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Dr. Raphael Rosenhek ,
Statins seem to delay aortic stenosis progression through their cholesterol lowering action. It can be expected that cholesterol lowering will reduce cardiovascular events in these high-risk patients. The onset of symptoms in severe aortic stenosis might be delayed since some patients with aortic stenosis experience their symptoms due to coronary artery disease. Current available data therefore support an aggressive control of hyperlipidemia (using statins as first line therapy) in all patients with aortic sclerosis and stenosis. However, no data are available to support lipid-lowering therapies in patients with aortic stenosis who have normal cholesterol levels.
Calcific degenerative aortic valve disease is a progressive disease, encompassing the spectrum from aortic sclerosis on one side, to severe aortic stenosis on the other. All stages of the disease are increasingly being diagnosed in an ageing population. Ultimately, aortic valve replacement surgery is the only established therapy once the symptomatic, severe disease is present and it is performed at increasing rates.
Calcific degenerative aortic valve disease is by far the most frequent etiology of aortic stenosis and consists of an active progressive process(1): during the disease process, lipid infiltration occurs into the interstitial tissue were LDL and Lp(a) undergo oxidative modification. These oxidised lipoproteins stimulate inflammatory processes and finally calcification and even lamellar bone formation occur in the vicinity of these inflammatory areas.
Taking a look back at the risk factors for calcific aortic stenosis, a surprising overlap exists with atherosclerotic risk factors including hypercholesterolemia, diabetes, hypertension and smoking(2). Indeed calcific aortic stenosis shares many similarities with atherosclerosis and in particular, coronary artery disease, with a frequent coexistence of the two diseases.
Progression from aortic sclerosis to aortic stenosis has been reported to occur at non-negligible rates. Once aortic stenosis is present, the rate of hemodynamic progression is reflected by mean progression rates of around 0.25 m/s/yr for the peak aortic jet velocity and by a mean decrease of aortic valve area by about 0.15 cm2 per year. The possibility of even more rapid rates of progression needs to considered(3). Patients with calcified aortic valves especially, are at an increased risk for a more rapid hemodynamic progression – these are also the patients that are more prone to becoming symptomatic and thus also to require aortic valve replacement surgery.
Aortic stenosis is active progressive disease sharing a number of similarities with atherosclerosis. Consequently the utility of a lipid lowering therapy in these patients is being studied:
In a rabbit model, Rajamannan and colleagues have shown that hypercholesterolemia induced changes at the aortic stenosis levels which were reversed when atorvastatin was administered(4).
Four retrospective studies including between 156 and 211 patients observed significantly slower rates of hemodynamic progression in the statin-treated patients(5-8).
However, the SALTIRE-trial, which was the first prospective study randomizing patients with aortic stenosis to receive placebo or 80mg of atorvastatin yielded a negative result after a mean follow-up of 26 months(9). With 155 patients the study size was similar to the retrospective trials and also the follow-up duration was similar. The major difference of this study however was that patients who actually had a hyperlipidemia were excluded as was judged to be unethical to deprive these patients from a statin.
The recently published RAAVE-Trial, is a prospective study that has chosen a different approach. Patients were treated with rosuvastatin when they had hypercholesterolemia, according to current guidelines for the treatment of hyperlipidemia(10). The treated patients (n=61) had a mean LDL-cholesterol level of 160±33mg/dl, whereas the untreated patients (n=60) had a mean LDL-cholesterol level of 119±37 mg/dl. In this study a significantly slower rate of progression was observed for patients receiving a statin therapy. Also a correlation between change in LDL-cholesterol levels during therapy and the hemodynamic progression of aortic stenosis was found.
Even patients with aortic sclerosis have a significantly increased morbidity and mortality.
Chandra and colleagues have demonstrated, that patients with aortic sclerosis coming to an emergency department because of chest pain had a significantly worse 1-year survival than patients without aortic sclerosis(11). In a multivariate analysis however, the poor outcome was independently related to coronary artery disease, myocardial infarction at admission and to a lesser degree to CRP-levels or the presence of heart failure, not aortic sclerosis itself.
In a large population based study Otto and colleagues have shown, that aortic sclerosis and aortic stenosis to an even higher degree predict an increased morbidity and mortality(12).
Shah et al. demonstrated that patients with known coronary artery disease who have a sclerotic aortic valve as compared to patients with a normal aortic valve have a significantly higher cumulative risk for the occurrence of a myocardial infarction(13). While aortic sclerosis predicted the risk for a subsequent myocardial infarction in patients who did not receive a statin it did not predict the risk in patients on statin therapy. The authors concluded that aortic sclerosis which was present in 40% of patients with coronary artery disease was independently associated with a 2.4-fold risk of subsequent myocardial infarction and that statins may attenuate the increased risk of future infarction in these patients.
Since a significant number of patients with aortic stenosis have coronary artery disease, the onset of new symptoms might be due to a progression of their coronary artery disease. In numerous studies, statin therapy has been shown to be beneficial in stabilising atherosclerotic disease.
Recently, Alcalai and colleagues have reported an interesting series of 38 consecutive symptomatic patients with significant aortic stenosis and coronary artery disease who underwent percutaneous coronary intervention (surgery was not performed because of patient preference, high surgical risk and cardiologists recommendation)(14). After the intervention 35 of these patients reported a relief of their symptoms.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.
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Prof. R. Rosenhek Vienna, Austria Treasurer of the ESC Working Group on Valvular Heart Disease
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