In the JournalsPerspective

HPV increases risk for CVD

Women with high-risk HPV had an increased risk for CVD, especially in those with metabolic syndrome and obesity, according to a study published in Circulation Research.

“A better understanding of high-risk HPV as a risk factor for cardiovascular disease and possible combined effects of high-risk HPV, obesity and metabolic syndrome in increasing cardiovascular disease risk may help improve preventive strategies and patient outcomes,” Seungho Ryu, MD, PhD, professor at Kangbuk Samsung Hospital at Sungkyunkwan University School of Medicine in Seoul, South Korea, said in a press release.

Eun-Jeong Joo, MD, PhD, of the division of infectious diseases at Kangbuk Samsung Hospital at Sungkyunkwan University School of Medicine, and colleagues analyzed data from 63,411 women (mean age, 40 years; mean BMI, 22 kg/m2) without CVD at baseline from the Kangbuk Samsung Health Study.

Women completed questionnaires to collect information on demographics, alcohol consumption, smoking status, education level, physical activity, family history of CVD and medical history of CVD or cancer. Physical examinations were also performed to measure BP, height and weight, in addition to collect blood samples and conduct high-risk HPV tests.

The primary outcome of interest was incident CVD, defined as the first diagnosis for CVD including stroke, ischemic heart disease and transient ischemic attack. Follow-up was conducted for 261,598.9 person-years and a median duration of 4.4 years.

Of the women in the study, 7.6% had high-risk HPV. During follow-up, 1,122 cases of new-onset CVD were diagnosed with an incidence rate of 4.3 per 103 person-years.

After adjusting for age, the HR for women who were high-risk HPV-positive vs. those who were high-risk HPV negative was 1.26 (95% CI, 1.03-1.53). A significant relationship between HPV and CVD persisted after adjusting for possible confounders and high-sensitivity C-reactive protein (HR = 1.25; 95% CI, 1.03-1.52). This association was stronger in women with obesity (P for interaction = .02) and metabolic syndrome (P for interaction = .05).

Women with high-risk HPV and without obesity had an increased risk for incident CVD vs. those without high-risk HPV (HR = 1.1; 95% CI, 0.87-1.39). The risk then increased in women with high-risk HPV and obesity (HR = 1.73; 95% CI, 1.19-2.51). Similar results were seen in women without metabolic syndrome (HR = 1.09; 95% CI, 0.87-1.36) and those with metabolic syndrome (HR = 1.99; 95% CI, 1.28-3.08).

“This suggests that high-risk HPV might affect CVD risk when accompanied by obesity or [metabolic syndrome],” Joo and colleagues wrote. “Further studies are required to identify the specific high-risk HPV genotypes that may contribute to CVD and implement vaccine strategies as a modifiable risk factor for the reduction of CVD in addition to prevention of anogenital cancers.” – by Darlene Dobkowski

Disclosures: The authors report no relevant financial disclosures.

Women with high-risk HPV had an increased risk for CVD, especially in those with metabolic syndrome and obesity, according to a study published in Circulation Research.

“A better understanding of high-risk HPV as a risk factor for cardiovascular disease and possible combined effects of high-risk HPV, obesity and metabolic syndrome in increasing cardiovascular disease risk may help improve preventive strategies and patient outcomes,” Seungho Ryu, MD, PhD, professor at Kangbuk Samsung Hospital at Sungkyunkwan University School of Medicine in Seoul, South Korea, said in a press release.

Eun-Jeong Joo, MD, PhD, of the division of infectious diseases at Kangbuk Samsung Hospital at Sungkyunkwan University School of Medicine, and colleagues analyzed data from 63,411 women (mean age, 40 years; mean BMI, 22 kg/m2) without CVD at baseline from the Kangbuk Samsung Health Study.

Women completed questionnaires to collect information on demographics, alcohol consumption, smoking status, education level, physical activity, family history of CVD and medical history of CVD or cancer. Physical examinations were also performed to measure BP, height and weight, in addition to collect blood samples and conduct high-risk HPV tests.

The primary outcome of interest was incident CVD, defined as the first diagnosis for CVD including stroke, ischemic heart disease and transient ischemic attack. Follow-up was conducted for 261,598.9 person-years and a median duration of 4.4 years.

Of the women in the study, 7.6% had high-risk HPV. During follow-up, 1,122 cases of new-onset CVD were diagnosed with an incidence rate of 4.3 per 103 person-years.

After adjusting for age, the HR for women who were high-risk HPV-positive vs. those who were high-risk HPV negative was 1.26 (95% CI, 1.03-1.53). A significant relationship between HPV and CVD persisted after adjusting for possible confounders and high-sensitivity C-reactive protein (HR = 1.25; 95% CI, 1.03-1.52). This association was stronger in women with obesity (P for interaction = .02) and metabolic syndrome (P for interaction = .05).

Women with high-risk HPV and without obesity had an increased risk for incident CVD vs. those without high-risk HPV (HR = 1.1; 95% CI, 0.87-1.39). The risk then increased in women with high-risk HPV and obesity (HR = 1.73; 95% CI, 1.19-2.51). Similar results were seen in women without metabolic syndrome (HR = 1.09; 95% CI, 0.87-1.36) and those with metabolic syndrome (HR = 1.99; 95% CI, 1.28-3.08).

“This suggests that high-risk HPV might affect CVD risk when accompanied by obesity or [metabolic syndrome],” Joo and colleagues wrote. “Further studies are required to identify the specific high-risk HPV genotypes that may contribute to CVD and implement vaccine strategies as a modifiable risk factor for the reduction of CVD in addition to prevention of anogenital cancers.” – by Darlene Dobkowski

Disclosures: The authors report no relevant financial disclosures.

    Perspective
    J. Brent Muhlestein

    J. Brent Muhlestein

    This is a confirmatory study of a cross-sectional study that was done about 10 years ago finding the same thing — patients who were positive for high-risk HPV were more likely to have had heart troubles.

    In this study, researchers assessed a group of women without previously known heart disease and compared those who were HPV-positive to those who were HPV-negative. The average age was about 33 years. That is an age in which women do not generally get heart disease yet, even if they are at high risk.

    The length of follow-up was 5 years. That is not a long follow-up for that young of a population.

    There were not a whole lot of events in this population of almost 60,000 people, but there was a statistically greater number of adverse CV events during follow-up among the women who tested high-risk HPV-positive.

    My conclusion is that there is a small but definite increase in the risk for future CVD among women who are exposed to high-risk HPV, and the risk is even greater among those high-risk HPV-positive women who also have metabolic syndrome.

    There have been discussions regarding whether women should get vaccinated when they are young. The findings in this study probably provide another reason to consider getting the vaccination. Getting the vaccination does not necessarily guarantee that the associated increase in cardiovascular risk will not occur, but it probably will. Certainly, the vaccination has been shown to prevent cervical cancer, and here is another possible reason to do the vaccination.

    I do not think there is a specific antiviral drug recommended after a patient has the disease. The major treatment strategy is prevention by vaccination.

    Women who have HPV who get heart disease should be treated the same way as you would anybody else who gets heart disease. You might consider starting somebody on a statin sooner if they are HPV-positive, considering it is a risk factor. It is not a huge, powerfully positive risk factor by itself; the HR was about 1.25. It is not as bad as having diabetes or smoking, but it is another risk factor that one might add into one’s thought processes as to whether to begin somebody on statin therapy maybe even sooner than later.

    It might be good to do an observational study on vaccinated patients, but it will take a long time. Then it would be useful to do more basic science studies to understand the mechanism. There is a proposed mechanism that pathogenic HPV affects P52, which is a marker that is known to be associated with CAD. If we knew the mechanism better whereby this risk occurs, that might lead us to better directed treatments.

    This is further evidence that there is an infectious component associated with CAD. In the past, it has been documented. Intracellular bacteria chlamydia pneumoniae was associated with CAD and is found to grow in atherosclerotic plaque in many cases. Unfortunately, the antibiotic treatment did not work because we did not have an antibiotic that was effective in eradicating chlamydia pneumoniae from the atherosclerotic plaque, although you can treat the chlamydia pneumoniae in the lungs.

    Cytomegalovirus was also associated with increased risk for CAD complications.

    Infections still may play a role. We need to keep doing research in the whole infectious area to try to find ways to further define it and perhaps find ways to improve our care by understanding these infectious associations.

    • J. Brent Muhlestein, MD
    • Co-Director of Cardiovascular Research
      Intermountain Medical Center Heart Institute, Salt Lake City

    Disclosures: Muhlestein reports no relevant financial disclosures.