One baby is born with familial hypercholesterolemia every minute. FH is underdiagnosed and undertreated globally. Familial hypercholesterolemia (FH) is an inherited condition leading to severely elevated serum low density lipoprotein cholesterol (LDL-C) that leads to premature atherosclerotic cardiovascular disease (ASCVD) and accounts for 2–3% of the cases of myocardial infarction in patients aged less than 60 years.
It is caused by mutations in the genes of the LDL-R (LDL receptor), Apo B (Apolipoprotein B) or PCSK-9 (Proprotein convertase subtilisin/kexin type 9) that interfere with clearance of LDL-C by the liver.
The contribution of FH to premature cardiovascular disease in India is still unknown. The heterozygous familial hypercholesterolemia (HeFH) phenotype is encountered most often (1 in 250-500) whilst the rarely encountered homozygous familial hypercholesterolemia (HoFH) phenotype has a worse prognosis (1 in million). Considering the Indian population of over a 1.32 billion, approximately 2.6 million cases of HeFH and 2500 cases of HoFH are estimated to be present. Most of these patients are undiagnosed or undetected and are responsible for premature coronary artery disease in India.
HeFH is seen when the individual inherits one mutant gene and is characterized by a 3–4-fold higher LDL-C concentration. Lipid stigmata including corneal arcus and tendon xanthomata can be seen in HeFH patients, and patients generally develop premature cardiovascular disease during their forties. The patients with HoFH inherit the defective/mutant genes from both the parents, they have 4–8-fold higher LDL-C concentration (650–1000 mg/dl) as compared to the general population and they develop cutaneous stigmata and atherosclerotic cardiovascular disease during their teens. LDL-C values in HeFH cases are generally between 350–550 mg/dl.
The diagnosis of FH is based on biochemical values of total cholesterol & LDL -C, clinical findings of lipid stigmata, family history of premature CAD/ high LDL-C / cutaneous stigmata, and genetic testing. Early diagnosis is important for the prognosis of the patient and it also has implications for the diagnosis and treatment of family members (cascade testing) who may have inherited the same disorder.
Significance of family history
The family history of premature ischemic heart disease helps to identify an autosomal dominant mode of inheritance. If both parents have very high LDL-C (>190 mg/dL) and/or history of heart disease before age 55-65, this may suggest that they both have FH and can each pass a mutated gene to their children. When each parent has HeFH, by chance, 1 of 4 children will have a normal cholesterol level, 2 of 4 children will have HeFH and 1 of 4 children will have HoFH.
A child or adult with FH requires lifelong medications under medical supervision and lifelong lifestyle intervention. Lipid Association of India (LAI) has taken the initiative to offer free genetic studies and free generic medicines (Statin and Ezetimibe) for the poor patient who are registered with LAI
• Lipid profile estimation of children to be done at 2 years of age in those with family history of FH, premature ASCVD, and adopted children.
• Universal screening of lipids to be carried out at age 20 years or at the time of college admission including estimation of Lp(a) levels.
• Genetic testing should be performed wherever feasible.
• Look for other ASCVD risk factors and manage them appropriately.
• Strict dietary recommendations and lifestyle modifications as advised.
• Drug therapy to be started at age 8 years or earlier in individualized cases.
• Screen Family members for FH (Cascade screening).
• Achieve LDL-C targets as per LAI under medical supervision.
The authors are Senior Interventional Cardiologist and Founder & Chairman, Lipid Association of India, and a Certified Lipidologist by Lipid Association of India respectively