischaemic stroke is improving similarly in patients with type 2 diabetes as in nondiabetic patients in Finland.

BACKGROUND: Case fatality of first ischaemic stroke has improved markedly during the past two decades. Aims To investigate whether stroke patients with type 2 diabetes have shared this favourable development. METHODS: Nation-wide registers were used to identify all patients with type 2 diabetes in Finland during 1988-2002. All first ischaemic strokes among them and also among all nondiabetic persons were identified from the National Hospital Discharge Register and the Causes of Death Register. Trends over time were calculated, for age-standardised case fatality of first stroke events, separately for two time periods: 0-27 and 28-364 days after the onset of stroke. These trends were compared between patients with type 2 diabetes and nondiabetic patients. RESULTS: Altogether, 23,097 first-ever ischaemic strokes were recorded among 222,940 persons with type 2 diabetes. The 28 day case fatality was 1.1-1.3 times higher, and the one-year case fatality of 28 day survivors was 1.4-2.2 times higher in patients with type 2 diabetes compared with nondiabetic patients. A significant decline in case fatality trends was observed, but the trends did not differ between type 2 diabetes and nondiabetic patients. CONCLUSIONS: The study revealed a positive development in survival after the first stroke event in persons with type 2 diabetes, similar to the development in nondiabetic persons. However, the level of case fatality has remained higher in patients with type 2 diabetes.

Optimal schedule for home blood pressure measurement based on prognostic data: the Finn-Home Study.

Current guidelines based on cross-sectional statistical parameters derived from reference populations make equivocal recommendations for the optimal schedule of home blood pressure (BP) measurement. The objective of this study was to determine a schedule for home BP measurements in relation to their predictive value for total cardiovascular risk. Home BP was measured twice every morning and evening for 1 week in an unselected nationwide population of 2081 subjects aged 45 to 74 years. The prognostic significance of BP for fatal and nonfatal cardiovascular events was examined using adjusted Cox proportional hazards regression models. A total of 162 cardiovascular events were recorded during a 6.8-year follow-up. The predictive value of home BP increased progressively with the number of measurements, showing the highest predictive value with the average of all measurements (systolic/diastolic hazard ratio per 1-mm Hg increase in BP: 1.021/1.034; systolic/ diastolic 95% CI: 1.012 to 1.030/1.018 to 1.049). However, most of this increase was achieved during the first 3 days of measurement (hazard ratio: 1.017/1.028; 95% CI: 1.009 to 1.026/1.013 to 1.045), and only minimal increase occurred after day 6. No additional benefit was achieved by discarding the values obtained during the first day of measurement. Morning and evening BPs were equally predictive of future cardiovascular events. Novel prognostic data from this study show that measurement of home BP twice in the morning and evening, preferably for a period of 7 days, or for at least 3 days, provides a thorough image of a patient's BP level. This information should be used to prepare a unified international guideline for home BP measurement.

Aging reduces the functionality of anti-pneumococcal antibodies and the killing of Streptococcus pneumoniae by neutrophil phagocytosis.

We evaluated the effect of aging on the functional activity of naturally acquired anti-pneumococcal antibodies, the function of neutrophils in phagocytic killing of opsonized pneumococci, and the complement activity. Opsonic activities of antibodies to all tested pneumococcal serotypes were significantly lower and phagocytic killing of pneumococci by neutrophils was significantly impaired among the elderly, whereas the complement activity was slightly higher in the elderly than in the young adults. The reduced functional activity of serotype-specific antibodies and the compromised function of neutrophils in the opsonophagocytosis of pneumococci are likely to contribute to the increased susceptibility of the elderly to pneumococcal diseases.

Dietary intervention in infancy and later signs of beta-cell autoimmunity.

BACKGROUND: Early exposure to complex dietary proteins may increase the risk of beta-cell autoimmunity and type 1 diabetes in children with genetic susceptibility. We tested the hypothesis that supplementing breast milk with highly hydrolyzed milk formula would decrease the cumulative incidence of diabetes-associated autoantibodies in such children. METHODS: In this double-blind, randomized trial, we assigned 230 infants with HLA-conferred susceptibility to type 1 diabetes and at least one family member with type 1 diabetes to receive either a casein hydrolysate formula or a conventional, cow's-milk-based formula (control) whenever breast milk was not available during the first 6 to 8 months of life. Autoantibodies to insulin, glutamic acid decarboxylase (GAD), the insulinoma-associated 2 molecule (IA-2), and zinc transporter 8 were analyzed with the use of radiobinding assays, and islet-cell antibodies were analyzed with the use of immunofluorescence, during a median observation period of 10 years (mean, 7.5). The children were monitored for incident type 1 diabetes until they were 10 years of age. RESULTS: The unadjusted hazard ratio for positivity for one or more autoantibodies in the casein hydrolysate group, as compared with the control group, was 0.54 (95% confidence interval [CI], 0.29 to 0.95), and the hazard ratio adjusted for an observed difference in the duration of exposure to the study formula was 0.51 (95% CI, 0.28 to 0.91). The unadjusted hazard ratio for positivity for two or more autoantibodies was 0.52 (95% CI, 0.21 to 1.17), and the adjusted hazard ratio was 0.47 (95% CI, 0.19 to 1.07). The rate of reported adverse events was similar in the two groups. CONCLUSIONS: Dietary intervention during infancy appears to have a long-lasting effect on markers of beta-cell autoimmunity--markers that may reflect an autoimmune process leading to type 1 diabetes. (ClinicalTrials.gov number, NCT00570102.).