Pathophysiology of Aortic Stenosis and Future Perspectives for Medical Therapy

Zheng, Kang; Tzolos, Evangelos; Dweck, Marc R

doi:10.1016/j.ccl.2019.09.010

Cited by 53 publications

(61 citation statements)

References 129 publications

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“…However, as calcium begets calcium, Lp(a) lowering is less likely to abrogate the accelerated calcification phase towards clinically overt AVS. 18 This notion is in line with previous trials which found low-density lipoprotein cholesterol (LDL-C) lowering with statins and/or ezetimibe to be an unsuccessful strategy to attenuate AVS progression, 19–21 despite LDL-C being implicated in the development of AVS. Namely, a recent post-hoc subanalysis of the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial indicated that simvastatin/ezetimibe seemed to impede aortic jet velocity progression in a subgroup of patients with mild stenosis and high baseline LDL-C levels, whereas those who already had moderate stenosis and low baseline LDL-C did not benefit.…”

Section: Discussionsupporting

confidence: 82%

Lipoprotein(a) is robustly associated with aortic valve calcium

Kaiser

Singh

Zheng

et al. 2021

Heart

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ObjectivesTo investigate the prevalence and quantity of aortic valve calcium (AVC) in two large cohorts, stratified according to age and lipoprotein(a) (Lp(a)), and to assess the association between Lp(a) and AVC.MethodsWe included 2412 participants from the population-based Rotterdam Study (52% women, mean age=69.6±6.3 years) and 859 apparently healthy individuals from the Amsterdam University Medical Centers (UMC) outpatient clinic (57% women, mean age=45.9±11.6 years). All individuals underwent blood sampling to determine Lp(a) concentration and non-enhanced cardiac CT to assess AVC. Logistic and linear regression analyses were performed to investigate the associations of Lp(a) with the presence and amount of AVC.ResultsThe prevalence of AVC was 33.1% in the Rotterdam Study and 5.4% in the Amsterdam UMC cohort. Higher Lp(a) concentrations were independently associated with presence of AVC in both cohorts (OR per 50 mg/dL increase in Lp(a): 1.54 (95% CI 1.36 to 1.75) in the Rotterdam Study cohort and 2.02 (95% CI 1.19 to 3.44) in the Amsterdam UMC cohort). In the Rotterdam Study cohort, higher Lp(a) concentrations were also associated with increase in aortic valve Agatston score (β 0.19, 95% CI 0.06 to 0.32 per 50 mg/dL increase).ConclusionsLp(a) is robustly associated with presence of AVC in a wide age range of individuals. These results provide further rationale to assess the effect of Lp(a) lowering interventions in individuals with early AVC to prevent end-stage aortic valve stenosis.

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Section: Discussionsupporting

confidence: 82%

Lipoprotein(a) is robustly associated with aortic valve calcium

Kaiser

Singh

Zheng

et al. 2021

Heart

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“…CAVD is a progressive disease, and its most frequent clinical manifestation is AVS. The incidence of CAVD exponentially increases with age [ 13 ], and CAVD was previously considered as a primary outcome of aging. However, recent studies have discovered that CAVD is actually an active pathophysiological process caused by progressive inflammation, lipid deposition, and calcification of the valve, although the exact pathogenesis of the disease is not clearly understood [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Correlation Between Plasma Matrix Metalloproteinase-28 Levels and Severity of Calcific Aortic Valve Stenosis

Zhou

Guo

et al. 2020

Med Sci Monit

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Background Calcific aortic valve disease is a common cardiovascular disorder worldwide. This study aimed to investigate the correlation between plasma matrix metalloproteinase-28 (MMP-28) levels and the severity of calcific aortic valve stenosis. Material/Methods Calcific aortic valve stenosis patients who were admitted to the heart center of our hospital between January 2016 and January 2019 to undergo surgery were successively enrolled in this study (55 males and 24 females with an average age of 58.5±9.6). Information on echocardiography, plasma MMP-28 levels, and other clinical data of the patients was retrospectively collected. Results The average plasma MMP-28 level was 2.43±2.22 ng/mL (range, 0.22–8.27 ng/mL). Plasma MMP-28 levels in patients with mild (n=24), moderate (n=31), or severe (n=24) aortic valve stenosis were 0.74 (0.25–2.23), 1.46 (0.50–3.22), and 4.13 (1.54–6.18) ng/mL, respectively, indicating that the patients with severe aortic valve stenosis had significantly higher MMP-28 levels than the patients with moderate or mild aortic valve stenosis (both P <0.01). Regression analysis using the general linear model further revealed that plasma MMP-28 level was correlated with the peak blood flow velocity and mean pressure gradient of the transaortic valve, and the correlations were statistically significant (both P <0.01). Conclusions MMP-28 level is significantly elevated in severe cases of calcific aortic valve stenosis. Moreover, plasma MMP-28 levels are positively correlated with the mean pressure gradients and peak blood flow velocity of the transaortic valve.

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“…It is important to note that progressive aortic valve narrowing with coexistent left ventricular pressure overload and subsequently left ventricular hypertrophy may transition to heart failure and development of symptoms [19].…”

Section: Aortic Stenosismentioning

confidence: 99%

Reappraising the spectrum of bleeding gastrointestinal angioectasia in a degenerative calcific aortic valve stenosis: Heyde’s syndrome

2021

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Background The occurrence of bleeding gastrointestinal angioectasia in elderly patients with degenerative calcific aortic stenosis is one of the most challenging clinical scenarios. A number of studies have shown that this clinical phenomenon is known as Heyde’s syndrome. Main body of the abstract The pathogenesis of Heyde’s syndrome is mainly due to the loss of high-molecular-weight von Willebrand factor (HMW vWF) multimers, as a consequent fragmentation of HMW vWF multimers as they pass through the stenosed aortic valve leading to acquired von Willebrand syndrome type IIA. Aortic valve replacement has proven to be a more effective management approach in the cessation of recurrent episodes of gastrointestinal bleeding. Short conclusion Physicians should have a high index of suspicion when dealing with elderly patients with established aortic stenosis presenting with iron deficiency anemia or unclear gastrointestinal bleeding. Parallel consultations between different specialties are essential for appropriate management.

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Pathophysiology of Aortic Stenosis and Future Perspectives for Medical Therapy

Cited by 53 publications

References 129 publications

Lipoprotein(a) is robustly associated with aortic valve calcium

Lipoprotein(a) is robustly associated with aortic valve calcium

Correlation Between Plasma Matrix Metalloproteinase-28 Levels and Severity of Calcific Aortic Valve Stenosis

Reappraising the spectrum of bleeding gastrointestinal angioectasia in a degenerative calcific aortic valve stenosis: Heyde’s syndrome

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