Refractory hyperlipidemia combined multiple large blood vessel disease

　　Seth S. Martin， MD， MHS

　　Assistant Professor of Medicine and Cardiology

　　Ciccarone Center for the Prevention of Heart Disease

　　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.