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............................................................................................................................................................................. plasma cholesterol concentrations who do not qualify for treatment with statins in view of their global CV risk. However, there is a clear need for better regulation of RYR supplements. Information regarding the precise composition of these products, the quantities of their components, and their purity should be implemented.185

7.5.3 Dietary fibre Available evidence consistently demonstrates a TC- and LDL-Clowering effect of b-glucan, a viscous fibre from oat and barley. Foods enriched with these fibres or supplements are well tolerated, effective, and recommended for LDL-C lowering.186 However, the dosage needed to achieve a clinically relevant reduction in levels of LDL-C of 35% varies from 310 g per day according to the specific type of fibre.187

7.5.4 Soy The cholesterol-lowering effect of soy is generally attributed to its isoflavone and phytoestrogen content, which decreases progressively with the increasing degree of soybean processing. Soy protein has also been indicated as being able to induce a modest LDL-C-lowering effect when replacing animal protein foods. However, this was not confirmed when changes in other dietary components were taken into account.187,188

7.5.5 Policosanol and berberine Policosanol is a natural mixture of long-chain aliphatic alcohols extracted primarily from sugarcane wax.189 Studies show that policosanol from sugarcane, rice or wheat germ has no significant effect on LDL-C, HDL-C, TG, ApoB, Lp(a), homocysteine, high-sensitivity Creactive protein, fibrinogen, or blood coagulation factor levels.190 As for berberine, a recent meta-analysis evaluated its effects on plasma lipids in humans.191 The comparative evaluation of berberine and lifestyle intervention or placebo indicated that in the berberine group, LDL-C and plasma TG levels were more effectively reduced than in the control group. However, due to the lack of high-quality randomized clinical trials, the efficacy of berberine for treating dyslipidaemia needs to be further validated. Moreover, the bioavailability of the different berberine preparations is a matter of debate.187

7.5.6 n-3 unsaturated fatty acids Observational evidence indicates that consumption of fish (at least twice a week) and vegetable foods rich in n-3 fatty acids (a-linoleic acid is present in walnuts, some vegetables, and some seed oils) is associated with lower risk of CV death and stroke, but has no major effects on plasma lipoprotein metabolism.178,192 Pharmacological doses of long-chain n-3 fatty acids (23 g/day) reduce TG levels by about 30% and also reduce the post-prandial lipaemic response, but a higher dosage may increase LDL-C levels. a-Linolenic acid is less effective at altering TG levels.156,193 Recently, a significantly lower risk of ischaemic events, including CV death, was observed in patients with elevated TG levels despite the use of statins treated with 2 g of icosapent ethyl b.i.d. [twice a day].194 Other features of a healthy diet contributing to CVD prevention are presented in the Supplementary Data. 8 Drugs for treatment of

dyslipidaemias

8.1 Statins

8.1.1 Mechanism of action Statins reduce the synthesis of cholesterol in the liver by competitively inhibiting the enzyme HMG-CoA reductase, the rate-limiting step in cholesterol biosynthesis. The reduction in intracellular cholesterol promotes increased LDL receptor (LDLR) expression at the surface of the hepatocytes, which in turn results in increased uptake of LDL from the blood, and decreased plasma concentrations of LDL- and other ApoB-containing lipoproteins, including TG-rich particles.

8.1.2 Effects on lipids 8.1.2.1 Low-density lipoprotein cholesterol. The degree of LDL-C reduction is dose-dependent and varies between the different statins. A highintensity regimen is defined as the dose of a statin that, on average, reduces LDL-C by >_50%; moderate-intensity therapy is defined as the dose expected to reduce LDL-C by 3050%. Notably, there is considerable interindividual variation in LDL-C reduction with the same dose of drug.31 Poor responses to statin treatment in clinical studies are to some extent caused by poor compliance, but may also be explained by genetic backgrounds.195,196 Interindividual variations in statin responses warrant monitoring of responses on initiation of therapy. Among patients who cannot tolerate the recommended intensity of a statin because of adverse effects or those who do not reach their goal, the addition of a non-statin lipid-modifying agent to a maximally tolerated statin is recommended.197,198

8.1.2.2 Triglycerides. Statins usually reduce TG levels by 1020% from baseline values.199 More potent statins (atorvastatin, rosuvastatin, and pitavastatin) demonstrate robust lowering of TG levels, especially at high doses and in patients with elevated TGs (HTG), in whom the absolute risk, and therefore the absolute risk reduction, is larger. The mechanism of the TG-lowering effect has not been fully elucidated, but it seems to be partly independent of the LDLR pathway. It may involve the upregulation of VLDL uptake by hepatocytes, as well as a reduction of the production rate of VLDLs; these effects seem to be dependent on pre-treatment VLDL concentrations.200

8.1.2.3 High-density lipoprotein cholesterol. In a meta-analysis,201 elevations in HDL-C levels varied with dose among the respective statins; such elevations ranged from 110%. However, given the marked statin-mediated decrement in atherogenic ApoB-containing lipoproteins, the extent to which the very modest effect on HDL-C levels might contribute to the overall observed reductions in CV risk consistently observed in statin intervention trials cannot reliably be disentangled.

8.1.2.4 Lipoprotein(a). Statins only marginally affect Lp(a) plasma levels. Previous studies have reported either no effect on or an increase of Lp(a) levels after statin treatment.202,203 The mechanisms by which statins raise oxidized phospholipids on Lp(a) require further investigation. Downloaded from academic.oup.com/eurheartj/article/41/1/111/5556353 by guest on 07 October 2026