Refractory hyperlipidemia combined multiple large blood vessel disease
51 years old， male
Chief complaint: Bilateral lower limbs ache for more than two years， aggravated for 1month
Present history:
Patient complained of bilateral lower limbs ache since two years ago， which was brought by walking 10 minutes， relieved after 1 or 2 minutes rest， not associated with edema， flare or darkening. Nine months ago， he was admitted in our hospital for dizziness and poor activity of right upper limb， diagnosed as the subacute cerebral infarction. Ultrasound showed arteriosclerosis occlusion of lower extremity. After few weeks of medicine such as Clopidogrel， Lipitor and Fenofibrate etc， he was discharged and intermittently took the lipid-lowering therapy. Since 1 month ago， patient felt the intensified pain of the bilateral lower limbs after walking， along with colder skin， muscle atrophy and paresthesia. Ultrasound showed the severe stenosis and occlusion of multiple blood vessels. He was admitted to our department for further therapy.
Past medical history:
1）Mixed hyperlipidemia for more than 10 years， the highest level of TG was 32 mmol/L， TC was16.9 mmol/L. He discontinued the Rosuvastatin because of the elevated liver enzymes. Through medicine treatment (Lipitor + Fenofibrate+ Policosanol) for 3 weeks， TG was decreased to 5.97 mmol/L; LDL-C was decreased to 2.34 mmol/L. Genetic test showed no known gene mutations of familial hypercholesterolemia.
2) Acute pancreatitis induced by drinking in 1999， with conservative treatment and no relapse for 5 years.
3) Type 2 diabetes mellitus for16 years: insulin glargine 32IU Qn ih， Acarbose 100mg Tid po and Glucophage 0.5 Tid po. FBG was 8-11mmol/L， PBG was 14-15mmol/L， HbA1c was decreased from 10.4% to 9.2%.
4) Diabetic nephropathy for 4 years. CCr was 130-150mmol/L.
5) Old cerebral infarction for 9 months with multiple intracranial vascular stenosis.
6）2 years ago， coronary CTA showed triple vessel disease and coronary angiography showed that LAD stenosis of 50-60%; LCX stenosis of 50%; RCA stenosis of 80% with severe diffuse calcification. Stressed ECT showed no evidence of ischemia 9 months ago.
7) Clopidogrel genotype detection: positive， one homozygous mutation and one heterozygous mutation， slow metabolism type.
Personal history: Smoking for more than 20 years， 40 cigarettes per day， decreasing to 10 cigarettes per day for 1 month.
Family history: His father died of coronary heart disease. His mother has diabetes and mixed hyperlipidemia. His younger sister has diabetes， hyperlipidemia and hypertension.
Physical examination: BP 120/76mmHg， HR 90 bpm， No positive signs except muscle atrophy and paresthesia of bilateral lower limbs， and week pulse of the dorsalis pedis artery.
Auxiliary examination:
ECG: Sinus rhythm， normal.
UCG: Aortic valve calcification， decreased left ventricular diastolic function， EF was 68%.
Abdominal ultrasound: Mild to moderate fatty liver.
Carotid artery ultrasound: Bilateral carotid artery plaque.
Iliac artery ultrasound: Mild stenosis in the bifurcation of bilateral common iliac artery.
Bilateral lower limb artery ultrasound now (vs.9 months ago) :
Arteriosclerosis occlusion of bilateral lower extremity
Right side:
1)The superficial femoral artery stenosis of 80% at initial and middle segment. (vs. Occlusion at initial segmen and the branch stem formation 9 months ago.)
2) The deep femoral artery stenosis 70% at initial segment. (vs. 50% 9 months ago.)
3) The popliteal artery occlusion in proximal segment and stenosis less than 60% in middle and distal segment.
Left side:
1)The common femoral artery stenosis was less than 50%. (vs. 50% 9 months ago.)
2)The superficial femoral artery stenosis was 80-90% at proximal and middle segment. (vs. 50%- 60% 9 months ago.)
3) The deep femoral artery stenosis was 60% at middle segment. (vs. 60% 9 months ago.).
4) The popliteal artery severe stenosis of 80%.
Blood test: Hb 129 g/L; ALB 37.2 g/L; BUN 6.4 mmol/L， CCr 131 umol/L; TG 8.81 mmol/L， TC 7.26 mmol/L， HDL-C 0.68 mmol/L， LDL-C 2.23 mmol/L; FBG 5.77 mmol/L， HbA1c 9.2%; Urinaryprotein quantitatie: 2.5 g/ 24 h. HCY 26.7 umol/L
Primary diagnosis:
1.Arteriosclerosis Occlusion of bilateral lower extremity
2.Mixed hyperlipidemia
3.Diabetes (2 type)， Diabetic peripheral neuropathy， Diabetic nephropathy
4. Chronic renal disease (Stage 3)
5. Coronary heart disease
6. Old cerebral infarction
Treatment:
Ticagrelor:90mg Bid，
Lipitor20mg Qn +Fenofibrate0.2 Qn+ Ezetrol10mg Qd+ Policosanol 10mg Bid
Insulin glargine 32IU Qn ih + Acarbose 100mg ， Glucophage 0.5 Tid po
Ketosteril 3 pills Tid， Sulodexide:25mg Bid
Calcium dobesilate capsules 0.5 Tid， Methycobal1mg Qd im.， Folic acid: 5mg Qd
Pancreatic kininogenase enteric-coated tablets:240IU Tid， Alprostadil: 10ug Qd iv.gtt
Case Summary and Question for Answer
1.Patient has refractory hyperlipidemia， suspicious of familial hypercholesterolemia. Though using multi-lipid-lowering medicine， the level of the triglyceride was not well controlled and the reason for that was not known. Is there any better solution for author to resolve this problem?
2.Patient‘s antiplatelet therapy: Aspirin was stopped because of his renal insufficiency. Ticagrelor was used to finish the effective antiplatelet， took place of clopidogrel， because of the genotype test showed he was the slow metabolism type of it.
3.Is there a chance for patient to accept percutaneous interventional therapy for handling the severe stenosis of bilateral lower extremity?
Before the operation， we should complete a comprehensive preoperative risk assessment， especially kidney risk. Giving him the preoperative hydration therapy and estimating the dosage of contrast agent will reduced the kidney injury.
4. Patient was discharged from hospital after conservative medical treatment， what was the best discharged instruction for improving his prognosis?
Seth S. Martin， MD， MHS
Assistant Professor of Medicine and Cardiology
Ciccarone Center for the Prevention of Heart Disease
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I was asked to comment on this case from a lipidology perspective. My impression is that the patient most likely has a severe form of familial combined hyperlipidemia. It is a common genetic disorder that is present in an estimated 1 in 200 persons and 1 in 5 of those who develop premature CHD (as occurred in this case). Greater flux of fatty acids with elevated hepatic apoB secretion results in excess synthesis of cholesterol esters and triglycerides leading to a hyperTG hyperapoB phenotype. The condition is exacerbated by secondary factors such as type II diabetes mellitus， which is both present and poorly controlled here. Reducing saturated fats and simple carbohydrates in the diet， increasing aerobic physical activity， and achieving weight loss can have significant benefits. Unfortunately， from the standpoint of physical activity， it appears that the patient’s peripheral arterial disease is so advanced that it is now limiting his ability to obtain physical activity. It is not stated what the patient’s body mass index is and I would not be surprised if it is very high. If that is indeed the case that severe obesity is present， then gastric bypass surgery may be considered. Furthermore， it should be noted that nephrotic syndrome can exacerbate the hyperTG hyperapoB phenotype. The patient does not seem to formally meet criteria for nephrotic syndrome， but has a high urinary protein level and should be evaluated and treated by a nephrologist.
From a drug therapy standpoint， the patient is on an aggressive 4 drug regimen， but the history notes concern for adherence. The first priority is to improve adherence through clinician-patient discussion and perhaps use of medication pill boxes and calendar reminders. After addressing that fundamental issue， changes could be considered to the drug regimen， especially given the very high TG level is exposing him to excess risk of recurrent pancreatitis. For example， prescription strength omega-3-acid ethyl esters are not currently being used; they have strong triglyceride lowering effects and are well tolerated. Although the LDL cholesterol level is considerably better controlled than the TG level， it is noted that the LDL cholesterol level is not optimized either. The first priority is to carefully address lifestyle and medication adherence as described. At present， the patient remains at high residual risk for atherosclerosis progression and recurrent vascular events.