Case #357: Family Ties: FHx +LDL = HeFH
“Marcus,” a 33-year-old male, visited our office for a complete physical in April 2010. The patient appeared healthy and was fit and active. His social history includes being an occasional smoker and occasional alcohol user.
The patient’s CPE was normal except for being overweight and included:
- Height = 68.5
- Weight = 215
- BMI = 32
- BP = 120/70
- HR = 64
Marcus’ family history was troubling, with significant cardiovascular problems. His father suffered and survived a stroke at age 62. His maternal grandfather died of a heart attack in his 40s, and his paternal grandmother had heart problems and required a pacemaker. Both Marcus and his father had a history of high cholesterol as evidenced by previous lab work. Additionally, Marcus said he has an aunt with diabetes, and his father, grandmother and grandfather all have high blood pressure.
The patient exhibits one of five NCEP risk factors, placing him in the low-risk category. Admittedly, his family history is strong, but doesn’t meet premature risk criteria. HDLc is borderline at 40, but it has to be under 40 to be a risk factor per criteria. Framingham Risk Scoring doesn’t apply here due to low risk per NCEP.
To get the whole story on Marcus, including possible hypercholesterolemia, I decided to run a VAP Lipid Panel. This would give me a detailed look at his directly measured LDLc plus NHDLc, apoB and RLPs, and other subfractions.
Marcus’ initial VAP Lipid Panel results from April 2010 (no medication) definitely presented us with some challenges, with high total cholesterol (313) and triglycerides (213). Directly measured LDLc was 232 and NHDLc was at 273. HDLc, as noted above, was borderline low at 40. ApoB was high (bad) at 180 with his apoB/A1 ratio high (bad) at 1.33. Lp(a)-c was zero but RLPs were high (bad) at 38. Vitamin D was low at 12.6, so we started him on OTC replacement.
Based on persistently high cholesterol and family history, including very early heart attack, the patient was diagnosed with heterozygous familial hypercholesterolemia (HeFH) genetic disorder. I discussed with Marcus, and he insisted on working on TLC prior to drug therapy, despite guidelines suggesting pharmacoptherapy with LDLc above 190 mg/dL.
Although Marcus did not meet the appropriate use criteria, he chose to obtain a CUS/CIMT in May 2010 due to his history of tobacco use, high cholesterol and family history. However, the procedure is inexpensive in our area and easy to do. His CIMT composite score showed 0.655 mm (patient age = 33; arterial age = 49) with no prior lipid therapy. No plaque was noted.
Lipid therapy was started in October 2010. A repeat CIMT in May 2011 showed a mean score 0.648 mm with no plaque, so his score was not increasing.
Click to view Marcus’ VAP Lipid Panel results and appropriate reference ranges from Atherotech:
|Standard Lipid Panel||April 2010||September 2010||February 2011||June 2011||May 2012|
|LDL||(see VAP Lipid Panel)||(see VAP Lipid Panel)||(see VAP Lipid Panel)||(see VAP Lipid Panel)||(see VAP Lipid Panel)|
|Medications||None||Vitamin D||Vitamin D; fenofibrate, rosuvastatin = 20 mg||Vitamin D; fenofibrate, rosuvastatin = 20 mg||Vitamin D; fenofibrate, rosuvastatin = 20 mg; ezetimibe 10 mg|
|VAP Lipid Panel|
|Total LDL (Direct)||232||200||159||151||140|
|Remnant Lipoproteins(IDL + VLDL3)||38||38||34||17||23|
|• ApoB/A1 Ratio||1.33||1.17||0.93||0.74||0.81|
|Other Atherotech Tests|
|Urea Nitrogen (BUN)||13.7||18.2||13.3|
After trying the TLC approach, repeat labs in September 2010 showed TC had dropped somewhat to 291, but the patient’s RLPs remained at 38 and trigs were now 471. Other readings of note included:
- DLDLc = 200
- NHDLc = 250
- ApoB = 169
- HDL = 41
- RLP = 38 (still bad!)
- Density pattern remain B
Marcus’ vitamin D was up to 21.1; improving but still low, so we increased his OTC dose. And since we didn’t see much improvement in lipids with TLC, the patient agreed to more aggressive therapy. He was started on fenofibrate and rosuvastatin 20 mg. His repeat labs in February 2011 started to show some improvement, with TC dropping to 247 trigs down to 290 and RLPs down a few ticks to 34. The patient’s LpPLA2 as measured by the PLAC Test was 131.19 (good, optimal values are under 200).
By the time we ran June 2011 labs (on same meds), we were getting much closer to reaching our TC goal of under 200 and trigs were down to 107 with improvements pretty much across the board, including RLPs now at 17. Other lipids of note included:
- FLDLc = 151
- NHDLc = 169
- ApoB = 117 (LDL, NHDL and apoB goals are under 160, 190, 120 respectively, based on patient’s risk status)
- HDLc = 55
- ApoA1 = 159, Ratio = 0.74 (these are pretty impressive changes, and quitting smoking likely helped)
Ezetimibe 10 mg was added, and Marcus’ May 2012 VAP reflected a further drop in TC to 216 and LDL to 140. RLPs remained under control at 23 (recommended is under 30 mg/dL). We have encouraged better compliance with OTC vitamin D therapy as well.
Although relatively uncommon, occurring in about one in 500 people, HeFH is a serious genetic condition that confers a much greater risk of early heart disease than the general population. FH typically requires aggressive lipid-lowering drug therapy, including statin therapy.
FH risk factors include having parents with total cholesterol levels greater than 300, or having a parent or grandparent who had symptomatic heart disease at age 55 or younger. If left untreated, individuals with HeFH often develop heart disease in their 40s and 50s. Homozygous FH, while much rarer, usually results in CV events at even younger ages. Studies have also identified a higher prevalence of FH within certain ethnic groups: Chinese Canadians, French Canadians, Finns, Dutch, Icelanders, Lebanese Christians, Lithuanian Jews and South African Afrikaners.
In this case, detailed lipid profiling with the VAP Lipid Panel helped to diagnose HeFH as well as residual lipid defects. It also helped me develop an aggressive, effective management and treatment plan for CVD risk reduction. Marcus did not initially want to undertake drug therapy, even though guidelines would suggest we treat any LDLc over 190. However, after getting a detailed look — through comprehensive testing — at the lack of significant improvement following TLC, he agreed to add statin therapy.
Note the dramatic improvement in the patient’s May 2012 labs — RLPs, DLDLc, NHDLc, apoB, HDL, HDL3, apoA1, apoB/apoA1 ratio — with medication, tobacco cessation and lifestyle dietary management. Based on this data, we would like to have his DLDLc, NHDLc and apoB closer to 100-130, 130-160 and 90-100, respectively. After discussion about raising rosuvastatin to 40 mg or changing to atorvastatin 80 mg or simvastatin 40/ezetimibe 10 mg or adding ezetimibe 10 mg or adding colesevelam 3.6 grams, the patient opted for the addition of ezetimibe to his current treatment. I do think ER Nicotinic Acid is an excellent option as well based on his VAP lab values. We will repeat VAP and CMP in three to five months.
In Patient Terms
Following the FH diagnosis, I recommended that Marcus encourage all family members to be tested through their PCP. I have also had several discussions with Marcus about the critical importance of diet, exercise and quitting smoking in dealing with this condition. Patients with HeFH are at greatly increased risk of heart disease. Poor diet, lack of exercise and smoking makes the risk exponentially higher.
I told Marcus I was very pleased with his progress. His LDLc levels were the best we have ever seen them, and there have been great improvements in much of his lipid profile. I counseled Marcus that with continued close management and TLC, we could keep his CVD risk low.
ASA = Acetylsalicylic Acid = Aspirin
BMI = Body Mass Index
CIMT = Carotid Intimal-Media Thickness
CVD = Cardiovascular Disease
CMP = Cardiometabolic Metabolic Panel
CUS/CIMT = Carotid Ultrasound/ Carotid Intimal-Media Thickness
CPE = Complete Physical Exam
FLDLc = Framingham LDLc
FHx = Family History
HDLc = High Density Lipoprotein Cholesterol
HeFH = Heterozygous Familial Hypercholesterolemia
IDLc = Intermediate Density Lipoprotein Cholesterol
LDLc = Low Density Lipoprotein Cholesterol
Lp-PLA2 = Lipoprotein-associated phospholipase A2, The PLAC Test.
NCEP = National Cholesterol Education Program
NHDLc = Non-HDL Cholesterol
OTC = Over The Counter
RLP = Remnant Lipoprotein
TC = Total Cholesterol
TLC = Therapeutic Lifestyle Changes
TG = Triglycerides
VAP = Vertical Auto Profile (VAP) Lipid Panel