In a 50-year-old man who smokes one pack per day, has a normal BMI of 21, no other medical problems, and an LDL cholesterol of 8.7 mmol/L, which intervention will most effectively reduce his cardiovascular disease risk: gradual reduction of smoking, initiation of a low‑intensity statin, or initiation of a high‑intensity statin?

Start High-Intensity Statin Therapy Immediately

For this 50-year-old smoker with an LDL cholesterol of 8.7 mmol/L (336 mg/dL), high-intensity statin therapy (Option C) is the correct answer and must be initiated immediately to reduce cardiovascular disease risk. Gradual smoking reduction and low-intensity statins are inadequate responses to severe hypercholesterolemia of this magnitude.

Rationale for High-Intensity Statin Therapy

LDL-C ≥190 mg/dL (4.9 mmol/L) is an absolute indication for high-intensity statin therapy without requiring any risk calculation or consideration of other factors. 1, 2 This patient's LDL of 336 mg/dL far exceeds this threshold, placing him at extremely high cardiovascular risk regardless of his smoking status or other risk factors.

• The American College of Cardiology provides a Class I, Level B recommendation that adults ≥21 years with primary LDL-C ≥190 mg/dL should receive high-intensity statin therapy immediately, without waiting for lifestyle modification trials. 1, 2
• High-intensity statin therapy achieves ≥50% LDL-C reduction, which translates to approximately 22% relative risk reduction in cardiovascular events per 1-mmol/L (38.7 mg/dL) LDL-C lowering. 1
• The treatment goal is to achieve at least 50% reduction from baseline LDL-C, with a target of <100 mg/dL (<2.6 mmol/L), and ideally <70 mg/dL for very high-risk patients. 1, 2

Specific Treatment Protocol

Initiate either atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily as first-line high-intensity statin therapy. 1, 2

• These regimens are proven to achieve the required ≥50% LDL-C reduction from baseline. 3, 1
• Atorvastatin 80 mg is often preferred for cost considerations if generic formulations are available. 2
• Measure baseline liver enzymes (ALT/AST) and creatine kinase before initiating therapy. 1, 2
• Reassess LDL-C at 4-12 weeks after initiation to confirm adequate response (≥50% reduction). 1, 2

Why Low-Intensity Statin (Option B) Is Incorrect

Low-intensity statins achieve only <30% LDL-C reduction, which is grossly inadequate for severe hypercholesterolemia of this magnitude. 2

• With an LDL of 336 mg/dL, even a 30% reduction would leave LDL at approximately 235 mg/dL—still dangerously elevated and far above any acceptable target. 3, 2
• Guidelines explicitly recommend high-intensity therapy for LDL ≥190 mg/dL because the cardiovascular risk is so substantial that aggressive treatment is mandatory. 1, 2
• The log-linear relationship between LDL-C and coronary heart disease risk continues at all LDL levels, meaning substantial reduction is required for meaningful risk attenuation. 2, 4

Why Gradual Smoking Reduction (Option A) Is Incorrect

While smoking cessation is critically important, it must be addressed simultaneously with statin initiation—not as an alternative or sequential approach. 1

• Multiple cardiovascular risk factors create cumulative risk requiring concurrent treatment, not stepwise management. 1
• Gradual smoking reduction does not address the immediate and severe cardiovascular threat posed by LDL of 336 mg/dL. 3
• Every tobacco user should be advised to quit completely (not gradually reduce), with counseling, pharmacotherapy including nicotine replacement and bupropion, and referral to cessation programs. 3
• The ACC/AHA guidelines emphasize that smoking cessation and statin therapy are complementary interventions that should both be implemented urgently. 3, 1

Concurrent Smoking Cessation Strategy

Complete smoking cessation (not gradual reduction) must be pursued aggressively alongside statin therapy. 3

• Assess the patient's willingness to quit at every visit. 3
• Develop a concrete plan for quitting that includes behavioral counseling. 3
• Arrange follow-up, referral to specialized cessation programs, and pharmacotherapy with nicotine replacement therapy and/or bupropion. 3
• Urge complete avoidance of environmental tobacco smoke at work and home. 3

Additional Lifestyle Modifications

Therapeutic lifestyle changes should be implemented simultaneously with statin initiation, not as a prerequisite. 1, 2

• Reduce saturated fat to <7% of total calories and limit dietary cholesterol to <200 mg/day. 3, 2
• Increase viscous fiber intake (10-25 g/day) from oats, legumes, and citrus fruits. 2
• Add plant stanols/sterols (2 g/day) for an additional 5-10% LDL-C lowering. 2
• Encourage at least 30-60 minutes of moderate-intensity physical activity daily. 3

Monitoring and Follow-Up

Reassess LDL-C at 4-12 weeks to confirm ≥50% reduction from baseline. 1, 2

• If LDL-C remains >100 mg/dL despite maximally tolerated high-intensity statin, add ezetimibe 10 mg daily for an additional 15-20% LDL-C reduction. 1, 2
• Monitor for statin-associated muscle symptoms (unexplained muscle pain, tenderness, or weakness). 1, 2
• Once stable target levels are achieved, perform annual lipid monitoring. 2
• For very high-risk patients not at goal on statin plus ezetimibe, consider PCSK9 inhibitors for an additional 50-60% LDL-C reduction. 1, 2

Critical Pitfall to Avoid

Never delay statin initiation to "trial lifestyle modifications first" in patients with LDL ≥190 mg/dL. 1, 2

• The cardiovascular risk is too high to justify any delay in pharmacologic intervention. 1, 2
• Lifestyle modifications should be implemented concurrently, not sequentially. 1, 2
• Do not use moderate- or low-intensity statins as initial therapy—this patient requires high-intensity treatment from the outset. 3, 1