Genetics

Lipoprotein(a), Familial Hypercholesterolemia and CVD

Lipoprotein(a), Familial Hypercholesterolemia and CVD

Familial hypercholesterolemia (FH) has a high prevalence of cardiovascular morbidity and mortality, due to the lifelong cumulative exposure of high serum cholesterol levels.

The study finds that only a minority of patients are capable of achieving LDLc targets set by the European guidelines. About 25% of FH patients reach LDLc ≤100 mg/dL and only 8% of very high-risk CVD patients reach LDLc ≤70 mg/dL.

Importantly, those with high Lp(a) experienced twice as much CHD events than those with low Lp(a) levels. Specific drug development toward Lp(a) would be a breakthrough in helping patients with familial hypercholesterolemia.

A group of 714 FH adults were followed for about 11 years.

GT

Familial Hypercholesterolemia and CVD risk factors

Familial Hypercholesterolemia and CVD risk factors

Genetic inability to clear LDL-particles leads to familial hypercholesterolemia. Persistent high serum LDLc and total-cholesterol are major cumulative risk factors for premature cardiovascular disease.

The article identifies other independent risk factors contributing to CVD in these patients. Such factors are male sex, smoking, hypertension, diabetes, elevated Lp(a), and family history of CVD.

Obviously, the modifiable contributors; hypertension, smoking and diabetes need to be managed aggressively.

GT

Prolactinoma, pheochromocytoma and MAX gene

Prolactinoma, pheochromocytoma and MAX gene

Pheochromocytomas are rare neuroendocrine tumors. They could be adrenal vs. extra-adrenal, sporadic vs. familial, isolated vs. multifocal, or benign vs. malignant. MAX gene mutation has recently been recognized as an unusual cause of familial pheochromocytoma.

This article documents the first patient with simultaneous germline MAX mutation, pituitary prolactinoma, bilateral pheochromocytoma and mild primary hyperparathyroidism.

Could the germline MAX mutation be a direct cause of prolactinoma as well?

GT

Lipoprotein (a): sneaky and dangerous

Lipoprotein (a): sneaky and dangerous

Lipoprotein (a) is an independent risk factor for poor cardiovascular outcomes. Authors find that PCSK9-i lowers Lp(a) and LDL by 20% and 50% respectively. Lp(a) and LDL reduction are 60% concordant, suggesting that some Lipoprotein (a) improvement could be via non-LDL-receptor pathway. More research is needed as pharmacological options targeting Lp (a) are limited.

GT

Children, Lipodystrophy and Leptin

Children, Lipodystrophy and Leptin

Lipodystrophy (LD) could be familial or acquired, partial or generalized. This original NIH study shows that metreleptin, a leptin analog, can nicely improve LD metabolic anomalies; such as high glucose, triglycerides and liver enzymes. These benefits are expected to decrease long-term lipodystrophy complications in young individuals.

GT

Heterozygous familial hypercholesterolemia & PCSK9 inhibition

Heterozygous familial hypercholesterolemia & PCSK9 inhibition

PCSK9 inhibitors are a new cholesterol-reducing class of medications. In this study, PCSK9 inhibition by alirocumab reduced LDL nicely by about 50% even in individuals with heterozygous familial hypercholesterolemia. Adverse event profile was overall similar between the alirocumab and placebo arm. A group of 1300 patients were followed for about 2 years.

GT

Homozygous Familial Hypercholesterolemia: PCSK9 inhibitor

Homozygous Familial Hypercholesterolemia: PCSK9 inhibitor

This original research shows that PCSK9 inhibitor can lower LDL and Lipoprotein(a) approximately by 25% and 10% in young individuals with severe form of familial hypercholesterolemia, regardless if treated with aphaeresis. 

Although clinical outcomes were not assessed, drop in LDL and L(a) are expected to be beneficial. Study duration was about 2 years. Main adverse events were nasopharyngitis, influenza, headaches and upper respiratory tract infections.

GT

Homozygous familial hypercholesterolemia: LDL Apheresis

Homozygous familial hypercholesterolemia: LDL Apheresis

Homozygous familial hypercholesterolemia results from full deficiency of malfunction of LDL receptors in the liver. Risk of coronary artery disease is skyrocketed. It is often hard to treat with statin-based combination therapy. Lipoprotein apheresis could be the only hope for affected individuals.

Please find below a nice case study of LDL-apheresis effectiveness in 3 siblings. Twice weekly session with 1.5 exchange volume brought LDL-C to target without any noticeable adverse events.

GT