Which angiotensin-converting enzyme (ACE) inhibitor should be started in a 26‑year‑old man with obesity (BMI 36 kg/m²), prediabetes (HbA1c 5.9 %), hyperlipidemia, and stage 1 hypertension (average blood pressure ~140/90 mm Hg)?

ACE Inhibitor Selection for a Young Adult with Prediabetes and Stage 1 Hypertension

Start with lisinopril 10 mg once daily as your first-line ACE inhibitor in this 26-year-old patient with obesity, prediabetes, and stage 1 hypertension.

Rationale for ACE Inhibitor Selection

Age-Based Guideline Recommendations

• For patients under 55 years of age, ACE inhibitors or ARBs are the preferred first-line antihypertensive agents according to NICE guidelines 1
• The ASH/ISH guidelines similarly recommend ACE inhibitors or ARBs as initial therapy for patients under 60 years of age 1
• This patient at age 26 clearly falls into the younger age category where renin-angiotensin system blockade is most appropriate 1

Metabolic Considerations

• ACE inhibitors are specifically recommended as first-line therapy in patients with prediabetes and diabetes because they provide both macrovascular and microvascular protection beyond blood pressure reduction 1, 2
• With an HbA1c of 5.9%, this patient has prediabetes and faces high risk of progression to type 2 diabetes, making ACE inhibitors particularly appropriate 1
• ACE inhibitors have demonstrated benefits in delaying progression of diabetic nephropathy, which is relevant given this patient's metabolic risk profile 3, 4

Why Lisinopril Specifically

• Lisinopril provides consistently better 24-hour blood pressure control than either captopril or enalapril when given once daily 3
• Lisinopril is well-studied with proven efficacy at dosages of 20-80 mg once daily for all grades of essential hypertension 5
• The once-daily dosing improves medication adherence, which is critical in a young patient who will require lifelong therapy 5, 6
• Lisinopril 10-40 mg daily is specifically recommended for general hypertension management in multiple guidelines 2

Practical Initiation Strategy

Starting Dose and Titration

• Begin with lisinopril 10 mg once daily as the initial dose for this patient with stage 1 hypertension (BP ~140/90 mmHg) 2, 5
• Monitor blood pressure response over 2-4 weeks before adjusting therapy 1
• If blood pressure remains above target after 2-4 weeks, increase to lisinopril 20 mg daily 2, 5
• Target blood pressure should be <130/80 mmHg given the presence of prediabetes and metabolic syndrome 1

Laboratory Monitoring

• Check serum creatinine and potassium 1-2 weeks after initiating therapy to detect any acute changes in renal function or hyperkalemia 2
• Repeat these labs after any dose increase 2
• This monitoring is particularly important given the patient's obesity and metabolic syndrome, which may predispose to renal dysfunction 4

Anticipating Combination Therapy

Realistic Expectations

• Most patients with diabetes or prediabetes require 2-3 antihypertensive agents to achieve target blood pressure <130/80 mmHg 1, 2
• If lisinopril monotherapy does not achieve target BP after titration to 20-40 mg daily, add a thiazide diuretic or calcium channel blocker as second-line therapy 1, 2
• The preferred two-drug combination is an ACE inhibitor with either a dihydropyridine calcium channel blocker or thiazide diuretic 1

When to Escalate

• If blood pressure remains ≥140/90 mmHg after 3 months of lifestyle modification plus lisinopril at adequate doses, add a second agent 1
• Consider fixed-dose combination pills to improve adherence once combination therapy is needed 1

Critical Caveats

Lifestyle Modification is Essential

• Lifestyle interventions must be initiated simultaneously with pharmacotherapy, not sequentially 1
• Target weight loss toward BMI 20-25 kg/m² and waist circumference <94 cm 1
• Sodium restriction potentiates the therapeutic efficacy of ACE inhibitors 4

Contraindications to Monitor

• Avoid ACE inhibitors if systolic BP drops below 80 mmHg or if baseline serum creatinine >3 mg/dL or potassium >5.5 mEq/L 2
• A reversible rise in serum creatinine of up to 30% after ACE inhibitor initiation is acceptable and may predict better long-term renal protection 4

Alternative ACE Inhibitors

• If this patient develops cardiovascular disease or multiple cardiovascular risk factors in the future, consider switching to ramipril 10-20 mg daily, which has superior cardiovascular outcomes data in high-risk patients 2
• Fosinopril may be preferred if significant renal dysfunction develops, as it requires less dosage adjustment 3