By the end of 41 years of the study, 4,387 persons (64% of the cohort) had died and 1,140 of these (26%) were examined by autopsy at the Gade Institute. The ratio of autopsies to the number of deaths decreased from 40% in the period 1964–1975 to 11% in the period 1995–2005. The autopsy ratio for the upper quartile of age at death (i.e. 84–103 years) fell from 25 to 4%. In participants dying from stroke (according to mortality statistics), the autopsy ratio decreased from 41 to 4%, whereas in those dying from coronary heart disease it decreased from 38 to 14%.
Of the 1,140 subjects examined by autopsy at the Gade Institute in Bergen only 742 (65%) of the autopsy-reports were forwarded and/or recorded in the mortality statistics (Fig. ).
Mortality and autopsy data for the 6,811 survey participants
Of the specific causes of death recorded in mortality statistics, 3,389 (77%) were not based on autopsy findings. The 256 cases of death recorded at Statistics Norway as having been examined by autopsy, but with no autopsy record at the Gade Institute, were evenly distributed over the entire period of the study (“Appendix
” , Fig. ). Until 1996 Statistics Norway recorded that the registered cause of death was based on an autopsy if the physician issuing the Death Certificate had indicated that an autopsy had been planned, but in many of these instances a post mortem examination never took place. The 398 individuals with autopsy records available at the Gade Institute, but with cause of death “not based on autopsy” in the mortality statistics died mainly in the period before 1987 when physicians ordering the post mortem examination were still responsible for forwarding the results of the autopsy to Statistics Norway. From 1987 the pathology departments were responsible for forwarding the autopsy reports and from 1996 Statistics Norway implemented systematic procedures to adjust the registered cause of death according to the findings of the autopsy (“Appendix
”, Fig. ).
Fig. 2 Autopsy-based causes of death recorded in mortality statistics and the respective availability of autopsy data at the Gade Institute. [“lightgrey” (N = 256 cases) denotes autopsies recorded in the mortality statistics, (more ...)
Fig. 3 Causes of death recorded without autopsy in mortality statistics and the respective availability of autopsy data at the Gade Institute. [“darkgrey” (N = 398 cases) denotes autopsies at the Gade Institute, which were not (more ...)
Validity of the diagnosis of fatal strokes in Norwegian mortality statistics
The validity of the diagnosis of fatal stroke in the mortality statistics was assessed by comparing the mortality statistics for which diagnosis had been based on autopsy results with those for which it had not (Table ). The prevalence of fatal strokes in the mortality statistics was the same in the two groups (34/398 = 8.5 vs. 64/742 = 8.6%).
Validity of fatal strokes (Eurocode 36) recorded in Norwegian mortality statistics for 1,140 post mortem examinations, according to whether the autopsy results were available or not
Of the 28 under-diagnosed (false negative) fatal strokes in the mortality statistics, the registered causes of death were diseases of the circulatory system (Eurocode 33) in 12 cases (including ischemic heart disease (Eurocode 34) in 9 cases), pneumonia (Eurocode 39) in 5 cases, malignant neoplasm (Eurocode 07) in 4 cases and other Eurocodes in 7 cases.
Of the 13 over-diagnosed (false positive) fatal strokes reported in the mortality statistics, the autopsy had identified diseases of the circulatory system in 9 cases (including ischemic heart disease in 5 cases), diseases of the lungs/airways in 2 cases, malignant neoplasm in 1 case and 1 other case.
For fatal strokes the kappa coefficient indicated “substantial” agreement irrespective of whether autopsy results were available to inform the mortality statistics or not (Table ). The positive predictive value of fatal stroke in mortality statistics was slightly improved when autopsy results were available, but the change of sensitivity was not statistically significant (based on the overlapping of confidence intervals).
The kappa coefficients calculated for the 4 different quartiles of the follow-up period (before 1978, 1978–1986, 1987–1995, 1996–2005) were 0.83, 0.77, 0.70, and 0.85 respectively, showing no trend of increasing diagnostic validity over time.
As hypertension is the most established risk factor for cerebral stroke, we tested whether hypertension had predicted fatal stroke according to the mortality statistics differently from fatal stroke according to the autopsy records. We used Cox proportional hazard regression, adjusted for age at the baseline examination (when the blood pressure was measured) and for gender. With fatal stroke from mortality statistics as the outcome the hazard ratio was 1.71, 95% CI [1.4, 2.08] and as the outcome from autopsy records the hazard ratio was 1.70, 95% CI [1.07, 2.68].
Validity of the diagnosis of coronary deaths in Norwegian mortality statistics
As for stroke, the recorded coronary deaths in the mortality statistics were divided into subgroups according to whether the diagnoses were based on autopsy results or not, and the validity of the mortality statistics was assessed (Table ). The prevalence of coronary deaths in the mortality statistics was 79/399 (20%) in the subgroup where autopsy results had been reported as unavailable, whereas it was 253/742 (34%) in the subgroup where autopsy results had been reported as available.
Validity of coronary deaths (Eurocode 34) recorded in Norwegian mortality statistics for 1,140 post mortem examinations, according to whether the autopsy results were available or not
Of the 40 under-diagnosed (false negative) coronary deaths in the mortality statistics, the registered causes of death were diseases of the circulatory system (Eurocode 33) in 20 cases (of which stroke (Eurocode 36) in 5 cases), respiratory diseases (Eurocode 37) in 7 cases, malignant neoplasm (Eurocode 07) in 7 cases and others in 6 cases. Of the 48 over-diagnosed (false positive) coronary death reports in the mortality statistics, the autopsy reports concluded on diseases of the circulatory system in 20 cases (of which stroke in 9 cases), diseases of the lungs/airways in 11 cases and malignant neoplasm in 2 cases, and others in 15 cases.
For coronary deaths the kappa coefficient increased from “substantial” to “almost perfect” agreement when the autopsy results were available to the mortality statistics. The sensitivity of ischemic heart disease in the mortality statistics was slightly improved when the autopsy results were available, but for the positive predictive value the difference was not statistically significant (based on the overlapping confidence intervals).
In the 4 quartiles of the study period the combined kappa coefficients were 0.81, 0.79, 0.81, and 0.83, respectively.
With coronary death (Eurocode 34) from the mortality statistics as the outcome the Cox proportional hazard ratio associated with hypertension was 1.58, 95% CI [1.38, 1.82]. With coronary death verified from the autopsy record as the outcome the hazard ratio was 1.52 95% CI [1.17, 1.99], both adjusted for age at baseline and gender.
Predictors of post mortem examination and the association to fatal stroke
The selection of deaths for autopsy in a general population is not random. We tested the following potential predictors for effect upon the odds of undergoing post mortem examination: age at death (quartiles), period of death (before 1987 vs. 1987 or later), gender, and cause of death (cerebral stroke or coronary disease). The independent variables were explored in bivariate and multivariate analyses. Bivariate logistic regression included only the predictor of interest and the outcome (autopsy). Multivariate logistic regression included gender, age at death and period of death. Cause of death was compared to all other deaths (Table ).
Predictors of autopsy for 4,387 subjects who died during follow-up
As can be seen from Table , death from cerebral stroke was a negative predictor of referral for autopsy, whereas death from coronary heart disease was not, both adjusted for gender, period of death and age at death. Female gender was also a negative predictor of autopsy. There was no statistically significant interaction between the categorical variables included in these analyses.