Besides, recent studies have emphasized the effect of apolipoprotein(a) as an anti-inflammatory component of HDL which does not depend on HDL cholesterol level [11,27]
Besides, recent studies have emphasized the effect of apolipoprotein(a) as an anti-inflammatory component of HDL which does not depend on HDL cholesterol level [11,27]. symptom-free period which can last for several decades. Aortic Azilsartan medoxomil monopotassium valve replacement surgery is necessary when the symptoms occur. The lipid-lowering therapy effect on stopping or at least slowing down the progression of DAS was studied. However, the results of the conducted clinical trials are controversial. In addition, calcium homeostasis, bone metabolism and calcinosis-reducing medication are being studied. Although prospective randomized clinical trials have not demonstrated any positive effect of statins used for slowing progression of the disease, statins are still recommended for patients with dyslipidemia. Recent study has suggested that a specific modification of treatment, based on severity of disease, may have a beneficial effect in patients with aortic sclerosis and mild DAS. New clinical studies analyzing new treatment possibilities which could correct the natural course of the disease and reduce the need for aortic valve replacement by surgery or transcatheter treatment interventions are needed. = 0.03) [27]. Even in cases when intensive lipid-reducing therapy is applicated and recommended LDL levels are achieved, DAS progresses twice as fast as for patients without MS [11]. Many studies proving the effect of lipid metabolism disorders have been conducted. In 1997, it was determined in vitro that oxidized lipids stimulate calcinosis [28], whereas a study conducted on animals has proved that hypercholesterolemia induced calcinosis and DAS [29]. Lipids have a significant role in pathogenesis of DAS via molecular processes of cells, e.g., Wnt/Lrp5 and RANK/RANKL/osteoprotegerin which induce transition of valvular myofibroblasts to osteogenic components due to which accumulation of bone tissue begins in valves [17,30]. It was determined in CHR and MONIKA/KORA studies that cholesterol and related lipoproteins are independent DAS risk factors [31,32]. Parisi et al. analyzed the interaction of lipids, inflammatory process and DAS. It was proven that increased LDL levels induce development of not only CAD, but also DAS. It was determined that lipids activate biological molecular processes as well as activate calcinosis of aortic valve. Lipid metabolism disorders influence calcinosis of blood vessels and valves as well as altered metabolism of bone proteins [30]. The fact that hypercholesterolemia influences not only CAD but also calcinosis of the root of aorta Azilsartan medoxomil monopotassium and, especially, aortic valve has been proven for patients suffering Azilsartan medoxomil monopotassium from homozygous familial hypercholesterolemia. Lp(a) concentration is an independent risk factor for development of aortic valve calcification, DAS and unfavorable prognosis [7]. In EPIC-Norfolk and two prospective general population studies (the Copenhagen City Heart Study (CCHS) (1991C2011; = 10,803) and Copenhagen General Population Study (CGPS) (2003C2011; = 66,877) determined that elevated Lp(a) levels increase the risk of valve calcinosis [33,34]. An analysis of 129 Dutch people suffering from familial hypercholesterolemia was conducted recently and it was determined that elevation of Lp(a) by 10 mg/dL (0,259 mmol/L) is associated with 11% likelihood of DAS development [29]. MESA study has proven a significant correlation between Lp(a), the degree of calcinosis of aortic valve and progression of DAS irrespective of patients race, age, sex, arterial hypertension, diabetes, smoking, HDL and TG [35]. Previous study also pointed out genetic ties between Lp(a) and DAS [36]. CHARGE Azilsartan medoxomil monopotassium study determined that genetic variants of Lp(a) are strongly related to calcinosis of aortic valve and DAS [37]. The study has proven that increase of Lp(a) directly induces calcinosis of aortic valve and progression of DAS [38]. The results of the study promoted assessment of Lp(a) as a factor which can modify AV disease. ILF3 Thanassoulis et al. argue that targeted Lp(a) therapy may become a new opportunity to treat DAS [39]. Penetration and oxidation are significant pathogenic mechanisms which stimulate inflammatory reaction in aortic valve endotelium. Close relationship between lipids, inflammation and DAS was determined [7,11,12]. LDL and Lp(a) infiltrate the location of injury and oxidize. These oxidized lipoproteins are cytotoxic and they stimulate inflammatory response and mineralization [2,7,12,30]. Genetic relationship between LDL and DAS has been proven by other studies. Smith et al. have determined a genetic causal relationship between elevated LDL concentration and calcinosis of aortic valve as well as DAS. It was identified that LDL, but not HDL or TG, is significantly related to DAS (HR 1.28; 95% CI, 1.04C1.57; = 0.02). Genetic risk score (GRS) of LDL (but not that of HDL or TG) was significantly associated with calcinosis of aortic valve in CHARGE study (OR 1.38; 95% CI, 1.09C1.74; = 0.007) as well as with DAS in MDCS study (HR 2.78; 95% CI, 1.22C6.37; = 0.02). GRS of LDL was significantly related to calcinosis of aortic valve (= 0.03) and AS (= 0.009) [37]. Recent study confirmed the association between 2 LPA variants (rs10455872 and rs 3798220) and aortic stenosis. With this study it has been proven that individuals with two.