Controversy and uncertainty: Prescribing statins

Question 1

What is atherogenesis?

Answer 1

• Process of atheroma formation in arteries due to endothelial dysfunction

Question 2

How do atheromas form?

Answer 2

Endothelial dysfunction → adhesion molecule expression → monocyte recruitment → LDL oxidation → foam cell formation → connective tissue deposition → atheroma growth

Question 3

What are lipoproteins?

Answer 3

• Complexes of lipids and cholesterol, transporting them in the bloodstream

Question 4

Types of lipoproteins by size and density:

Answer 4

• HDL-C (7-20nm) – returns cholesterol from tissues to plasma
• LDL-C (20-30nm) – main cholesterol source for tissues, but high levels increase atherosclerosis risk
• VLDL (30-80nm) – transports triglycerides from liver
• Chylomicrons (100-1000nm) – largest, transport dietary fat

Question 5

Why is LDL considered high-risk?

Answer 5

• Oxidized LDL (oxLDL) attracts macrophages → foam cell formation → plaque development

Question 6

What is lipoprotein(a) and how does it contribute to disease?

Answer 6

• Special LDL subtype containing apo(a), structurally similar to plasminogen → prevents fibrinolysis → increases thrombosis risk

Question 7

What are NHS guidelines for “safe” cholesterol?

Answer 7

• Total cholesterol:
• ≤ 5 mmol/L (healthy adults)
• ≤ 4 mmol/L (high-risk patients)
• LDL-C:
• ≤ 3 mmol/L (healthy adults)
• ≤ 2 mmol/L (high-risk patients)
• HDL-C: Ideal ≥ 1 mmol/L, lower increases heart disease risk
• Total/HDL ratio: Should be ≤ 4:1

Question 8

What enzyme do statins inhibit?

Answer 8

• HMG-CoA reductase, blocking conversion of HMG-CoA to mevalonic acid (rate-limiting step of cholesterol synthesis)

Question 9

How do statins reduce LDL-C levels?

Answer 9

• Reduced cholesterol synthesis → increased LDL receptor expression on hepatocytes → greater LDL uptake → lower plasma LDL-C levels

Question 10

Why are statins administered at night?

Answer 10

• Cholesterol synthesis peaks in early morning, so nighttime dosing maximizes inhibition

Question 11

• What conditions are statins highly effective for?

Answer 11

• Occlusive vascular disease – reduces risk of heart attacks & strokes

Question 12

• Why are statins prescribed to “at-risk” patients without cardiovascular disease?

Answer 12

• Guidelines now recommend preventative use based on risk factors (age, BMI, blood pressure, QRISK2 scores)

Question 13

How did guideline expansions increase prescriptions?

Answer 13

• 2001 revision increased US statin prescriptions from 13M to 36M, despite most patients (~75%) having no coronary disease

Question 14

• Abramson & Wright study (2007): What did pooled trial data suggest?

Answer 14

• Statins had no mortality benefit in primary prevention
• Reduced cardiovascular events by only 1.5%
• No benefit in females
• High-risk males (30-69 years) had some benefit, but 50 patients needed treatment for 5 years to prevent 1 event

Question 15

Why do health authorities continue statin prescriptions despite controversy?

Answer 15

• Cardiovascular events are major causes of death
• Post-heart attack care is a huge financial burden
• Patient compliance with lifestyle interventions is low
• Statins are well tolerated with generally few side effect

Question 16

• US Preventive Services Task Force (2022): What did they conclude?

Answer 16

• Moderate benefit for adults 40-75 with ≥10% 10-year CVD risk
• Small benefit for 7.5-10% risk patients
• Insufficient evidence for primary prevention in patients 76+ years

Question 17

NICE guideline update (2023): What changed?

Answer 17

• Previously: Atorvastatin prescribed for patients >10% cardiovascular event risk
• Now: Encourages shared decision-making to offer statins below 10% risk threshold

Question 18

What concerns exist about pharmaceutical involvement in statin guidelines?

Answer 18

• Lobbying & PR campaigns expanded prescription eligibility
• Statins are highly profitable drugs
• Industry investment in marketing & medical sales influences healthcare decision

Question 19

• What are the potential benefits of statin awareness?

Answer 19

• Increased public awareness of hyperlipidemia → better lifestyle choices

Question 20

• What are Ozempic & Wegovy?

Answer 20

• GLP-1 receptor agonists, mimic post-meal GLP-1 release

Question 21

What were they originally developed for? (ozemoic and wegovy)

Answer 21

• Type 2 diabetes treatment, now applied to weight loss

Question 22

What impact could GLP-1 agonists have if approved for obesity treatment?

Answer 22

• Major increase in usage → potential public health benefits, but controversy over pharmaceutical-driven expansion