One article mastered the management of "dyslipidemia in the elderly", and the "Chinese Expert Consensus on the Management of Dyslipidemia in the Elderly" was released!

Atherosclerotic cardiovascular disease (ASCVD) is the main cause of death and disability in the elderly, and the prevalence and mortality rate increase
with age.
Dyslipidemia is an independent risk factor for ASCVD and cardiovascular events, and there is substantial evidence that statins delay the onset and progression of ASCVD and reduce the risk of
cardiovascular events and death.
However, due to concerns about drug safety, the elderly population has insufficient medication and a high
discontinuation rate.

In order to promote the prevention and treatment of ASCVD in the elderly in China, the "Chinese Expert Consensus on the Management of Dyslipidemia in the Elderly" was recently released in the Chinese Journal of Internal Medicine, and clinical management suggestions
were put forward for the management of dyslipidemia in the elderly in China.

Recommendations for the management of dyslipidemia in older Chinese adults

(1) Lifestyle therapy

Maintaining a healthy lifestyle is a basic measure
to treat dyslipidemia in the elderly.

➤ It mainly includes smoking cessation, alcohol restriction, balanced diet, reducing saturated fatty acid and cholesterol intake, increasing the intake
of vegetables, fruits, fish, legumes, whole grains, nuts and foods rich in plant sterols and fiber.

➤ It is not recommended that the elderly control their diet and lose weight
too strictly.

➤It is recommended that the elderly adhere to regular aerobic exercise, and should pay attention to avoid injuries and falls caused by exercise when exercising, and those who have the conditions can choose an exercise program
under the evaluation and guidance of a sports rehabilitation specialist.

(2) Lipid adjustment treatment goals and recommended drugs

1.
It is recommended that elderly patients with ASCVD actively use statins, and for elderly people at risk of cardiovascular disease, blood lipid management goals
are formulated according to cardiovascular disease risk stratification.

Table 1 Target values of lipid-regulating therapy for the elderly [mmol/L (mg/dl)]

2.
Statins
are recommended for elderly patients with ASCVD and elderly people with multiple cardiovascular risk factors ≤ 75 years old.

3.
For the elderly aged > 75 years old with high cardiovascular risk, a comprehensive assessment of life expectancy, frailty, comorbid diseases, liver and kidney function, economic factors and other factors should be carried out, and the benefit-risk ratio, drug interactions, adverse reactions and personal willingness of lipid-modifying therapy should be weighed to decide whether to use low- and medium-dose statins
.

4.
When the elderly do not meet the standard of tolerable dose statin LDL-C, ezetimibe or PCSK9 inhibitors
can be added.

5.
When TG is elevated, secondary factors should first be excluded or corrected and lifestyle interventions
should be carried out.
For ASCVD patients or very high-risk elderly people, when non-HDL-C does not meet the standard or TG continues to rise (2.
3~5.
6 mmol/L) after statin therapy, fibrates or fish oil preparations can be combined with fibrates (high-purity EPA is preferred).

Fasting TG ≥ 5.
6 mmol/L, TG should be lowered first, and fibrates and fish oil preparations (high-purity EPA is preferred) are
preferred.

(3) Monitoring of dyslipidemia treatment in the elderly

➤ The elderly who first undergo lifestyle treatment should have their blood lipid levels reviewed in 6~8 weeks, and those who meet the standard should continue to adhere to a healthy lifestyle and be rechecked for 3~6 months; If the standard is continuously met, it will be rechecked
every 6~12 months.

➤ Review blood lipids, muscle enzymes and liver and kidney function 4 weeks before and after taking statins, and monitor for adverse reactions such as myalgia, fatigue and digestive tract symptoms when taking the drug, and long-term use should be followed up regularly
.
Patients who develop muscle or digestive symptoms after taking statins should have muscle enzymes and liver function
monitored.

➤If the increase in blood creatine kinase (CK) does not exceed 4 times the upper limit of normal and the muscle symptoms are mild, or the elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) does not exceed 3 times the upper limit of normal, statins can be continued and re-examined
.

➤ If the blood CK is elevated more than 4 times the upper limit of normal or ALT, AST is more than 3 times the upper limit of normal and bilirubin is elevated, the dose of statins should be stopped or reduced, and the benefits/risks of statins should be evaluated again after returning to normal, and whether to continue taking statins or switch to other lipid-modifying drugs; If you need to continue to use lipid-modifying drugs, you can change the type or reduce the dose and observe
closely.

➤ If CK is elevated more than 10 times the upper limit of normal, statins should be stopped immediately and admitted to the hospital for hydration therapy
.
If the standard is not met for 3~6 months, the dose or type of statin should be adjusted, and ezetimibe or PCSK9 inhibitors should be added if necessary, and rechecked
every 6~12 months after reaching the standard.

Commonly used lipid-modifying drugs and their safety

(1) Statins

1.
Pharmacological properties: currently commonly used statins, lovastatin, simvastatin, fluvastatin, atorvastatin and pitavastatin are lipophilic statins, pravastatin and rosuvastatin are hydrophilic statins (see Table 2 for details
).

Blood lipid kang is fermented and refined by inoculation of japonica rice with red yeast, containing 13 statin homologs such as lovastatin, unsaturated fatty acids, sterols and a small amount of flavonoids
.
The usual dose is 1.
2 g/day (0.
6 g twice daily) including lovastatin 10 mg
.

Lovastatin and simvastatin are more easily absorbed when taken with food, rosuvastatin, atorvastatin, fluvastatin and pitavastatin are not affected by food, and pravastatin is taken with food to reduce absorption
.
Since the synthesis of cholesterol in the liver peaks at night, fluvastatin, lovastatin, simvastatin have a short half-life, it is recommended to take it at night; Atorvastatin, pitavastatin, and rosuvastatin have a long half-life and can be taken
at any time.
The reduction in LDL-C by statin therapy is shown in Table 3
.

Table 2 Pharmacological properties of statins

Table 3 Statins reduce the amplitude and dose of LDL-C

2.
Safety: Although the safety and tolerability of statins in the elderly are good, relevant adverse reactions
should be identified and treated in time.
In general, the adverse effects of statins increase with increasing dose, and common adverse effects include abnormal liver function, muscle damage, CKD, and newly diagnosed diabetes
.

(2) Non-statin lipid-modifying drugs

1.
Cholesterol absorption inhibitor: ezetimibe inhibits the absorption of cholesterol in the intestine by inhibiting the cholesterol transporter NPC1L1, reducing LDL-C by 15%~22%, and the usual dose is 5~10 mg/d
.

Medication attention: ezetimibe is safe and well tolerated, and common adverse reactions such as headache, abdominal pain, diarrhea, bloating, fatigue and liver enzyme abnormalities
.

2.
PCSK9 inhibitors: PCSK9 inhibitors prevent PCSK9-mediated LDLR degradation by inhibiting the binding of PCSK9 to low-density lipoprotein (LDLR) receptors (LDLR) in circulation, promote LDL-C clearance, reduce LDL-C by an average of 60%, and reduce cardiovascular events
.
The usual dose of elolumab is 140 mg/2 weeks or 420 mg/4 weeks, and the usual dose of alicidumab is 75~150 mg/2 weeks
.

Caution: Common adverse reactions are injection site discomfort, allergic reactions, and flu-like symptoms
.

3.
Fibrates: fibrates reduce TG, increase HDL-C, and reduce TG by activating peroxisome proliferators α activating receptor and lipoprotein lipase, and reducing TG by 20%~50
%.
Commonly used fenofibrate, usual dose 200 mg/day
.

Medication attention: common adverse reactions such as myopathy, elevated aminotransferases, gastrointestinal reactions and rash can lead to increased serum creatinine and decreased eGFR, which are usually reversible, and the dose
should be adjusted when using CKD patients.
Geferozil in combination with statins increases the risk of myopathy, and the risk of myopathy in fenofibrate is significantly reduced
.

4.
Niacin: Niacin reduces the secretion of very low density lipoprotein (VLDL) by inhibiting diacylglyceryl transferase-2, reducing TG by 15%~25%, and clinical studies have not shown the cardiovascular benefits
of niacin.

Medication attention: adverse reactions include facial flushing, gastrointestinal symptoms, liver damage, elevated uric acid and blood sugar
.
Contraindicated in patients with severe or unexplained liver damage, alcoholism, active peptic ulcer and gout
.
Adverse effects increase
when niacin is combined with statins.

5.
Fish oil preparation (n-3 PUFA): fish oil preparation 3~6 g/d reduces TG by 30%~50
%.
The efficacy of n-3 PUFA was related to the baseline TG level, dose and type, and reduced TG by 30%~60% in severely elevated TG and 15%~30% in mildly and moderately elevated TG
.
High-purity EPA reduces cardiovascular events
in patients at high risk of cardiovascular disease.

Medication attention: Common adverse reactions of fish oil preparations are belching, nausea, fishy smell, etc.
, and large doses of fish oil may increase the risk of
atrial fibrillation.

(3) Drug interactions

Elderly people often use a combination of drugs, and drug interactions and adverse reactions
need to be concerned.
When combined with drugs metabolized by the CYP450 enzyme and affecting P-glycoprotein (P-gp), the risk of adverse statin reactions increases
.
Inhibitors increase statin plasma concentrations by competing for binding sites or reducing enzyme and protein activity by increasing statin bioavailability or reducing statin clearance, and inducers increasing CYP450 enzyme or P-gp activity accelerate statin metabolism and reduce statin blood concentration
.

Table 4 CYP450 enzyme and P-glycoprotein inhibitors and inducers affecting statin metabolism

Statins combined with niacin or fibrates increase the risk of
myopathy.
Bioavailability increases
when ezetimibe is combined with fibrates or cyclosporine.
Fibrates in combination with warfarin increase anticoagulant efficacy and bleeding risk, and in combination with immunosuppressants can lead to deterioration
of renal function.

Precautions for lipid adjustment therapy in the elderly

1.
It is recommended to fully evaluate the benefits/risks of lipid-modifying therapy in the elderly and select drugs
according to individual characteristics.
For the elderly over 75 years old, according to biological age, cardiovascular risk stratification, liver and kidney function, concomitant diseases, combined medication, nutritional status, frailty state, life expectancy, etc.
, after weighing the pros and cons, determine whether to use lipid-modifying drugs, and it is not recommended to use lipid-regulating drugs for the elderly who are weak or have limited life expectancy
.

2.
With age, physiological changes in the elderly lead to muscle atrophy and weakening of muscle strength, and lipid-modifying drugs can cause or aggravate muscle symptoms, affect quality of life and increase the risk of
falls.
Older adults who are female, small, CKD, perioperative, hypovolaemia, severe infection, and thyroid dysfunction are at
increased risk of myopathy.

3.
The adverse reactions of statins increase with the increase of dose, and most elderly people can achieve LDL-C with medium and small doses of statins; Dose should be started with small or moderate doses and adjusted according to efficacy, with statin intolerance tapering or switching to a different type of statin; When a tolerable dose of statin LDL-C is not met, ezetimibe or PCSK9 inhibitors
may be added.
Older people with rapidly decreasing TC or LDL-C after taking low-dose statins should be investigated for tumors and other wasting diseases
.

4
.
When the elderly have decreased liver and kidney function and combine multiple drugs, drug interactions and adverse reactions are prone to occur, and drugs with different metabolic pathways in the body should be selected.
When statins are combined with other lipid-modifying drugs, they can increase the risk of liver and muscle damage, and it is necessary to pay attention to the individual characteristics and tolerance of the elderly, avoid high-dose combinations, and monitor drug interactions and adverse reactions
.

5
.
Lipid-regulating drugs should be used for a long time, and should not be discontinued without special reasons.
After stopping the drug, blood lipids increased or even rebounded, which significantly increased cardiovascular events and mortality
.

brief summary

In short, lipid-regulating therapy is an important measure
for the prevention and treatment of ASCVD in the elderly.
LDL-C is the primary treatment target, and non-HDL-C is the secondary target
.
A healthy lifestyle is a basic measure for the treatment of dyslipidemia in the elderly, and statins are the preferred lipid-modifying drugs
.
It is recommended to fully evaluate the pros and cons of lipid-modifying therapy, and reasonably select lipid-modifying drugs
according to the risk stratification of cardiovascular disease in the elderly and individual characteristics.
Low- and medium-dose statins are recommended for older people, and ezetimibe or/and PCSK9 inhibitors
can be added when LDL-C at tolerable doses is not met.
When LDL-C is met and TG is elevated in ASCVD or very high-risk elderly patients, fibrates or/and fish oil preparations (high-purity EPA is preferred).

Consensus link: http://rs.
yiigle.
com/CN112138202210/1427838.
htm

References: Liu Meilin, Zhang Yumeng, Fu Zhifang, et al.
Chinese expert consensus on dyslipidemia management in the elderly[J].
Chinese Journal of Internal Medicine, 2022, 61(10) : 1095-1118.
) DOI: 10.
3760/cma.
j.
cn112138-20220407-11251.