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4.6.4.4 Chronic kidney disease Patients with CKD are at high or very high risk of ASCVD, and have a characteristic dyslipidaemia (high triglycerides, normal LDL-C, and low HDL-C). Statin therapy or statin therapy in combination with ezetimibe (which allows larger LDL-C reductions without increasing the statin dose) has a beneficial effect on ASCVD outcomes in CKD.543 For patients with end-stage renal disease, however, we recommend that hypolipidaemic therapy should not be initiated (see Recommendations below). If patients with CKD already on a hypolipidaemic therapy enter end-stage renal disease, the therapy may be maintained.

4.6.4.5 Familial Hypercholesterolaemia Patients who could have genetic dyslipidaemias, such as heterozygous FH, can be identified by extreme lipid abnormalities and/or family history (Table 11). An LDL-C >4.9 mmol/L (190 mg/dL) in therapynaı ̈ve patients requires careful evaluation for possible FH. However, in the presence of premature ASCVD or family history, possible FH should be considered at lower LDL-C levels. Besides genetic testing (not always affordable), use of the Dutch Clinical Lipid Network criteria (Table 11) is recommended to identify possible FH. Homozygous FH is rare and should always be placed under the care of lipid experts. Treatment guidelines for people with FH can be found in the 2019 ESC/EAS dyslipidaemia Guidelines.3

4.7 Blood pressure

Hypertension is one of the most important preventable causes of premature morbidity and mortality. It affects more than 150 million

In patients with type 2 DM >40 years at high risk, lipid-lowering treatment with an ultimate LDL-C goal of >_50% LDL-C reduction and an LDL-C of <1.8 mmol/L (70 mg/dL) is recommended.540,541 I A Statin therapy may be considered in persons aged <_40 years with type 1 or type 2 DM with evidence of TOD and/or an LDL-C level >2.6 mmol/L (100 mg/dL), as long as pregnancy is not being planned. IIb C If the LDL-C goal is not reached, statin combination with ezetimibe should be considered.515,542 IIa B

ASCVD = atherosclerotic cardiovascular disease; DM = diabetes mellitus; eGFR = estimated glomerular filtration rate; LDL-C = low-density lipoprotein cholesterol; TOD = target organ damage. aClass of recommendation. bLevel of evidence. cSevere TOD in this specific context includes eGFR <45 mL/min/1.73 m2; eGFR 4679 mL/min/1.73 m2 plus microalbuminuria; proteinuria; presence of microvascular disease in at least three different sites (e.g. albuminuria plus retinopathy plus neuropathy). See Table 4 for details. dA stepwise approach to LDL-C targets is recommended; see section 3.2.3.1 and Figure 8. Adapted from 3

Recommendations for lipid management in patients with moderate-to-severe chronic kidney disease (Kidney Disease Outcomes Quality Initiative stages 35).

Recommendations Classa Levelb

The use of statins or statin/ezetimibe combination is recommended in patients with non-dialysis-dependent, stage 35 CKD.525,544,545 I A In patients already on statins, ezetimibe, or a statin/ezetimibe combination at the time of dialysis initiation, continuation of these drugs should be considered, particularly in patients with ASCVD. IIa C In patients with dialysis-dependent CKD who are free of ASCVD, commencing statin therapy is not recommended.546,547 III A

ASCVD = atherosclerotic cardiovascular disease; CKD = chronic kidney disease. aClass of recommendation. bLevel of evidence. Adapted from 3 Table 11 Dutch Lipid Clinic Network diagnostic criteria for familial hypercholesterolaemia

Criteria (choose only one score per group, the highest applicable; diagnosis is based on the total number of points obtained) Points 1) Family history First-degree relative with known premature (men aged <55 years; women <60 years) coronary or vascular disease, or first-degree relative with known LDL-C above the 95th percentile

1 First-degree relative with tendinous xanthomata and/or

arcus cornealis, or children aged <18 years with LDL-C above the 95th percentile

2 2) Clinical history

Patient with premature (men aged <55 years; women <60 years) CAD

2 Patient with premature (men aged <55 years; women

<60 years) cerebral or peripheral vascular disease

1 3) Physical examination

Tendinous xanthomata 6 Arcus cornealis before age 45 years 4 4) LDL-C levels (without treatment) LDL-C >_8.5 mmol/L (326 mg/dL) 8 LDL-C 6.58.4 mmol/L (251325 mg/dL) 5 LDL-C 5.06.4 mmol/L (191250 mg/dL) 3 LDL-C 4.04.9 mmol/L (155190 mg/dL) 1 5) DNA analysis Functional mutation in the LDLR, apolipoprotein B, or PCSK9 genes

8 A ‘definite’ FH diagnosis requires >8 points

A ‘probable’ FH diagnosis requires 68 points A ‘possible’ FH diagnosis requires 35 points CAD = coronary artery disease; DNA = deoxyribonucleic acid; FH = familial hypercholesterolaemia; LDL-C = low-density lipoprotein cholesterol; LDLR = low-density lipoprotein receptor; PCSK9 = proprotein convertase subtilisin/kexin type 9.

ESC 2021 ESC 2021 ESC 2021

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