Young adults with periodontitis at higher risk for cryptogenic ischemic stroke

Periodontitis, a common condition, has been linked to a specific type of ischemic stroke in a recent study published in the Journal of Dental Research.

​​​​​​​Study: Periodontitis, Dental Procedures, and Young-Onset Cryptogenic Stroke. Image Credit: Olga by Shefer/​​​​​​​Study: Periodontitis, Dental Procedures, and Young-Onset Cryptogenic Stroke. Image Credit: Olga by Shefer/


Strokes are the second leading cause of death worldwide. Over the past few decades, the incidence of ischemic strokes has increased among younger populations, resulting in a higher prevalence in this age group.

Risk factors for stroke include inactive lifestyles, smoking, obesity, hypertension, and diabetes, all of which are related to lifestyle and potentially modifiable. Additionally, a large Taiwanese study has suggested that periodontitis may also increase the risk of ischemic stroke, particularly among younger individuals.

Many more strokes among the young are of unknown origin and are called cryptogenic ischemic strokes (CIS), accounting for the largest proportion of young-onset strokes among people without vascular risk factors.

Oral health and strokes

Bacteria involved in periodontitis release factors like lipopolysaccharides (LPS) and lipotechoic acid (LTA). These are toxins from Gram-negative and Gram-positive bacteria cell membranes, respectively.

Endotoxemia refers to the passage of LPS into the bloodstream, mostly from the gut, with a lesser role played by the oral mucosa and inflamed gums. The part played by endotoxemia and ischemic stroke is still unclear.

Dental procedures cause bacteria to enter the circulation, at least temporarily, and promote clotting. The inflammatory response to such procedures might increase the odds of strokes, heart attacks, or other acute cardiovascular events. Their association with ischemic stroke remains to be proven, however.

The current study explored associations between CIS and periodontitis or dental surgery in younger adults.

About the study

The participants were drawn from multiple centers included in the SECRETO study, with a case-control design. All participants were between 18 and 49 years of age.

Each case was confirmed to have a cryptogenic ischemic stroke (CIS) by imaging. They had no CIS history. The cases were matched for age and sex with controls who did not present with stroke.

The researchers adjusted for confounding factors such as stroke risk, regular dental care, and a patent foramen ovale (PFO) in the heart. PFA is associated with a higher risk of cerebral bacteremia and stroke.

What did the study show?

The total number of participants comprised 146 paired cases and controls, with a median age of ~42 years. Cases were less educated, more likely to have hypertension and to drink heavily compared to controls.

They also had a higher prevalence of PFO than controls, were more likely to be on statins or anti-coagulant drugs, and had used antibiotics in the recent past.

Oral health and CIS

The CIS cases had poorer oral health. Periodontal inflammation (denoted by the Periodontal Inflammation Burden Index (PIBI) and gum pocket depth) was higher, and there was greater bleeding on probing (BOP). 

About 28% of the stroke cases had periodontitis vs 20% of controls. CIS cases had the most severe stage of periodontitis (Stage IV) vs controls who did not go beyond stage III. All grades of periodontitis were seen among controls, but only more severe grades (B and C) in CIS patients.

Not only was periodontitis associated with moderate to severe CIS cases vs mild CIS, but the odds of more severe periodontitis were almost fourfold higher among those with moderate-to-severe CIS.  

CIS odds increased more than tenfold with a high PIBI. Among those with severe periodontitis, the odds were 7.5-fold higher.  

Moreover, stroke severity also soared with the severity of periodontitis. Moderate to severe CIS risk was increased by fivefold among those with a PIBI over 10. The odds of severe stroke were more than sixfold higher among those with severe periodontitis.

Dental treatments and CIS

Over 90% of dental treatments in CIS cases occurred within four months before the stroke. These patients had extractions, endodontic treatments, dental fillings, and chronic tooth infections at higher rates than in controls.

When there was a history of invasive dental treatments within the three months preceding the stroke, the risk of CIS was more than doubled. The odds were sixfold higher among individuals with PFO.

The titers of LPS or LTA did not show any difference between the two groups but did increase with the severity of periodontitis.


This is the largest study examining the link between young CIS and oral health. Both moderate to severe periodontitis, with a fast-progressing profile, as well as a history of recent invasive dental surgery were risk factors for young-onset CIS.

The risk is dose-dependent, with CIS being more common as the severity of periodontitis increases. Stroke severity also increased with more severe periodontitis.

The findings corroborate a previous study and show an independent increase in CIS risk with periodontal disease independent of other risk factors like obesity, PFO, smoking, heavy drinking, and educational status.

Earlier studies suggested associations with bacteremia, which remain unconfirmed in this study. The results indicate that invasive dental treatments may have a benefit after six months, though the short-term risk of CIS is increased. This remains to be investigated in future studies.

Journal reference:
Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.


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