Gain-of-function mutations in PCSK9 increase LDL cholesterol by accelerating LDL receptor degradation, helping explain inherited cardiovascular risk. Unlike evolutionary adaptations such as sickle-cell heterozygote advantage, these mutations directly enhance protein activity. Understanding this genetic pathway has transformed cholesterol science and led to powerful new treatments for coronary artery disease.

Cardiometabolic risk develops gradually through visceral fat accumulation, insulin resistance and rising blood pressure. A structured escalation model — from supported self-management to specialist review and selective GLP-1 therapy — allows proportionate intervention before overt cardiovascular disease emerges. Early, coordinated action can alter long-term risk trajectories.

For more in this podcast series see https://feeds.transistor.fm/cardiology-topics-for-medics

Semaglutide’s cardiovascular benefits extend beyond weight loss — it powerfully reduces visceral adipose tissue (VAT), the internal fat that drives inflammation, insulin resistance and small dense LDL. At SCVC, our GLP-1 programme targets VAT directly using personalised VAT scans and flexible dosing to improve long-term heart health.

For full article see blog

As we age — particularly if we have inherited genes that predispose us to metabolic disarray that accompanies modern diet and lifestyles, we start to gain weight as visceral fat increases, and muscle mass declines. This double effect worsens blood pressure, cholesterol triglycerides, and blood sugar — contributing to what is known as the metabolic syndrome. Fat cells that have reached their capacity to store extra energy as a healthy reserve start to cause havoc by releasing free fatty acids and in turn worsens insulin resistance, that steepens the decline in health.

However in many cases if we can reduce visceral fat, rebuild muscle, and reach a caloric deficit, we can reverse many of these effects.

See blog

Hypothyroidism is a very common medical condition. Most patients symptoms improve with standard thyroxine treatment, however some do not. There are some genetic variations that leads to poor conversion of T4 to T3 (the active thyroid hormone).  It is not always possible to tell from TSH and T4 chemistry that this issue is present. This podcast covers a review article published in the Lancet in 2023. 

If you have an underactive thyroid and are taking thyroxine but have hypothyroid symptoms despite apparently 'normal' TSH and T4, especially if you struggle to lose weight and have raised blood cholesterol then it is possible that your T4 to T3 conversion is impaired and T3 supplements may make you feel a lot better. 

The relevance of T3 in the management of hypothyroidism

This podcast is a discussion around 
Guidance Document for GPs on Blood Pressure Management: Timeline of Events - where significant events and research in the evolution of blood pressure management guidelines, focusing particularly on heart failure. It aims to aid General Practitioners (GPs) in the UK in understanding the historical context and current standards for managing blood pressure across various patient demographics.