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HPV infection linked to MI, stroke in women, inflammation
October 25, 2011 Steve Stiles

Galveston, TX - Women with evidence of human papillomavirus (HPV) infections in a cross-sectional cohort analysis were also significantly more likely to have a history of MI or stroke, report investigators in the November 1, 2011 Journal of the American College of Cardiology [1].

The association of HPV with CV events, which was especially close for women with cancer-associated HPV, was independent of CV risk factors and treatments, comorbidities, and C-reactive protein levels in 2450 women with National Health and Nutrition Examination Survey (NHANES) 2003-2006 data.

The finding "indicates that conventional risk factors cannot fully explain the relation of HPV to CVD and that presence of HPV infection, especially cancer-associated genotypes, is a strong and independent correlate for CVD. To the best of our knowledge, there is no previous report on the association between HPV and CVD," write the authors, Drs Hsu-Ko Kuo and Ken Fujise (University of Texas Medical Branch, Galveston).

"In addition to being a causative pathogen for cervical cancer, HPV appears to have roles in the management and prevention of CVD among women. Detecting the presence of an HPV infection may be useful in identifying and targeting women at risk for subsequent CVD who may require additional attention to avoid the development of cardiovascular events," the group writes.

Also, "our findings may serve as a theoretical basis for additional benefit in cardiovascular health with HPV vaccination for women."

The authors acknowledge a number of important limitations beyond the lack of longitudinal data, including limitation to women and reliance on self-reported CV diagnoses.

According to an accompanying editorial [2], "a large variety of chronic infectious agents have been associated with atherosclerotic cardiovascular disease and have been confirmed in many studies. However, despite more than 20 years of intense research into the subject, the proposal that chronic infectious agents participate to an important extent in the development and progression of atherosclerosis remains just a hypothesis, neither proven nor disproven."

The current analysis is cross-sectional and so can't show whether HPV causes CV disease, but it does "suggest evidence of a causal relationship," writes the editorialist, Dr Joseph B Muhlestein (Intermountain Medical Center, Murray, UT). "Additional large prospective studies in women of all ages should be performed to confirm or refute this report." Muhlestein was an early researcher in this area and helped lead the exploration of antibiotic therapy aimed at Chlamydia pneumoniae as a possible treatment for cardiovascular disease.

In the analysis, vaginal swab specimens from the women (mean age 38) were sent for HPV DNA testing; 46.6% were positive. Of the entire cohort, 60 women (about 2.5%) reported that they had previously been diagnosed with MI or stroke; 39 were HPV DNA positive and 21 were negative.


a. Adjusted for age, race, smoking, alcohol consumption, sex behavior (practice of vaginal, oral, or anal sex), lung disease, liver disease, thyroid disease, estimated glomerular filtration rate, sexually transmitted disease, history of cervical cancer, and history of all other cancer

b. Further adjusted for hypertension, diabetes, waist circumference, triglycerides, high-density lipoprotein cholesterol, log-transformed levels of C-reactive protein and urinary albumin-to-creatinine ratio, and use of antihypertensive agents or cholesterol-lowering medications

The study, according to Muhlestein, "adds another important infectious candidate to the list of agents associated with the development, progression, or destabilization of atherosclerotic cardiovascular disease. This finding reemphasizes the potential roles that a variety of chronic infectious agents may play in the pathogenesis of atherosclerosis. Despite setbacks experienced in a number of clinical trials designed to treat patients based on the 'infectious hypothesis,' it still lives on, and slowly, progress is being made."


This sounds like the gut bacteria causing inflammation discussion in HIV!

More than 50 species of bacteria found in atherosclerotic plaque

February 22, 2006 Sue Hughes

Kiel, Germany - Atherosclerotic plaque contains a far more diverse range of bacteria than previously thought, a new study has shown [1]. This has led to renewed suggestions that infective agents could cause or worsen atherosclerotic disease, but experts in the field remain skeptical.

Dr Jeffery Anderson (University of Utah, Salt Lake City), who was not part of this study but has been one of the major players in this field, told heartwire: "This provocative study may breathe a little more life into the hypothesis that bacteria cause atherosclerosis, but it is far more likely that these bugs are just innocent bystanders."

The study, published in the February 21, 2006 issue of Circulation, was conducted by a group led by Dr Stephan Ott (Christian-Albrechts-University, Kiel, Germany). They searched for bacterial DNA in atherosclerotic tissue obtained through catheter-based atherectomy of 38 patients with CHD and control material from 15 postmortem patients and 11 organ donors who did not have heart disease.

Bacterial DNA was found in all CHD patients but not in any control material or in any of the normal/unaffected coronary arteries. The atherosclerotic tissue taken from the CHD patients was found to contain more than 50 types of bacteria, including Staphylococcus, Proteus vulgaris, Klebsiella pneumoniae, and Streptococcus species. A large degree of diversity was seen in individual atheroma samples, with DNA from between five and 22 different bacterial species found in each single specimen.

Chlamydia pneumoniae, which has been the focus of most interest so far in atherosclerosis, was found in 51.5% of CHD patients, but the other commonly implicated pathogens-Mycoplasma and Helicobacter-were not observed.

The authors conclude that diverse bacterial colonization may be more important than a single pathogen in atherosclerosis. While they say their findings do not allow the conclusion that bacteria are the causative agents in the pathogenesis of CHD, they suggest that bacterial agents could have secondarily colonized atheromatous lesions and could act as an additional factor accelerating disease progression.

They write: "The high overall bacterial diversity in coronary artery plaques, in combination with large interindividual differences, suggests that CHD is no monoinfectious disease caused by a single, specific pathogen. Our results are compatible with the hypothesis that infectious agents could be secondary factors that lead to the progression of lesions in the vessel wall through secondary colonization of atheromatous material."

Still no evidence of a causal role

In an accompanying editorial, Drs Joel Katz (Brigham and Women's Hospital, Boston, MA) and Richard Shannon (Allegheny General Hospital, Pittsburgh, PA) say the findings of this study suggest that a "conspiracy" of bacterial pathogens, as opposed to a single infection, is involved in atherogenesis, which may help to explain the inefficacy of antibiotics, such as macrolides or fluoroquinolones, in clinical trials [2].

But they add that it seems highly improbable that as many as 12 different bacteria actively infected the coronary vasculature, leading to inflammation and atherosclerosis, and that the bacterial DNA detected in this study could have just been left there by inflammatory cells.

In an interview with heartwire, Shannon explained that the techniques used in this study picked up small pieces of bacterial DNA-not necessarily whole functioning organisms. "Inflammatory cells respond to plaque, but if they have previously been mopping up bacteria somewhere else in the body they could deposit those bacteria in the plaque when they reach it. The bacteria could then form what is known as a biofilm-they just sit there but do not actively replicate or cause infection.

"While the observation in this study that the burden of bacteria in atherosclerotic plaque is much greater and more diverse than previously thought is certainly interesting, there is still no evidence that these bacteria play a causal role in atherosclerosis," Shannon continued.

Noting that no bacteria were found in the arteries of control subjects who did not have CHD, Shannon pointed out that most people without CHD would still have some early atherosclerosis, so this seems to suggest that bacteria are not necessary to start the atherosclerotic process.

"I don't think this study sheds any light on whether antibiotics will be helpful. Yes, it is conceivable that there could be some species of bacteria in the plaques that weren't killed by the antibiotics that have been tested in clinical trials. But if this is the case, we would need several drugs to eradicate all the different bacteria, and this would cause problems of its own," he told heartwire. "It is far more likely that the bacteria are just Trojan horses and are not causing the atherosclerosis. The inflammatory pathways are the real target that we should be focusing on," he added.

Anderson: Probably just innocent bystanders

Anderson has similar opinions. He told heartwire that this study was "novel and provocative" in that it was the first time that such a wide range of bacteria had been found in the atheromatous plaque. "But several major trials have shown no effect of several quite broad-spectrum antibiotics, which would have killed most of the bacteria found in this study. So all that leads me to believe that these bacteria are innocent bystanders."

He added that this study does raise a small possibility that there may be some bacteria that could be causing CHD that did not respond to the antibiotics tried so far, but it is far too early to be getting excited about this idea again. "It is far more likely that the atherosclerotic plaque is just a good garden for bacteria, and that rather than bacteria causing the plaque, the plaque attracts the bacteria. While this could add a little to the whole inflammatory process, it does not seem from the antibiotic studies conducted that the bacteria are the root cause. So even after this study, I would still say that antibiotics are out in heart disease," Anderson commented.

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