The edition · Cardiology
Familial hypercholesterolaemia is commoner than we teach, and three liver indices sharpen cardiovascular risk
25,431 German children screened at routine appointments, 318,308 adults followed for 14 years on non-invasive liver markers, a validated risk model for RYR2 CPVT, and what night-time light does to the ventricle.
The edition in brief
Screening 25,431 children aged 5 to 15 at routine paediatric appointments in Bavaria, using a fingertip sample for lipids and then genetic testing in those with LDL cholesterol at or above 3.36 mmol/L, identified familial hypercholesterolaemia-causing variants at a raw rate of 1 in 90; adjusted for recruitment bias the estimate was 1 in 163, against the 1 in 250 usually taught, and consistent with gnomAD and UK Biobank. The proportion testing positive rose from 4.7% at 3.36-3.49 mmol/L to 78.6% above 5.17 mmol/L, and sequencing outperformed a focused variant panel. In 318,308 adults free of liver and cardiovascular disease followed a median 14 years, each of the fatty liver index, FIB-4 and the albumin-bilirubin score independently predicted cardiovascular events, with adjusted hazard ratios of 1.46, 1.66 and 1.42 for the top quartile, and 2.53 for those in the top quartile of all three. An externally validated model for RYR2-mediated catecholaminergic polymorphic ventricular tachycardia on beta-blocker monotherapy achieved a C-index of 0.74 for near-fatal or fatal events in derivation but only 0.60 on external validation. And in 11,071 UK Biobank participants with wrist-worn light sensors and later cardiac MRI, night-time light above 3 lux was associated with concentric left ventricular hypertrophy, impaired strain, and higher subsequent risks of heart failure, atrial fibrillation, myocardial infarction and stroke, much of it statistically mediated by shorter sleep.
Three liver indices you can calculate today predict cardiovascular events
Calculate FIB-4 in patients with metabolic risk factors — it predicts cardiovascular events independently, from bloods you have already taken.
A risk model for CPVT that works better in its own cohort than in yours
Elicit and record the pre-diagnosis arrhythmic history carefully in CPVT — but treat the predicted risk as one input, given a validation C-index of 0.60.
Light at night, and a heart that remodels
When you advise on sleep, advise on darkness too — and treat it as a plausible modifiable exposure rather than an established one.
Statins alongside anticoagulation in venous thromboembolism: a signal, not an answer
No change: prescribe lipid-lowering therapy on its own indications, not as thromboprophylaxis.
When you diagnose familial hypercholesterolaemia, you have diagnosed a family
At the visit where you diagnose familial hypercholesterolaemia, name the first-degree relatives in the notes and hand the patient a letter for them.
Screening children finds familial hypercholesterolaemia at 1 in 163
Treat familial hypercholesterolaemia as about 1 in 160, and in a child with raised LDL cholesterol go to gene sequencing rather than a variant panel.
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