Author's response to reviews Title: Number of teeth and myocardial infarction and stroke among elderly never smokers Authors:

Background: In most previous studies the association between number of teeth and cardiovascular diseases has been found to be stronger among younger age groups than in older age groups, which indicates that age may modify the association between number of teeth and cardiovascular diseases. We investigated the association between tooth loss and atherosclerotic vascular diseases such as myocardial infarction and stroke in a homogeneous elderly population. The study population was comprised of a subpopulation of 392 community-living elderly people who participated in the population-based Kuopio 75+ study. The data were collected through an interview, a structured clinical health examination and from patient records. The main outcome measures were a history of diagnosed myocardial infarction and diagnosed ischemic stroke. Prevalence proportion ratios (PPR) were estimated using generalised linear models. Results: Edentate subjects had a weakly, statistically non-significantly increased likelihood of a history of myocardial infarction and ischemic stroke compared with dentate subjects. Those with a large number of teeth had a slightly, but not statistically significantly increased likelihood of a history of myocardial infarction and ischemic stroke compared with those with a small number of teeth. Conclusion: These data did not show evidence that total or partial tooth loss would be associated with atherosclerotic vascular diseases such as myocardial infarction and ischemic stroke among an elderly population aged 75 years or older. Background Cardiovascular diseases (CVD) are one of the main causes of death in the world, accounting for almost one third of all deaths world-wide [1] and about half of all deaths in Europe [2]. Cardiovascular diseases consist of heterogeneous groups of vascular diseases, with atherosclerotic vascular diseases being the commonest group. Although the risk factors of atherosclerotic vascular diseases include several risk factors such as abnormal lipids, hypertension, smoking and diabetes [3], a substantial proportion of cardiovascular events cannot be attributed to any of the risk factors [4]. During the past three decades, oral epidemiologists have been actively testing the hypothesis that oral infections may be aetiological factors in atherosclerotic vascular diseases. Different explanatory variables such as periodontal pocket depth, clinical attachment loss or different indices have been used to measure the extent and/or severity of oral infection. Tooth loss, measured by number of teeth, has also been used as an explanatory variable, especially in situations where no other form of data is available. In earlier studies, tooth loss has been associated with atherosclerotic diseases such as myocardial infarction (MI) [5-6], coronary heart disease [7-8] and stroke [9-10]. In addition, total tooth loss, edentulism, has been associated with fatal coronary heart disease [11], stroke/transient ischemic attack [12], stroke [13] and nonhemorrhagic stroke as well as all cerebrovascular accidents [14]. On the other hand, other studies have failed to show any association between number of teeth and myocardial infarction [15-16], myocardial infarction or angina pectoris or unstable angina [17] or coronary heart disease [18]. The association between tooth loss and cardiovascular diseases has been suggested to be due to different reasons, such as previous periodontal infections, caries, bacteraemia related to extractions, change in diet followed by tooth loss and biases such as selection bias, information bias and confounding related to attitudinal, behavioural and biological factors in common [19]. Most previous studies involve heterogeneous study populations that include both middle-aged and elderly persons; typically the mean age is under 70 years. Studies that have investigated the association in different age groups have shown that the association between number of teeth and cardiovascular diseases is stronger among younger age groups than in older age groups [9,20], which indicates that age may modify the association between number of teeth and cardiovascular diseases. Our aim was to study whether there is an association between number of teeth and atherosclerotic diseases such as myocardial infarction and ischemic stroke among a homogenous study population aged 75 years or older. Results The descriptive statistics of the study population are shown in Tables 1 and 2. After controlling for gender, age, basic education, diabetes, hypertension, smoking, alcohol consumption, physical activity, body mass index (BMI), serum triglycerides and serum high-density lipoprotein (HDL) cholesterol, dentate persons have a slightly, non-significantly decreased likelihood of having a history of myocardial infarction (PPR 0.9 95% CI: 0.5–1.8) or ischemic stroke (PPR 0.9 95% CI: 0.2–2.8) when compared with edentulous subjects. Number of teeth was weakly and statistically non-significantly associated with a history of myocardial infarction (PPR 1.01 95% CI: 0.97–1.05) and ischemic stroke (PPR 1.02 95% CI: 0.94–1.08) (Table 3). The joint effect of dentulous/ edentulous and number of teeth is presented in figures 1 and 2. It can be seen that the joint effect of these variables forms a J-shaped curve. From the figures it can be seen that the likelihood of a history of both MI and stroke is lowest among those with a small number of teeth. The equivalent point when compared with edentulous subjects was 5 teeth for MI and 8 teeth for stroke. Due to unequal gender distribution, interactions between gender and explanatory variables were tested. The p-values for interaction terms between gender and number of teeth was 0.89 and between gender and dentate vs. edentate, 0.87, for myocardial infarction. For stroke, the corresponding values were 0.26 and 0.57.