p.42 抽出テキスト

..................................................................................................... undertaken. Restriction of calories and fat content (1015% recommended) in the diet, and alcohol abstinence are obligatory. Fibrate therapy (fenofibrate) should be initiated, with n-3 fatty acids (24 g/day) as adjunct therapy. Lomitapide may also be considered in severe cases.37 In patients with DM, insulin therapy should be initiated to achieve good glycaemic control. In general, a sharp decrease of TG values is seen within 25 days. In the acute setting, plasmapheresis is able to rapidly lower TG levels.384 Volanesorsen has been recently approved by the EMA as an adjunct to diet in adult patients with genetically confirmed FCS who are at high-risk for pancreatitis.

9.1.5 Other genetic disorders of lipoprotein metabolism Sometimes patients are encountered with extremely low levels of LDL-C or HDL-C. The most common form of genetic hypolipidaemia is hypobetalipoproteinaemia, which is dominantly inherited and often due to truncation of ApoB. Serum LDL-C is typically between 0.51.5 mmol/L (2060 mg/dL). A more profound deficiency of ApoB occurs in abetalipoproteinaemia when steatorrhoea, and neurological or other complications require specialist treatment. Almost absent levels of HDL-C occur in Tangier disease (analphalipoproteinaemia) and very low levels of HDL-C occur in lecithin cholesterol acyltransferase (LCAT) deficiency. Both these conditions are associated with distinct clinical syndromes and require specialist investigation. Very high levels of HDL-C are detected in patients with CETP deficiency. In the heterozygous form, levels of 2.02.3 mmol/L (8090 mg/dL) are typically observed, and levels >_5 mmol/L (>_200 mg/dL) are observed in homozygotes. This is not associated with atherosclerotic disease and may be associated with reduced risk. Lysosomal acid lipase deficiency or cholesterol ester storage disease (in children with Wolman disease) is a rare cause (recessive transmission) of elevated LDL-C and low HDL-C, accompanied by hepatomegaly and microvesicular hepatosteatosis. Statin treatment does decrease LDL-C levels and could therefore prevent ASCVD in these patients, but it cannot stop the progression of liver damage. Treatment with a PCSK9 inhibitor may lead to an even greater overload of lysosomes.385 Enzyme replacement therapy with sebelipase alfa might offer a treatment solution in the near future.386

9.2 Women

Few randomized trials of statin therapy have reported independently significant CV benefits in women,387,389 chiefly because women have not been adequately represented in statin trials.

9.2.1 Effects of statins in primary and secondary prevention There has previously been controversy over whether statins are effective for primary prevention in women. Using published data, a 2013 Cochrane analysis showed that statin therapy reduced all-cause mortality, vascular events, and revascularizations in primary prevention, and the proportional effects in women were similar to those in men.213 The CTT collaboration has provided a more complete assessment of the evidence through a comprehensive analysis of IPD from 22 trials of statins vs. control and five trials of more- vs. lessintensive statin therapy.35 Overall, 46 675 (27%) of 174 149 participants were women, and after adjustment for non-gender differences, the proportional reductions per mmol/L reduction in LDL-C in major vascular events, major coronary events, coronary revascularization, and stroke were similar in women and men.35

9.2.2 Non-statin lipid-lowering drugs Definitive evidence of the cardioprotective effects of non-statin drugs that lower LDL-C is now available, and the beneficial effects are similar in both women and men. In the IMPROVE-IT study,33 the relative benefit of adding ezetimibe to simvastatin was similar in women and men.33 In the ACCORD lipid study, there was no evidence that fenofibrate added to the effects of simvastatin in patients with T2DM,306 but an analysis of the FIELD study showed consistent CV event reduction in both women and men.389 Several outcome trials assessing the effects of adding a PCSK9 inhibitor to high-intensity statin therapy have now been reported, with similar proportional reductions in major vascular events in women and men.120,286,290

9.2.3 Hormone therapy Currently prescribed third-generation, low-dose oestrogenprogestin oral contraceptives do not appear to increase adverse coronary events390 and can be used, after baseline lipid profile assessment, in women with acceptable TC levels. In contrast, alternative contraceptive measures should be recommended in women with hypercholesterolaemia [LDL-C >4 mmol/L (>160 mg/dL)] or with multiple risk factors, and in those at high-risk of thrombotic events.391 Oestrogen replacement therapy, despite some favourable effects on lipid profiles, has not been demonstrated to reduce CV risk and cannot be recommended for CVD prevention in women.392 No lipid-lowering drugs should be administered during pregnancy and the period of breastfeeding because data on possible adverse effects are lacking. However, bile acid sequestrants may be considered. Box 6 lists the main measures in the management of dyslipidaemia in women.

9.3 Older people

The proportion of older people (defined herein as those aged >65 years) in society is increasing and, as a consequence, >80% of individuals who die from CVD are >65 years of age. The proportion of patients with MI >85 years of age has increased several-fold.393 A meta-analysis of observational studies has shown that higher TC is associated with increased CAD mortality at all ages.62,394 However, since the absolute risk of CAD is higher in older persons,

Box 6 Management of dyslipidaemia in women

Statin treatment is recommended for primary prevention of ASCVD in high-risk women.34,35 Statins are recommended for secondary prevention in women with the same indications and goals as in men.34,35 Lipid-lowering drugs should not be given when pregnancy is planned, during pregnancy, or during the breastfeeding period. However, for severe FH patients, bile acid sequestrants (which are not absorbed) and/or LDL apheresis may be considered. ASCVD = atherosclerotic cardiovascular disease; FH = familial hypercholesterolaemia; LDL = low-density lipoprotein. Downloaded from academic.oup.com/eurheartj/article/41/1/111/5556353 by guest on 07 October 2026