Reducing the risk of aortic stenosis: be healthy, be calcium free!

This editorial refers to ‘High life’s essential 8 score is associated with lower aortic valve calcification’, by M. Gui et al. https://doi.org/10.1093/eurjpc/zwaf285 Aortic stenosis (AS) is the leading cause of degenerative valvular heart disease (VHD) in Europe and North-America, with a prevalence that rises as the population ages.1 Regardless of its severity, AS is due to aortic valve calcification (AVC), a chronic and progressive disease characterized by calcification of the aortic leaflets with a complex pathophysiology.2 When the patients become symptomatic with severe AS, European and American guidelines recommend (class I,A) to treat AS with either surgical aortic valve replacement or transcatheter aortic valve implantation, depending on age and comorbidities after Valvular Heart Team decision.3 These two approaches are highly efficient to correct AS. However, to date, there is still no existing medical approach that may prevent and/or halt AVC and its potential progression to severe symptomatic AS. In this issue from Gui et al.,4 which included 30 561 patients (mean age 63 ± 11 years, 80% of male) from the Kailuan prospective cohort (10 hospitals in China) with an available transthoracic echocardiography, the authors aimed to explore the relationship between Life’s Essential 8 (LE8) and AVC. In order to increase public awareness on cardiovascular health, the American Heart Association introduced in 2022 the LE8, a comprehensive set of metrics that includes four health behaviour (diet, sleep, physical activity, and smoking) and four health factor indicators (body mass index, blood pressure, glycaemia, and blood lipids). Previous studies already highlighted that the higher the LE8, the lower the risk of coronary artery disease, atrial fibrillation, and heart failure, but it remained unclear whether this relation was true in the field of AS. In particular, they found that (i) AVC was detected in 12.6% of the patients with a higher prevalence (15.3%) in patients with low LE8 score, in other terms, the lower the LE8, the higher the rate of AVC detection (P < 0.001), (ii) for each one standard deviation increase in LE8 score, the presence of AVC decreased by 23%, (iii) except for sleep or smoking status, each of the component of the LE8 score was independently associated with AVC presence, especially blood pressure and dyslipidemia. Even if AS pathophysiology remain complex and partially understood, several studies already emphasized the burden of cardiovascular risk factors on AVC development, especially because there are similarities between atherosclerosis process and the progression of AS.2 In the PARTNER 3 trials (surgical vs. transcatheter aortic valve replacement in patients considered at low risk), body mass index averaged 30.7 ± 5.5 kg/m2 and 31% of patients had diabetes, emphasizing that metabolic syndrome is likely in patients with AS. Moreover, genome-wide association study identified several pathways as main contributors of in AS development such as dyslipidemia, inflammation, calcification, and adiposity.5 Dyslipidemia and adiposity belong to cardiometabolic syndrome and are important part of the LE8 score. In other term, this study reinforces the well-known relationship between cardiovascular risk factors and metabolic syndrome, risky behaviour, and AVC progression.6 Especially, higher blood pressure, BMI, and dyslipidemia seem to be particularly associated with AVC. In the Cardiovascular Health Study, a history of arterial hypertension increases relative risk of AS by 23% and among older patients with AS, arterial hypertension is common, found in up to 78% of patients.1,7 Moreover, arterial hypertension per se is a risk factor for developing AS.8,9 However, in the SEAS study, AVC progression was not different between arterial hypertension and normotensive patients.10 Lipid profile is still under the spotlight in the field of AS. Indeed, several studies demonstrated a link between lipoprotein (a) [Lp(a)] circulating level and AS development and as well as between LDL cholesterol and the mineralization of the aortic valve. Proprotein convertase subtilisin/kexin type 9 inhibitors showed promising interest to reduce AVC.11 However, none of these treatments has proven its efficiency nor is recommended by any guidelines.2 Higher body mass index was also already known to be associated with higher risk of aortic stenosis.12 However, to date, there is not existing studies that evaluated the impact of weight-reduction therapy and AS progression. Taken one by one, either targeting blood pressure, BMI or using lipid-lowering therapy, randomized clinical trials or studies with a medical approach failed to prove their benefit in patients with AS or to prevent AVC progression. Even if the causal relationship between low LE8 and AVC progression cannot be proved with this study, the aforementioned results argue in favour of a combined and aggressive approach, targeting not one but several risk factors in order to reduce the risk of AVC and eventually AS. Apart from the relationship between cardiovascular risk factors/metabolic syndrome and AVC progression, this study also brings new data regarding the link between physical activity/diet and AS. Even if the relationship was lower that the factors mentioned previously (risk reduction of 6% and 9% for diet and exercise, respectively), this relation was significant in this study. However, this does not allow us to conclude whether it is physical exercise in itself that has an impact on AVC, or whether it is physical exercise that, leading to better control of cardiovascular risk factors, slows down calcifications. Indeed, it has been demonstrated that shear stress lesions and higher mechanical injury, which are potentially more important during exercise, have a negative impact on the valve structure by promoting osteogenic differentiation of valve interstitial cells, thus accelerating calcifications. Regarding diet, little is known about the type of diet that may prevent from AVC in this study. Further studies are necessary to further explore this aspect. Several limitations have to be emphasized. First, and as mentioned by the authors, not echocardiography but computed tomography is the gold standard for AVC assessment. The echo approach may have induced classification bias due to low sensitivity and specificity to detect mild AVC. And again, it would have been interesting to have aortic valve calcium score and its relationship with LE8. Secondly, echocardiography and LE8 was assessed at different time point with an averaged interval between the two exams of 0.65 years. In this interval, specific treatment, especially for diabetes of blood pressure control may have induced classification bias regarding LE8 score. Thirdly, AVC presence was evaluated in a binary way and only at one time. Since echocardiography was performed for each patient in this study, it would have been interesting to have AS severity among patients with AVC and eventually its evolution through severe AS. Indeed, little is known about the natural history of AVC and AS, and it is questionable whether patients with AVC will develop symptomatic AS and related adverse event such as heart failure and/or death. Fourth, only Chinese patients were included in this study whereas there are existing disparities regarding VHD burden worldwide. Same type of study conducted in Europe and/or North America should be setting up in order to confirm these results. To conclude, because of AS burden and prevalence is rising worldwide, a preventive approach is required in this field. This study emphasizes nicely that ‘being healthy is associated with calcium free’ in the field of AS. However, further studies are now warranted to confirm these results and to see whether a long-term strict control of cardiovascular risk factors associated with healthy behaviour may halt the progression of AVC to severe AS. None. No new data were generated or analysed in support of this research.