Leif Sourander

Prediction of sudden cardiac death by fractal analysis of heart rate variability in elderly subjects.

OBJECTIVES The aim of this study was to test the hypothesis that abnormal scaling characteristics of heart rate (HR) predict sudden cardiac death in a random population of elderly subjects. BACKGROUND An abnormality in the short-term fractal scaling properties of HR has been observed to be related to a risk of life-threatening arrhythmias among patients with advanced heart diseases. The predictive power of altered short-term scaling properties of HR in general populations is unknown. METHODS A random sample of 325 subjects, age 65 years or older, who had a comprehensive risk profiling from clinical evaluation, laboratory tests and 24-h Holter recordings were followed up for 10 years. Heart rate dynamics, including conventional and fractal scaling measures of HR variability, were analyzed. RESULTS At 10 years of follow-up, 164 subjects had died. Seventy-one subjects had died of a cardiac cause, and 29 deaths were defined as sudden cardiac deaths. By univariate analysis, a reduced short-term fractal scaling exponent predicted the occurrence of cardiac death (relative risk [RR] 2.5, 95% confidence interval [CI], 1.9 to 3.2, p < 0.001) and provided even stronger prediction of sudden cardiac death (RR 4.1, 95% CI, 2.5 to 6.6, p < 0.001). After adjusting for other predictive variables in a multivariate analysis, reduced exponent value remained as an independent predictor of sudden cardiac death (RR 4.3, 95% CI, 2.0 to 9.2, p < 0.001). CONCLUSIONS Altered short-term fractal scaling properties of HR indicate an increased risk for cardiac mortality, particularly sudden cardiac death, in the random population of elderly subjects.

Cardiovascular and cancer morbidity and mortality and sudden cardiac death in postmenopausal women on oestrogen replacement therapy (ERT)

BACKGROUND Advantages and disadvantages of postmenopausal oestrogen replacement therapy (ERT) are still not clear. We aimed to analyse the relation between postmenopausal oestrogen replacement therapy (ERT), cardiovascular disease, and cancer. METHODS We examined 7944 women born between 1923 and 1930, who participated in a mammography screening for breast cancer, and who were followed up from 1987 to 1995. The follow-up consisted of 53,305 person-years. 988 women were current users and 757 were former users of ERT. Information about hormone use and health events was obtained through biennial questionnaires and recording and linking information from the hospital discharge registers of the region, the national cancer register, the social insurance reimbursement register, and the national death register. We used proportional-hazards models to calculate risk ratios and 95% CIs, adjusted for eight confounding variables. FINDINGS Current ERT was associated with decreased cardiovascular mortality and a decrease in sudden cardiac death. Adjusted risk ratio (RR) for cardiovascular mortality in current users was 0.21 (95% CI 0.08-0.59) and in former users 0.75 (0.41-1.37). Absolute risk per 1000 person-years for deaths from acute myocardial infarction (AMI) was 1.1 in never users, 1.2 in former users, and 0.45 in current users (p=0.197). Corresponding absolute risk for other coronary-artery-disease (CAD) deaths was 1.0, 0.81, and 0 (p=0.009), and for deaths from stroke 1.2, 1.0, and 0.15 (p=0.012). Absolute risk for sudden cardiac death was 1.6 in never users, 1.0 in former users, and 0 in current users (p<0.001). Cardiovascular morbidity was not decreased by ERT: the RR for current use was 1.07 (0.86-1.32) and for former use 1.11 (0.89-1.39). Incidence of cardiovascular disease per 1000 person-years was 24.9 in never users, 23.4 in former users, and 20.9 in current users (p=0.153). Breast-cancer morbidity did not increase with current ERT--the RR was 0.57 (0.27-1.20). Incidence of breast cancer was 1.8, 1.6, and 1.0 in never, former, and current users (p=0.242). Endometrial cancer increased with current ERT--the RR was 5.06 (2.47-10.41). Incidence of endometrial cancer was 0.52 in never users, 0.51 in former users, and 2.1 in current users (p<0.001). INTERPRETATION Current ERT reduced primarily sudden cardiac death and predicted reduced cardiovascular mortality, but did not reduce morbidity. ERT did not increase the risk of breast cancer, but was associated with increased risk of endometrial cancer.

Alzheimer's disease in Finnish twins

BACKGROUND The genetics of Alzheimers disease (AD) are obscure. Although most cases are sporadic half the patients with sporadic AD have a positive family history. The mode of genetic transmission and the role of environmental factors are unknown. The purpose of this study was to examine the contribution of genetic factors to the pathogenesis of AD in a twin cohort. METHODS The Finnish Twin Cohort consists of all Finnish same-sexed twin pairs born before 1958 with both co-twins alive in 1975. The total number of twin pairs is 13 888, of whom 4307 are monozygotic (MZ) and 9581 ar dizygotic (DZ). These data were linked with the Hospital Discharge Register from 1972 to 1991 to identify twins who had dementia or related disease as a discharge diagnosis. The linkage of the registries yielded a total of 285 twin individuals. The medical records of these twins and their co-twins were reviewed to confirm and classify dementia (AD, vascular dementia, mixed dementia, and other dementia). The incidence, concordance, and age at onset of AD were examined. FINDINGS The incidence of AD was significantly higher in MZ than in DZ twin individuals, with and adjusted MZ/DZ incidence ratio of 1.8 (95% confidence intervals 1.2 to 2.7). In contrast, the incidence of vascular or mixed dementia did not differ between MZ and DZ individuals (MZ/DZ ratio 0.6 [0.3 to 1.2]) for vascular and 1.0 [0.5 to 2.1] for mixed dementia). The pairwise concordance for AD was 18.6% in MZ pairs and 4.7% in DZ pairs and the corresponding probandwise concordance rates were 31.3% and 9.3%. The pairwise concordance for vascular dementia was 18.2% in MZ pairs and 6.7% in DZ pairs with corresponding probandwise rates of 30.8% and 12.5%. The onset age of AD concordant MZ pairs was identical in two pairs and diverged by up to 15 years. INTERPRETATION The higher incidence of AD in MZ individuals than in DZ individuals may provide a clue to the aetiology of AD. The higher concordance rate of MZ pairs confirms the contribution of the major genetic component while indicating the need to identify environmental triggers.

Clinical features of leuko-araiosis.

OBJECTIVE: To study the clinical features of leuko-araiosis. METHODS: Age matched groups of patients with a CT finding of pure leukoaraiosis (n = 26) and a control group with a normal CT finding (n = 26) were formed (mean ages 78.6 (SD 3.3) v 76.5 (SD 4.6) years; NS). RESULTS: Dementia, vascular dementia, central brain atrophy on CT, disability in activities of daily living and instrumental activities of daily living, urinary incontinence, gait disorder (assistance needed), personality change, and night time confusion were found to be more commonly present in leuko-araiosis positive patients than in controls, whereas focal neurological symptoms and signs were not associated with leuko-araiosis. The occurrences of heart failure and systolic hypotension-but not hypertension-were higher in the leuko-araiosis positive group than in the controls. Leuko-araiosis was also found to be related to a less sudden onset of symptoms and a lower Hachinski score than true brain infarction(s). CONCLUSIONS: Leuko-araiosis on CT in these elderly patients seems to be a vascular disorder aetiologically different from brain infarction, with clinical manifestations of subtle onset and general disabling nature and no prominent focal neurological signs or symptoms.

Prevalence and characteristics of symptomatic gastroesophageal reflux disease in the elderly.

Objective: To study prevalence and characteristics of symptomatic gastroesophageal reflux disease in the elderly.

Clinical Presentation of Peptic Ulcer in the Elderly

The aim of this study was to determine the age-related characteristics of peptic-ulcer patients. A total of 125 consecutive patients (63 men and 62 women) with peptic ulcer were studied prospectively. The ulcers were diagnosed at endoscopy. The mean age of patients was 62 years (57 years in men and 68 in women). Patients were asked about their use of nonsteroidal anti-inflammatory drugs (NSAIDs). The main symptom, the duration of symptoms, the ulcer location and size, and the presence of Helicobacter pylori (HP) from the histologic specimen were recorded. Ulcer complications such as bleeding or perforation were also noted. These parameters were compared in two age groups: 65 years or under (n = 65) and over 65 years (n = 60). In the older age group, duodenal ulcer was less common (42 vs. 66%, p = 0.008) and typical epigastric pain was rare (35 vs. 91%, p < 0.001). Ulcer bleeding was present more commonly in the older age group (50 vs. 14%, p < 0.001). The duration of symptoms was shortest in patients who used NSAIDs, especially among older patients. Elderly patients also had an atypical location more often (39 vs. 15%, p = 0.003). After adjustment for use of NSAIDs, these characteristics remained among the elderly. The presence of HP was less common in the older age group (56 vs. 92%, p < 0.001). Furthermore, in the group of elderly patients who did not use NSAIDs, 35% were HP-negative. In conclusion, the presentation of peptic ulcer in the elderly has distinct characteristics, which are not entirely related to the use of NSAIDs.

Environmental differences in twin pairs discordant for Alzheimer’s disease

The aim of this study was to examine the contribution of environmental factors to the pathogenesis of Alzheimer’s disease by comparing environmental differences in twin pairs discordant for Alzheimer’s disease. Seventy four twin pairs discordant for Alzheimer’s disease were found by linking the Finnish twin cohort and the Hospital Discharge Register from years 1972–91. In 50 pairs (25 monozygotic and 25 dizygotic pairs), both co-twins had responded to a questionnaire survey in 1975. Exposure differences were compared between these pairs. A reduced risk of Alzheimer’s disease was significantly associated with a higher level of schooling (relative risk 0.3; 95% confidence interval 0.1–0.9, p=0.029). In addition, a reduced risk was suggestively associated with ambidextrousness or left handedness (p=0.083) and an increased risk with marriage (p=0.052), widowhood (p=0.074), and a history of cholelithiasis (p=0.071). In conclusion, a reduced risk of Alzheimer’s disease was associated with a higher level of schooling.

Alzheimer's disease in twins

Besides familial Alzheimers disease (AD), the genetic susceptibility has also been found in sporadic cases of AD, mostly related to the apolipoprotein E polymorphism. The penetrance of AD is determined by age and probably by environmental exposure. Gene-environment interaction of a disease can be examined through studies of twins. The relative roles of genetic and environmental influences can be estimated by comparing the concordance rates between monozygotic (MZ) and dizygotic (DZ) twins. Genetic models can be used to specify contributions both from genetic as well as shared and unique environmental effects. The role of environmental factors can be investigated in the co-twin control study, either by comparing environmental exposure in MZ twins discordant for a disease or by comparing MZ twins discordant for an exposure suspected of causing a particular disease. The sampling of twin pairs AD can be carried out using voluntary recruitment, linkage of twin and hospital discharge registries or screening of twin registry population. Potential sources of biases in sampling are discussed. The majority of the published twin studies on AD are case reports or based on selected materials. In MZ pairs, the concordance rates for AD have varied between 31% and 83%. Only one co-twin control study in twins discordant for AD has been published. Published twin studies on AD are briefly reviewed.

A marked increase in the incidence of colorectal cancer over two decades in southwest Finland

The Finnish Cancer Registrys data on all colorectal cancer cases from 1971 to 1990 in southwest Finland, an area of mean population of 433,000, were analyzed. The age-adjusted incidence of colon cancer per 100,000 population increased in men from 8.5 in 1971-1980 to 13.5 in 1981-1990 and in women from 10.3 to 13.1. The incidence of male rectal cancer increased from 9.8 to 11.1 and in women from 6.4 to 7.1. The proportion of elderly patients clearly rose and, in 1981-1990, patients over 65 years of age had 68.4% of all colon cancers and 73.9% of all rectal cancers. There was a proximal shift in the site distribution of cancers: the proportion of rectal cancers decreased from 45.9% in 1971-1980 to 40.9% in 1981-1990. This change was most marked in men. There was no change in the spread and operability of colorectal cancers during the two decades. There was an increase in colon cancer mortality while the mortality of rectal cancer cancer slightly decreased.

Leukoaraiosis and cause of death: a five year follow up.

The causes of death of 127 patients, who had undergone CT examination of the brain in 1989, were investigated. The CT was re-evaluated. Twenty five patients were excluded because of pathological findings on CT other than leukoaraiosis (LA), infarction, or their combination or, because of a specific known aetiology for LA. Of the remaining 102 patients, 25 had pure LA, 18 had pure infarction, 37 had LA combined with infarction (cLA), and 22 had a normal CT. The mean time between the CT and death was 1.8 (SD 1.5) years. A vascular cause of death was clearly associated with LA and with the severity of LA. Patients with pure LA had a vascular cause of death as often as those with pure infarction and those with LA combined with infarction. These groups differed significantly from each other when comparing the occurrence of cerebrovascular, cardiovascular and other vascular causes of death. The results suggest that LA on CT is more likely to be associated with a cardiovascular cause of death, and pure infarction is more often associated with a cerebrovascular death.