HOW TO KILL TWO BIRDS WITH ONE STONE (NUT OR FISH): VITAMIN D AGAINST NOT ONLY ATHEROSCLEROSIS; OLD AND NEW DRUGS AGAINST NOT ONLY PERIPHERAL ARTERIAL DISEASE
Piťha J.1, Vrablík M.2
1Department of Cardiology, Center for Cardiovascular Research Prague, Institute for Clinical and Experimental Medicine, Prague
23rd Department of Internal Medicine, 1st Faculty of Medicine, Charles University and General University Hospital, Prague
Polyvascular disease is on the rise, paradoxically due to the success of revascularization methods saving one part of the arterial bed but allowing development of atherosclerotic changes to advanced stages in another part. Detection of peripheral arterial disease (PAD) in patients with already established ischaemic heart disease had not been considered of importance until now, especially when asymptomatic – the algorithm for cardiovascular risk reduction was identical. Nevertheless, according to recent data, aggressive control of risk factors, especially of atherogenic lipoproteins, could be very effective in the prevention of subsequent serious clinical events in patients with several arterial beds involved compared to patients with “single” atherosclerosis involving only one arterial territory.
Moreover, in addition to potent lipid lowering drugs already available or under development, other components of atherosclerotic process are also considered to be the target for modification. Recent trials with anti-inflammatory strategies (canacinumab, colchicin) have proven effective in reducing the risk of atherosclerosis progression. Nevertheless, atherogenic lipoproteins and their cholesterol content are considered the principal causal risk factors of atherosclerosis, and thus, new strategies to reduce their plasma concentrations attract the attention of researchers. This holds particularly true in the current era of “crisis in confidence” in statins with growing numbers of statin (pseudo) intolerant patients. Novel small molecules (e.g. bempedoic acid, pemafibrate) might become a standard part of combination regimes of non-statin lipid-lowering approaches. Biotechnology offers new targeted therapies with more favourable efficacy/safety profile. In addition to the established monoclonal antibodies against PCSK9 (PCSK9 inhibitors), anti-sense strategies (e.g. anti-Lp(a) ASO, anti-ANGPTL3 ASO, anti-apoB ASO) are being developed. Most recently, a novel approach using RNA silencing mechanism (e.g. inclisiran, siRNA against Lp(a)) have been introduced offering not only very good safety and efficacy profiles but also showing a promise towards potential solution to the non-adherence issue. Accompanying these modern approaches, the role of nutraceuticals and vitamins is intensively and repeatedly discussed as potential modifiers of oxidative, metabolic, and other unfavourable processes. While vitamins A, E, and C bought over the counter and used as pills did not show very exciting results in the prevention of various maladies including atherosclerosis, vitamin D is still on the scene and subject of intense debate. Large controlled intervention trials are missing, but the intake of vitamin D in form of fish and/or nuts could be a valuable dietary approach, at least partially displacing less favourable nutrients from our diet. In summary, keeping our blood levels of vitamin D at desirable level could help keep our vessels and possibly also airways more resistant through various pandemics including the recent one.
In our lectures, we will discuss how to challenge atherosclerotic process in patients with polyvascular disease by modern methods including the potential preventative role of vitamin D.
Acknowledgement: MV supported by the Ministry of Health, Czech Republic – conceptual development of research organization 64165, General University Hospital in Prague, Czech Republic
JP Supported by MH CZ – DRO (“Institute for Clinical and Experimental Medicine – IKEM, IN 00023001”)