Being International Women’s Day I raise a topic that has bothered me for years. As a preventative non-invasive cardiologist I have had the privilege of seeing many women age 35-65 years who look particularly gorgeous on the “outside” but have advanced sub-clinical atherosclerosis on the “inside”. A common feature in these women is prolonged use of oral contraception (OC) during their lives.
To introduce discussion on OC use and “premature” atherosclerosis I show you a carotid ultrasound of a healthy 60 year woman free of sub-clinical atherosclerosis.
This is a longitudinal view of the carotid artery with “edge-detection” software tracking the intima-media (IM) interface. In this woman the IM is pristine reflecting no thickening, no irregularity and no plaque (free of sub-clinical disease).
By contrast this 45-year-old woman has a very large 0.24 cm “soft” atherosclerotic plaque at the origination of the internal carotid artery.
This plaque has filled 50% of the diameter of the proximal internal carotid artery and thus reflects quite severe (advanced) sub-clinical atherosclerosis in a “well woman” who has had prolonged exposure to oral contraceptive therapy (OC) and was at the time of this examination still taking a low dose mixed estrogen/ progestogen containing OC .
So what data is available to suggest an association of OC to atherosclerosis?
Jamil and Siddiq write a compelling article:
“Comparison of CVD risk associated with the long term use of contraceptives in young females” J App Pharm Sci. 2012; 2 (11): 062-066.
They correctly point out abnormal lipid profiles have been associated with major risk factors for cardiovascular disease (CVD) which is one of the most dominant causes of death in the world and is mainly due to vascular atherosclerosis.
I have previously indicated that cardiovascular disease is the leading cause of adult mortality, with women comprising 55% of the epidemic.
Extensive use of hormonal contraception by females through their reproductive life has led to the concern about the effects of oral contraceptives on the risk factors for coronary heart disease. OC-induced changes in both carbohydrate and lipoprotein risk factors may contribute to the increased risk of vascular disease as orally administered estrogens increase hepatic triglyceride synthesis and VLDL secretion. Estrogens increase the rates of elimination of LDL, VLDL and chylomicrons; suppress the synthesis of key enzymes of lipoprotein metabolism, hepatic and lipoprotein lipase, and increase synthesis of the principal apo-protein of HDL, Apo-A1. Interestingly though, although estrogens have been shown to elevate HDL, the subtype of HDL has been shown to be “non-functional” in reverse transporation of atherogenic LDL from the plaque back to the liver. So the high HDL in women taking estrogen based hormone therapy may be misleading and lead the individual (and the doctor) into a false sense of security.
So oral contraception usage has been found to be associated with adverse findings in several metabolic, cardiovascular and inflammatory parameters, which is consistent with an increased future risk of cardiovascular and metabolic disease. These findings should invite more criticism of recent trends that encourage the prescription of oral contraceptives for years during reproductive life and especially in pre-menopausal women.
In general, progestogens oppose estrogen effects on lipoproteins according to type and dose leading to a range of different lipoprotein profiles including abnormally low HDL level; abnormally high LDL level and an increase in the LDL: HDL cholesterol ratio. The decline in HDL is associated more with androgenic progestins.
This study compared the extent of cardiovascular atherosclerotic risk associated with the lipid metabolism in women using hormonal contraceptives in an urban population of low socio-economic group. The conclusion was that the use of OC’s was associated with the highest atherogenic index and the authors suggested that hormonal contraception should be used under close monitoring until further studies conducted to completely eradicate the risk associated with hormonal preparations.
Perhaps more compelling research comes from a team of Belgian researchers who made the surprise discovery that women who have used oral contraceptives (OC’s) 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.
This data was presented by Dr Ernest Rietzschel (Ghent University, Belgium) at the American Heart Association (AHA) 2007 Scientific Sessions. This was the first documentation of the large elevations in CRP seen in women taking the pill.
It’s staggering that for a drug that is being used by 80% of women at some point in their lives, there is so little information about the long-term safety. This study is important and provocative, because it raises new questions about the long-term safety of a widely used class of drugs.
CRP increased threefold in those taking OC’s:
Rietzschel and colleagues started out by assessing novel risk factors for atherosclerosis in women participating in the Asklepios study, a blinded sample of women volunteers aged 35 to 55 years in the Belgian population who were free from overt cardiovascular disease.
Of 1301 women (mean age 45.7 years) in Asklepios, 27.4% were taking OC’s 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 OC’s 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 OC’s.
OC’s an important factor in global atherosclerotic burden:
The researchers found an increase in the prevalence of carotid and femoral atherosclerosis in this group of otherwise young, apparently healthy women. Their 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 suggested OC use could be an important factor in the global atherosclerotic burden.
Perhaps the article which raises the most concern is this very recent paper in NEJM June 2012. A massive number of women taking OC were followed (1,626,158) contributing 14,251,063 person-years of observation during which 3311 thrombotic strokes (21.4 per 100,000 person-years) and 1725 myocardial infarctions (10.1 per 100,000 person-years) occurred.
The table taken from the paper shows the STAGGERING increase in incidence in stroke and coronary deaths with increasing age and exposure to the OC’s.
So my concern:
For a drug that is used widely amongst young women there seems to be some data suggesting increased lifetime risk of atherosclerosis predisposing to increased morbidity and mortality in the woman’s lifetime.
Women seeking oral contraception present a unique opportunity for doctors to give advice on the prevention of cardiovascular disease at an early age. “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 to 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 and managed.”