In a 50‑year‑old man who smokes one pack daily, has hypertension, a normal physical examination, a body‑mass index of 21, and an LDL cholesterol of 8.7 mmol/L, which intervention most effectively reduces his cardiovascular disease risk?

Complete Smoking Cessation and High-Intensity Statin Therapy Are Both Mandatory

This patient requires immediate initiation of high-intensity statin therapy (atorvastatin 40–80 mg or rosuvastatin 20–40 mg daily) combined with complete smoking cessation—not gradual reduction—using pharmacologic aids (nicotine replacement, bupropion, or varenicline) plus behavioral counseling. 1, 2

Why Waiting or Gradual Reduction Are Unacceptable

• LDL-C of 8.7 mmol/L (≈336 mg/dL) exceeds the treatment threshold by approximately 66% and mandates immediate pharmacologic intervention regardless of 10-year risk calculation. 2
• The ACC/AHA provides a Class I recommendation that adults with primary LDL-C ≥4.9 mmol/L (190 mg/dL) must receive high-intensity statin therapy without delay for lifestyle trials. 2, 3
• Waiting until cardiac symptoms manifest is dangerous: this patient already has established hypertension plus severe hypercholesterolemia plus 20 pack-years of smoking—a combination that multiplies cardiovascular risk up to ten-fold compared with isolated cholesterol elevation. 2

Smoking Cessation: Complete, Not Gradual

• Gradual smoking reduction has not been shown to increase the probability of future cessation and does not reduce cardiovascular risk. 1
• European guidelines emphasize that smoking cessation must be complete; there is a dose–response relationship with no lower limit for deleterious effects. 1
• Stopping smoking after a cardiovascular event reduces myocardial infarction risk by 43% (RR 0.57) and the composite endpoint of death/MI by 26% (RR 0.74) compared with continued smoking, with significant morbidity reductions occurring within the first 6 months. 1
• Hypertensive smokers who quit one pack per day can reduce cardiovascular risk by 35–40% quickly. 4

Evidence-Based Smoking Cessation Strategy

• Professional support increases the odds of stopping (RR 1.66,95% CI 1.42–1.94); brief advice plus pharmacologic aids plus follow-up support constitute the most effective intervention. 1
• All forms of nicotine replacement therapy (NRT) increase the rate of quitting by 50–70% (RR for abstinence 1.60 vs. control). 1
• Bupropion aids long-term smoking cessation with similar efficacy to NRT and is specifically mentioned as an evidence-based drug intervention. 1
• Varenicline is also effective; the most effective strategy combines brief interventions, drug therapy, and follow-up support. 1

High-Intensity Statin Therapy

• High-intensity statins (atorvastatin 40–80 mg or rosuvastatin 20–40 mg daily) achieve ≥50% LDL-C reduction, which would lower this patient's LDL-C from 8.7 mmol/L to approximately 4.3 mmol/L (≈166 mg/dL). 2, 3
• The treatment goal is LDL-C <2.6 mmol/L (100 mg/dL), with a more aggressive target of <1.8 mmol/L (70 mg/dL) reasonable given multiple risk factors. 2, 3
• "Low-intensity cholesterol-lowering agents" are inadequate: a low-intensity statin produces <30% LDL-C reduction, which would leave this patient's LDL-C at ≈6.1 mmol/L (235 mg/dL)—well above any acceptable target. 2

Why Both Interventions Must Be Simultaneous

• Cigarette smoking is the most cost-effective target for CVD prevention, and stopping smoking is potentially the most effective of all preventive measures. 1
• Smoking increases cardiovascular risk at any level of blood pressure and greatly amplifies the risk conferred by hypertension and hypercholesterolemia. 4, 5
• The ACC/AHA guidelines emphasize that smoking cessation and statin therapy are complementary interventions that should both be implemented urgently. 2
• Lifestyle measures (including smoking cessation) should be instituted simultaneously with pharmacologic treatment, not sequentially. 1

Hypertension Management

• This patient's hypertension requires optimization to a target BP <140/90 mmHg (or <130/80 mmHg given multiple cardiovascular risk factors). 1
• Thiazide diuretics, ACE inhibitors, or ARBs are preferred first-line agents because they do not adversely affect lipid profiles. 2
• Beta-blockers should be avoided as first-line therapy in patients with metabolic risk factors and dyslipidemia. 2

Monitoring and Follow-Up

• Reassess LDL-C at 4–6 weeks after statin initiation to confirm ≥50% reduction from baseline. 2, 3
• If LDL-C remains >2.6 mmol/L (100 mg/dL) on maximally tolerated high-intensity statin, add ezetimibe 10 mg daily for an additional 15–20% LDL-C reduction. 2, 3
• Verify smoking status at every visit and provide ongoing cessation support with follow-up arrangements. 1
• Monitor for statin-related muscle symptoms (unexplained pain, tenderness, or weakness) and obtain baseline ALT before starting therapy. 2, 3

Critical Pitfalls to Avoid

• Do not postpone statin initiation for a trial of lifestyle modification when LDL-C exceeds 4.1 mmol/L (160 mg/dL) in the presence of multiple risk factors. 2
• Do not prescribe a moderate- or low-intensity statin when high-intensity therapy is indicated by the degree of LDL-C elevation and overall risk burden. 2
• Do not advise gradual smoking reduction; the evidence supports only complete cessation with pharmacologic aids. 1
• Do not wait for cardiac symptoms to manifest before treating severe hypercholesterolemia and smoking in a hypertensive patient. 2