Supravalvular Aortic Stenosis with Extensive Atherosclerosis and Fatal Premature Coronary Artery Disease Secondary to Homozygous Familial Hypercholesterolemia – So Early But Too Late!!

Introduction: Heterozygous familial hypercholesterolemia (heFH) is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and increased risk for premature coronary artery disease (CAD) and death. Reduction of CAD and mortality by statins has not been properly quantified in heFH. The aim of the current study is to determine the effect of statins on CAD and mortality in heFH. Methods: All adult heFH patients identified by the Dutch FH screening program between 1994 and 2014 and registered in the PHARMO Database Network were eligible. Of these patients we obtained hospital, pharmacy (in- and outpatient), and mortality records in the period between 1995 and 2015. The effect of statins (time-varying) on CAD and all-cause mortality was determined using a Cox proportional hazard model, while correcting for the use of other lipid-lowering therapy, thrombocyte aggregation inhibitors, antihypertensive and antidiabetic medication (all time-varying). Furthermore, we used inverse probability for treatment weighting (IPTW) to account for differences between statin-treated and untreated patients regarding history of CAD before follow-up, age at start of follow-up and age of screening, as well as body mass index, LDL-C and triglycerides. Results: Of the 25,479 identified heFH patients, 11,021 gave informed consent to obtain their medical records, of whom 2,447 could be retrieved. We excluded 766 patients younger than 18. The remaining 1,681 heFH patients comprised our study population and these had very similar characteristics as compared to the 23,798 excluded FH patients, e.g. mean (SD) LDL-C levels were 214 (74) vs. 203 (77) mg/dL. Among 1,151 statin users, there were 133 CAD events and 15 deaths during 10,115 statin treated person-years, compared to 17 CAD events and 9 deaths during 4,965 person-years in 530 never statin users (combined rate: 14.6 vs. 5.2, respectively, p<0.001). After applying IPTW to account for indication bias and correcting for use of other medications, the hazard ratio of statin use for CAD and all-cause mortality was 0.61 (0.40 - 0.93). Conclusions: In heFH patients, statins lower the risk for CAD and mortality by 39%.

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Coronary artery disease in a child with homozygous familial hypercholesterolemia: Regression after liver transplantation

Journal of Clinical Lipidology ◽

10.1016/j.jacl.2019.09.007 ◽

2019 ◽

Vol 13 (6) ◽

pp. 880-886

Author(s):

Constance E. Cephus ◽

Athar M. Qureshi ◽

S. Kristen Sexson Tejtel ◽

Mahboob Alam ◽

Douglas S. Moodie

Keyword(s):

Coronary Artery Disease ◽

Liver Transplantation ◽

Coronary Artery ◽

Familial Hypercholesterolemia ◽

Homozygous Familial Hypercholesterolemia ◽

Artery Disease

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Clinical manifestations of familial hypercholesterolemia: a case series

International Journal of Advances in Medicine ◽

10.18203/2349-3933.ijam20212110 ◽

2021 ◽

Vol 8 (6) ◽

pp. 839

Author(s):

Subramani K. Shankar Rao ◽

Nagamani A. Chikkabasavaiah ◽

Varshit D. Hathi ◽

Santosh Jadhav ◽

Saleha Noorain ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Coronary Artery Bypass Grafting ◽

Aortic Stenosis ◽

Familial Hypercholesterolemia ◽

Coronary Artery Bypass ◽

Artery Bypass ◽

Bypass Grafting ◽

Life Threatening ◽

Artery Disease

Familial hypercholesterolemia is a rare, monogenic, co-dominant, life-threatening disorder resulting from loss of function mutations in the genes responsible for synthesis of low-density lipoprotein receptors or apo-B genes or gain of function mutations in PCSK9 genes in the liver which affects 0.2% of the population. It is characterized by severe lifelong elevation of LDL cholesterol and by development of xanthelasma, xanthomas, premature coronary artery disease and peripheral artery occlusive disease. Most patients develop PCAD and aortic stenosis before the age of 20 years and die before 30 years of age. The diagnosis of FH is usually based on clinical presentation and commonly used criteria are the Dutch lipid clinic network criteria, Simon Broome criteria or the WHO criteria. We encountered four cases of familial hypercholesterolemia over last 10 years. All the four patients presented with effort angina and all were found to have obstructive coronary artery disease oncoronary angiogram and two of them had severe supravalvular aortic stenosis. All four patients were on dietary modifications, high intensity statin and cholesterol absorption inhibitor. Two patients underwent coronary artery bypass grafting with aortoplasty, one patient underwent coronary artery bypass grafting and one patient underwent percutaneous transluminal coronary angioplasty. Familial hypercholesterolemia leads to development of life-threatening manifestations early in the second and third decades of life. Early diagnosis, aggressive treatment and control of risk factors and cascade screening are important in management and will help to reduce the morbidity and mortality associated with this disease.

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