This study shows that the effect of traditional risk factors in middle‐aged men change over prolonged follow‐up periods and when re‐measured at old age. Furthermore, the study also points out that ECG changes, such as ST segment depression and T wave abnormalities, are also important risk factors for stroke.
Consistent with another population‐based study carried out in Swedish men aged 47–55 years in 1970–3,15
high blood pressure, smoking and diabetes mellitus were associated with future stroke in middle‐aged men, whereas high cholesterol levels were not. In our cohort, atrial fibrillation, a well‐known risk factor for stroke,15,16
was found to be of importance only in elderly people, probably owing to low prevalence in mid‐life subjects (n
7). SBP was an important risk factor for any‐cause stroke and for ischaemic stroke over three decades of follow‐up when measured at age 50 years. Although being of major importance during the first decades of follow‐up when evaluated at age 50 years, ST segment depression, T wave abnormalities and ECG‐LVH regained significance when re‐measured at age 70 years. Despite lower prevalence, ECG abnormalities had greater impact on risk at age 50 years than at age 70 years. In elderly people only, LDL‐cholesterol was an independent risk factor for future stroke, whereas apoA1 seemed to protect against future stroke.
The strength of our study is that the subjects have been followed for >30 years with repeated investigations. An obvious limitation of our study is the lack of women. There was no validation of the individual stroke cases. However, in previous studies, stroke, defined by combining data from the Cause of Death Registry and Hospital Discharge Registry in Sweden, has been shown to be an efficient, validated alternative to revised hospital discharge notes and death certificates.17
The association between risk factors and any‐cause stroke will be substantially influenced by ischaemic stroke, the dominant stroke subtype in our study population, so it was not surprising that the same results were obtained whether any‐cause stroke cases were analysed or when only those with ischaemic stroke were used in the models. The only main difference was a more pronounced impact of glucose and insulin when only ischaemic stroke cases were considered.
Differences in risk factor patterns for stroke between studies may depend on discrepancies in classification of stroke, dominant stroke subtype in the study population and different follow‐up time or differences in baseline age.18
Since stroke usually occurs later in life than CHD some of the participants in the cohort studies will have died from CHD before reaching the age when stroke occurs, thereby reducing the impact of some traditional cardiovascular risk factors on future development of stroke. This could explain why risk factors such as smoking, diabetes mellitus and high body mass index (BMI) were significant predictors in mid‐life but not at the age of 70 years. Consistent with other studies,19,20,21,22
we found smoking to be associated with stroke, but only in middle‐aged men. This finding could be explained not only by premature death but also by a decrease in smoking with age. The data should not be interpreted that smoking is not a risk factor in old age. Diabetes mellitus was associated with stroke in middle‐aged men only; however, considering the similar point estimates and overlapping confidence intervals it is not possible to exclude the significance in elderly people. Similarly, as found in another study,23
BMI in middle‐aged men was associated with stroke.
The roles of serum cholesterol and lipoprotein fractions as risk factors for stroke are far less consistent and more controversial18,19,24,25,26
than those for myocardial infarction. The Prospective Studies Collaboration, involving >45 prospective observational cohorts and 450
000 individuals, was not able to demonstrate an association between stroke and cholesterol levels even though they recognise that the lack of an overall relationship might conceal a positive association with ischaemic stroke together with a negative association with haemorrhagic stroke.25
Also, analysis of the EUROSTROKE Project could not disclose an association of total cholesterol with fatal, non‐fatal, haemorrhagic or ischaemic stroke26
even though, in men, an increase in HDL‐cholesterol was associated with a non‐significant reduced risk of stroke in all centres. In our study, none of the lipid variables were associated with stroke in mid‐life. However, LDL‐cholesterol was an independent predictor in multivariate analysis in elderly people. Also, in our study, the apoB/apoA1 ratio, with apoA1 driving the significance of the ratio, was found to be a significant predictor for stroke in elderly people. Recent studies have shown that the apoB/apoA1 ratio, which indicates the balance between atherogenic apoB‐containing particles and atheroprotective apoA1‐containing particles, may be a better predictor for CVD than the more traditional markers for dyslipidaemia.27,28,29,30
Qureshi et al31
were unable to demonstrate any statistically significant association between either apoA1 or apoB and stroke.31
However, their baseline investigations were performed at a younger age. A case–control study carried out in a Chinese population found that apoA1 decreased the risk of stroke. In that study, 57% of the patients were older than 70 years,32
further supporting our finding of an important protective role of apoA1 in elderly people. Our study also supports the recent findings by Walldius et al,28
where the apoB/apoA1 ratio was shown to be associated with stroke.
ST segment depression and T wave abnormalities were seen both in LVH and myocardial ischaemia.33
In a study with up to 14 years of follow‐up, in apparently healthy individuals with essential hypertension, LVH diagnosed by ECG or echocardiography was shown to confer an excess risk for stroke and TIA, independently of other individual risk factors.34
The association been ECG‐LVH and stroke in the EUROSTROKE project has been found to be more pronounced in smokers.35
However, it needs to be emphasised that the causal inter‐relationship between ECG‐LVH and specific stroke types is complex and different mechanisms may be involved.
The EUROSTROKE Project, even though the results indicated that ECG‐LVH was a predictor for stroke,35
did not consider ECG characteristics necessary in screening for stroke in the general population, since ECG abnormalities did not contribute to the prediction of stroke according to their model of risk scores.36
Our findings suggest that a standard resting ECG could play an important role in identifying patients at increased risk for stroke and that even minor ECG abnormalities may be of importance when assessing the individual patient's global burden of risk. ECG abnormalities together with low apoA1 levels could help identify elderly patients at increased risk for stroke and thereby contribute to reduction of suffering and disability if effective preventive measures are instituted.
In conclusion, mid‐life values for blood pressure and ECG abnormalities retain their predictive value over long follow‐up periods, even though they improved in predictive power when re‐measured in elderly people. Despite lower prevalence, ECG abnormalities had greater impact at age 50 years than at age 70 years. By contrast, there was evidence that ApoA1 may protect from future stroke in elderly people.
What this paper adds
- During a follow‐up period of over 30 years, systolic blood pressure retained its predictive value for stroke.
- ECG ischaemic abnormalities were of importance only during the first 20 years, but regained importance when re‐measured at age 70 years.
- In the elderly people only, apolipoprotein A1 protected against future stroke.
- Our findings suggest that a standard resting ECG could play an important role in assessing the patients' global burden of risk for stroke.
- ECG abnormalities, together with low apolipoprotein A1 levels, could help to identify elderly patients at increased risk for stroke.