Women with high-risk strains of human papillomavirus (HPV) had a far higher risk of death from certain types of cardiovascular disease (CVD), a prospective cohort study from Korea found.
Compared to women without high-risk strains, those with high-risk HPV had more than a threefold higher risk of death from both atherosclerotic CVD (ASCVD; HR 3.91, 95% CI 1.85-8.26) and ischemic heart disease (HR 3.74, 95% CI 1.53-9.14), reported Yoosoo Chang, MD, PhD, of Kangbuk Samsung Hospital in Seoul, South Korea, and colleagues.
And as they described in the , the higher death risk due to ASCVD among women with high-risk HPV was even greater when overweight or obesity was also a factor (P=0.006 for interaction):
- With overweight or obesity: HR 4.81 (95% CI 1.55-14.93)
- Without overweight or obesity: HR 2.86 (95% CI 1.04-7.88)
"HPV is predominantly known for its role in causing cervical and other cancers, so uncovering its significant impact on cardiovascular mortality opens new avenues for understanding the systemic effects of this virus," co-author Hae Suk Cheong, MD, PhD, also of Kangbuk Samsung Hospital, told in an email.
"This knowledge is crucial for healthcare providers, as it underscores the importance of considering high-risk HPV status in the overall cardiovascular risk assessment of patients," said Cheong.
In their analysis, the researchers adjusted for CVD risk factors and other potential confounders, with models showing similar results when also accounting for triglycerides, LDL and HDL cholesterol, homeostatic model assessment for insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein.
"These findings, when added to other evidence linking HPV and other viruses to higher CVD mortality, make a strong case for accepting viruses as risk factors for adverse outcomes from ASCVD," wrote James Lawson, MD, of the University of New South Wales in Sydney, and colleagues in an .
There are two mechanisms that could explain how HPV infections might contribute to CVD, according to the editorialists: "First, viruses could directly invade atherosclerotic plaques, thereby causing plaque progression and/or instability. Second, they could trigger a systemic inflammatory response and produce acute prothrombotic changes by activating platelets or the blood coagulability."
"The evidence that viruses in general and HPV in particular increase the risk of adverse outcomes from ASCVD has become compelling enough to add to the already strong case for vaccination against influenza virus, SARS-CoV-2, and HPV," commented Lawson and co-authors.
The study from Chang and colleagues included 163,250 Korean women ages 30 and up (mean 40 years) who were tested for high-risk HPV. Of these, 9% had high-risk HPV. Women were excluded from the study if they had a history of CVD, malignancy, or a hysterectomy. Participants underwent a variety of health screening tests, including cervical screening for 13 high-risk strains of HPV.
They returned for health checks every 1 to 2 years. At baseline, women had a low prevalence of conventional CVD risk factors, such as smoking, diabetes, hypertension, and use of lipid-lowering therapies. Researchers combined data on HPV test results with nationwide records on deaths from CVD.
In total, 134 CVD deaths occurred over a median follow-up of 8.6 years, with some women tracked for as long as 17 years. The authors noted that the absolute mortality rate was low in this relatively young population of women with few CVD risk factors, with mortality rates of 14.9 and 9.1 per 100,000 person-years for the women with and without high-risk HPV, respectively.
The main analysis adjusted for age, sex, education, smoking status, alcohol consumption, exercise, BMI, use of medication for hyperlipidaemia, and a history of diabetes or hypertension, among other factors.
Overall, the researchers found a higher risk of CVD death in women with high-risk HPV (HR 1.68, 95% CI 1.04-2.72), but no significant association between high-risk HPV and mortality from ischemic stroke (HR 5.86, 95% CI 0.86-40.11) or other forms of CVD when ASCVD was excluded (HR 1.07, 95% CI 0.55-2.06).
Two important limitations of the study were that it did not include data on HPV vaccination status or specific HPV genotypes in vaccinated women.
Disclosures
The study was funded by the Sungkyunkwan University Excellence in Research Award Research Fund.
Study authors and editorialists disclosed no relationships with industry.
Primary Source
European Heart Journal
Cheong HS, et al "Human papillomavirus infection and cardiovascular mortality: a cohort study" Eur Heart J 2024; DOI: 10.1093/eurheartj/ehae020.
Secondary Source
European Heart Journal
Chan NC, et al "Human papilloma virus and atherosclerotic cardiovascular disease" Eur Heart J 2024; DOI: 10.1093/eurheartj/ehad829.