What is the best treatment approach for a 67-year-old female with hypertriglyceridemia (elevated triglycerides) and hypercholesterolemia (elevated cholesterol) who has shown little improvement on lisinopril (angiotensin-converting enzyme inhibitor) 10mg?

Treatment Approach for Hypertriglyceridemia and Hypercholesterolemia with Inadequate Blood Pressure Control

This 67-year-old woman requires immediate initiation of high-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) to address her severely elevated triglycerides (418 mg/dL) and cholesterol (248 mg/dL), while simultaneously optimizing her blood pressure control by increasing lisinopril or adding a second antihypertensive agent. 1

Immediate Lipid Management Priority

Statin Therapy as Foundation

• Initiate high-intensity statin therapy immediately as the cornerstone of treatment, targeting at least a 50% reduction in LDL-C, given her age >40 years and multiple cardiovascular risk factors 1
• High-intensity statins (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) will address both the elevated cholesterol and provide significant triglyceride reduction of 22-45% when baseline triglycerides exceed 250 mg/dL 2
• All statins are effective at reducing triglycerides in hypertriglyceridemic patients, with the effect proportional to their LDL-C lowering potency 2

Addressing Severe Hypertriglyceridemia

• With triglycerides at 418 mg/dL, she is at risk for pancreatitis and requires aggressive triglyceride management 3
• After initiating statin therapy, if triglycerides remain >200 mg/dL after 4-8 weeks, add fenofibrate 54-160 mg daily (starting at 54 mg given her age and need to assess renal function) 3
• Fenofibrate is FDA-approved for severe hypertriglyceridemia and mixed dyslipidemia, though it should be added only after maximizing statin therapy 3

Treatment Goals

• **Primary goal: LDL-C <100 mg/dL** (likely requiring >50% reduction from baseline) 1
• Secondary goal: Triglycerides <150 mg/dL 1
• Tertiary goal: Non-HDL-C <130 mg/dL 1

Blood Pressure Optimization

Inadequate Response to Lisinopril

• After 4 weeks on lisinopril 10 mg with minimal improvement, increase lisinopril to 20-40 mg daily as the first step 4
• Lisinopril is safe and effective when combined with statins, with no negative drug interactions 4
• If blood pressure remains uncontrolled after dose optimization, add a calcium channel blocker (amlodipine 5-10 mg) or thiazide diuretic as second-line therapy 1

Critical caveat: Thiazide diuretics can worsen hypertriglyceridemia and should be avoided or used cautiously in this patient with already severe triglyceride elevation 3, 5

Mandatory Lifestyle Modifications

Dietary Interventions (Must Implement Before and During Drug Therapy)

• Reduce saturated fat to <7% of total calories and cholesterol to <200 mg/day 1, 6
• Eliminate or severely restrict simple sugars and alcohol, both of which significantly elevate triglycerides 1, 3
• Increase soluble fiber intake to 10-25 g/day and consider plant stanols/sterols up to 2 g/day 1, 6
• Adopt a Mediterranean-style diet emphasizing fish, vegetables, legumes, nuts, and whole grains 1

Weight and Physical Activity

• Target BMI 18.5-24.9 kg/m² and waist circumference <35 inches through caloric restriction 1, 6
• Minimum 30 minutes of moderate-intensity physical activity on most days, with progression to 40 minutes of vigorous activity 3-5 days/week if tolerated 1
• Physical activity is particularly important for triglyceride reduction 3

Monitoring and Follow-Up Algorithm

Initial Phase (First 4-8 Weeks)

• Recheck lipid panel at 4 weeks after statin initiation to assess response 3
• Monitor liver enzymes (AST/ALT) and creatine kinase at baseline and 4-8 weeks after statin initiation 3
• Check renal function (creatinine, eGFR) before considering fenofibrate, as dose adjustment is required for renal impairment 3
• Reassess blood pressure weekly until controlled to <140/90 mmHg (or <130/80 mmHg if diabetes present) 1

Secondary Phase (8-12 Weeks)

• If triglycerides remain >200 mg/dL despite maximally tolerated statin therapy, add fenofibrate starting at 54 mg daily 3
• If LDL-C reduction is <50% or LDL-C remains >100 mg/dL, add ezetimibe 10 mg daily to statin therapy 1
• Continue lifestyle modification counseling and assess adherence 6

Long-Term Management

• Lipid panel every 3-6 months until goals achieved, then annually 1
• Consider referral to lipid specialist if goals not achieved after 2 months of maximum-dose combination therapy 1, 3

Critical Pitfalls to Avoid

• Do not delay statin therapy while attempting lifestyle modifications alone—this patient's lipid levels are too severe 1
• Do not use beta-blockers as additional antihypertensive therapy, as they can worsen triglycerides 3, 5
• Do not combine fenofibrate with gemfibrozil due to increased myopathy risk; fenofibrate is the preferred fibrate with statins 3
• Do not ignore secondary causes of dyslipidemia: check TSH, fasting glucose/HbA1c, liver function, and urinalysis 1
• Fenofibrate must be given with meals to optimize bioavailability 3