Does this adult patient with total cholesterol 170 mg/dL, LDL‑C 116 mg/dL, HDL‑C 27 mg/dL, triglycerides 152 mg/dL, non‑HDL‑C 143 mg/dL, and cholesterol/HDL ratio 6.3 require pharmacologic therapy?

Immediate Statin Therapy Is Required

This patient requires immediate pharmacologic intervention with moderate-to-high intensity statin therapy due to severely low HDL cholesterol (27 mg/dL) combined with an elevated cholesterol/HDL ratio (6.3), which places them at substantially increased cardiovascular risk regardless of the borderline LDL-C level. 1

Critical Risk Assessment

Severely Low HDL-C Mandates Aggressive Intervention

• HDL-C of 27 mg/dL is profoundly low (normal protective threshold is ≥40 mg/dL for men, ≥50 mg/dL for women), representing an independent major cardiovascular risk factor that warrants immediate treatment. 1
• The cholesterol/HDL ratio of 6.3 is markedly elevated and indicates high cardiovascular risk; ratios >5.0 are associated with significantly increased coronary events. 2, 3
• Non-HDL cholesterol of 143 mg/dL (total cholesterol minus HDL-C) captures all atherogenic lipoproteins and serves as a secondary treatment target; for patients with multiple risk factors, the goal is <130 mg/dL. 1, 4

LDL-C and Triglyceride Context

• LDL-C of 116 mg/dL falls in the "near optimal" range (100-129 mg/dL), but this does not negate the profound risk conferred by the severely low HDL-C. 1
• Triglycerides of 152 mg/dL are mildly elevated (borderline high is 150-199 mg/dL), contributing to the atherogenic lipid profile. 1

Treatment Algorithm

Step 1: Initiate Statin Therapy Immediately

• Start moderate-intensity statin therapy (atorvastatin 10-20 mg daily or rosuvastatin 5-10 mg daily) to achieve LDL-C <100 mg/dL and ≥30% LDL-C reduction. 1, 5
• The primary goal is LDL-C <100 mg/dL, with a secondary goal of non-HDL-C <130 mg/dL (30 mg/dL higher than the LDL-C target). 1, 6
• Do not delay statin initiation for a 12-week lifestyle trial when HDL-C is this profoundly low, as the cardiovascular risk is already substantially elevated. 1, 7

Step 2: Concurrent Intensive Lifestyle Modifications

• Reduce saturated fat to <7% of total calories and limit dietary cholesterol to <200 mg/day. 1, 5
• Add 2 g/day of plant stanols/sterols (expected 6-15% additional LDL-C reduction) and 10-25 g/day of soluble fiber. 7, 5
• Engage in moderate-intensity aerobic exercise ≥30 minutes most days (brisk walking, jogging, cycling); exercise volume of 1500-2200 kcal/week can raise HDL-C by 3-6 mg/dL. 5, 6
• If BMI ≥25 kg/m², target 10% body-weight reduction in the first year; each kilogram lost raises HDL-C by approximately 0.4 mg/dL. 5
• Smoking cessation is mandatory if applicable, as smoking independently lowers HDL-C and raises cardiovascular risk. 5

Step 3: Monitoring and Treatment Escalation

• Obtain fasting lipid panel 4-6 weeks after statin initiation to verify adequate response (target ≥30% LDL-C reduction and LDL-C <100 mg/dL). 1, 5
• If LDL-C remains ≥100 mg/dL or non-HDL-C remains ≥130 mg/dL on maximally tolerated statin, add ezetimibe 10 mg daily for an additional 15-20% LDL-C reduction. 7, 6
• Measure baseline hepatic transaminases (ALT/AST) before starting statin and repeat as clinically indicated; assess for muscle symptoms at each visit. 5, 8
• Once goals are achieved and stable, perform annual fasting lipid assessments. 1, 5

Additional Risk Factor Assessment Required

Determine Complete Cardiovascular Risk Profile

• Calculate 10-year ASCVD risk using the Pooled Cohort Equations (incorporating age, sex, race, blood pressure, smoking status, diabetes status). 5
• Screen for risk-enhancing factors including metabolic syndrome, chronic kidney disease, chronic inflammatory disorders, family history of premature ASCVD (first-degree relative <55 years for males, <65 years for females), persistently elevated LDL-C ≥160 mg/dL, high-sensitivity CRP ≥2.0 mg/L, and lipoprotein(a) ≥50 mg/dL. 5, 9
• If 10-year ASCVD risk is ≥7.5%, consider escalating to high-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily) to achieve ≥50% LDL-C reduction. 1, 5

Rule Out Secondary Causes of Low HDL-C

• Obtain thyroid function tests, liver function tests, and urinalysis to exclude hypothyroidism, liver disease, and nephrotic syndrome as secondary causes of dyslipidemia. 7
• Assess for metabolic syndrome (waist circumference ≥94 cm in men or ≥80 cm in women, elevated triglycerides, low HDL-C, elevated blood pressure, impaired fasting glucose). 5

Critical Pitfalls to Avoid

• Do not withhold statin therapy based solely on the "borderline" LDL-C level; the severely low HDL-C (27 mg/dL) and elevated cholesterol/HDL ratio (6.3) independently mandate treatment. 1, 3
• Do not rely on lifestyle modifications alone when HDL-C is this profoundly low; pharmacologic therapy is required to reduce cardiovascular risk. 1, 7
• Do not use the outdated total cholesterol/HDL ratio as the sole treatment guide; focus on achieving LDL-C <100 mg/dL and non-HDL-C <130 mg/dL as primary and secondary targets. 9, 2
• Do not overlook the elevated non-HDL-C (143 mg/dL), which captures all atherogenic lipoproteins and predicts cardiovascular risk as well as or better than LDL-C alone. 1, 4