Orlando, FL - A team of Belgian researchers has made the surprise discovery that women who have used oral contraceptives (OCs) for some time appear to be at increased risk of atherosclerosis in the carotid and femoral arteries. They also found that those taking the pill had three times higher C-reactive protein (CRP) levels than those not using it.
Dr Ernest Rietzschel (Ghent University, Belgium) reported the findings at the American Heart Association (AHA) 2007 Scientific Sessions last week. He told heartwire: "This is the first time that this has been documented. It was an accidental finding. We were stunned by the large elevations in CRP that you see in women taking the pill, so we then performed a safety analysis to see whether there was a link between past pill use and atherosclerosis measured by echo in both the carotid and femoral arteries. Our null hypothesis was that we would see no effect, but in hindsight that was probably naive."
He stressed, however, that this research should not mean that women should cease using oral contraceptives: "I'm certainly not advocating stopping use of the pill," he noted. First, the findings need to be replicated, "that's really important," he said, "and then we need more research. It's staggering that for a drug that is being used by 80% of women, there is so little information about the long-term safety. That's really incredible."
OCs an important factor in global atherosclerotic burden
Rietzschel and colleagues started out by assessing novel risk factors for atherosclerosis in women participating in the Asklepios study, a blinded sample of men and women volunteers aged 35 to 55 years in the Belgian population who were free from overt cardiovascular disease. Rietzschel said that there has been one prior report of increased CRP in OC users, from the Cardiovascular Risk in Young Finns study.
Of 1301 women (mean age 45.7 years) in Asklepios, 27.4% were taking OCs and 10.0% were taking hormone replacement therapy (HRT). Past OC use was much higher, however, with 81% of women having taken it for at least one year, with a median exposure of 13 years.
After multivariate adjustment, women who were not taking OCs or HRT had high-sensitivity CRP of 1.0 mg/L compared with 1.2 for those currently taking HRT and 3.3 for women currently taking OCs. Effects on other inflammatory markers, such as interleukin-6, were far less pronounced, the researchers note.
"Contraceptive therapy is a major cause of CRP rise. The magnitude of CRP rise (threefold) far exceeds other population-prevalent noninfectious stimuli and is much larger than the CRP rise for HRT. Future research should take into account this effect when reporting CRP data in women, aim to qualify its biological significance, and assess the potential of CRP as a tool to select those women at high thrombotic risk under hormonal therapy," Rietzschel et al say.
This finding spurred Rietzschel and his team to look at past OC use, "something we might not have considered a plausible candidate for atherosclerosis," he explained to heartwire. After multivariate adjustment, they found the odds ratios (OR) per 10 years of OC exposure were 1.17 for carotid plaque and 1.28 for femoral plaque. They also looked at prevalence of bilateral disease as a more stringent phenotype of atherosclerosis and found ORs per 10 years of OC exposure of 1.42 for carotid plaque and 1.34 for femoral plaque.
"Use of contraceptive therapy is very common and is associated with an unexpected increase in the prevalence of carotid and femoral atherosclerosis in otherwise young, apparently healthy women. Our data suggest a 20% to 30% increased prevalence of plaque in the carotid and femoral arteries per 10 years of OC exposure. In the light of widespread and usually prolonged OC use, these results suggest OC use could be an important factor in the global atherosclerotic burden," the scientists observe.
A unique opportunity to intervene
While Rietzschel stresses that women should not stop taking the pill on the basis of this research, he says, "Perhaps women should be wary of taking the pill for longer than they need to. At a certain point, don't prolong it out of habit."
Women seeking oral contraception also present a unique opportunity for doctors to give advice on the prevention of cardiovascular disease at an early age, he notes. "Young women have an idea that they won't succumb to cardiovascular disease, which is entirely wrong, because more women die of cardiovascular disease than men. Maybe this is a good time to start talking with young women. Okay, you want to take the pill, but think about the long-term implications. You should stop smoking, check your weight, and be more physically active. Also, we know the pill has effects on blood pressure and lipid profiles, so these should be checked."
The pharmaceutical industry must also contribute, Rietzschel says: "We would like to ask them to develop safer pills." He says he has been approached by some OC manufacturers following his presentation last week but declined to say which ones.
At this time, it is also impossible to say whether any specific type of pill is more hazardous than any other, he noted. "We know that estrogen has a beneficial effect on lipid profiles and it is probably the progestin component of the pill that has adverse effects on lipids, but with regard to the blood-pressure rises seen, it's not clear what raises BP."