Childhood oral infections linked to subclinical carotid atherosclerosis in adulthood
Association of Childhood Oral Infections With Cardiovascular Risk Factors and Subclinical Atherosclerosis in AdulthoodLiterature - Pussinen PJ, Paju S, Koponen J et al. - JAMA Netw Open. 2019;2(4):e192523. doi:10.1001/jamanetworkopen.2019.2523
Introduction and methods
Oral infections (periodontal diseases and dental caries) are common infection-induced inflammatory diseases that start early in life [1-3]. If untreated, the conditions may progress to more severe periodontal and endodontal infections, which may ultimately result in tooth loss.
Periodontitis is now recognized as an independent risk factor for atherosclerotic CV diseases, but the evidence does not support causality . Oral dysbiosis and local inflammation contribute to systemic inflammatory burden by releasing inflammatory mediators and bacterial stimuli into the circulation . Periodontal treatment reverses endothelial dysfunction and reduces inflammatory and lipid biomarkers, thereby improving the atherosclerotic profile .
Exposure to CV risk factors early in life has been associated with the development of atherosclerosis in adulthood . No long-term studies have been performed to study the role of childhood oral infections in CV risk. This study therefore investigated the association of childhood oral infections with preclinical carotid atherosclerosis after 27 years of follow-up. The number of signs of oral infections in childhood in relation to CV risk factor profiles during follow-up were assessed. Cumulative exposure to CV risk factors was assessed during 5 appointments. The number of teeth (both deciduous and permanent) were recorded, and present or previous (treated) dental infections (caries and fillings) and periodontal disease (gingival bleeding on probing and periodontal probing pocket depths) were measured.
755 Participants from the ongoing Cardiovascular Risk in Young Finns Study  were included, who underwent a baseline evaluation (including dental) in 1980 at age 6, 9, or 12 years, and a clinical CV follow-up in adulthood in 2001 at age 27, 30 or 33 years, and/or in 2007 at age 33, 36 or 39 years. In 2001 (n=468) and 2007 (n=489), intima media thickness (IMT) was measured on the posterior wall of the left carotid artery.
- 33 Children (4.5%) had no sign of oral infections, 41 (5.6%) had 1 sign, 127 (17.4%) had 2 signs, 278 (38.3%) had 3 signs, 248 (34.1%) had 4 signs. Most children (91.2%) reported to brush their teeth daily, but 12.2% of boys and 5.6% of girls did not.
- Those with 4 signs of oral infections showed a higher systolic BP (8.1 [2,4] mmHg, P-0.001) and diastolic BP (6.5 [1.9] mmHg, P=0.001) than those without signs of oral infections.
- In adulthood, the mean number of CV risk factors increased with the number of signs of oral infections (P-linear trend: 0.04) and during the whole follow-up (mean [SE] number of CV risk factors for no sign of oral infections: 11.4 [0.9], up to 14.1 [0.9] for 4 signs, P-trend: 0.01). This increasing trend was particularly clear in childhood, with 5.31 [0.6] for no sign, up to 7.2 [0.2] with 4 signs (P-trend: 0.008).
- In the IMT measurements in 2001 and 2007, the lowest values were seen in those without signs of oral infections. The mean [SD] difference in IMT between those with no sign and those with 4 signs was 0.056 [0.019] mm (P=0.004) in 2001 and 0.051 [0.017] mm (P=0.003 in 2007.
- A linear regression model adjusted for the cumulative exposure to CV risk factors suggested that caries and fillings (β=0.145), bleeding and pocketing (β=0.135) and number of signs of oral infections (β=0.158) were significantly associated with IMT in 2007.
- Presence of any sign of oral infection in childhood was associated with increased IMT in 2007 (highest tertile vs. lowest two, RR: 1.87, 95%CI: 1.25-2.79). Presence of all 4 signs yielded an RR of 1.95, 95%CI: 1.28-3.00.
- In multivariate analyses, boys with 4 signs of oral infections showed a higher risk of high IMT 27 years later (RR: 2.25, 95%CI: 1.30-3.89) than girls (RR: 1.51, 95%CI: 0.80-2.85).
This analysis of the Cardiovascular Risk in Young Finns Study found that oral infections in childhood are linked to the development of subclinical carotid atherosclerosis 27 years later. Participants with signs of oral infection, including bleeding on probing, increased probing pocket depth, caries or fillings, showed an almost two-fold risk for increased IMT in early middle age. Oral infections were an independent risk factor for increased IMT, after adjustment for cumulative exposure to CV risk factors. Thus, these data suggest that oral infections in childhood may represent a modifiable risk factor for adult CV disease.
Merchant and Virani  consider three possible explanations for the association found by Pussinen and colleagues. First, individuals with poor oral health as children, also have poor oral health when they are adults. In adults, several lines of evidence support the hypothesis that poor oral health leads to atherosclerosis. Microorganisms associated with periodontal disease have been detected in atherosclerotic lesions. No clinical trial has tested the hypothesis that periodontal treatment has a beneficial effect on CVD, possibly because periodontal disease is not cured, but rather controlled or contained by regular dental treatment, which involves repeated follow-up visits.
The second possible explanation of the findings is that poor oral health is not causally related to CVD. Poor oral and CV health share common risk factors. Pussinen et al. effectively controlled for the average effect of potential confounders during follow-up by means of the area under the curve method. Thus, Merchant and Virani consider unmeasured confounding an unlikely explanation for these results.
The last explanation they consider, is that the positive association is a consequence of selection bias secondary to loss of follow-up. For this scenario to be the explanation in the current study, those with poor oral health in childhood and no atherosclerosis as adults would need to selectively drop out, or those with good oral health as children and atherosclerosis in adulthood. This is unlikely in the current study, because measured atherosclerosis was subclinical. Plus, the investigators aimed to correct for selection bias with inverse probability weighting.
The question of causality remains unanswered, and is unlikely to be addressed in a conventional randomized clinical trial due to the nature of the intervention to treat periodontal disease. Nevertheless, Merchant and Virani think that this article ‘underscores the idea that the distinction between oral health and systemic health is blurred and somewhat artificial. Cardiovascular disease and periodontal disease share common risk factors, and controlling those risk factors could result in better overall health.’