What are the next management steps for a 50‑year‑old woman with uncontrolled hypertension (BP 160/90) after stopping losartan 100 mg daily and amlodipine 10 mg daily, low serum creatinine, mildly elevated AST, LDL‑C 3.70 mmol/L, triglycerides 2.15 mmol/L, mild asthma treated with budesonide/formoterol and methylprednisone, surgical menopause and lumbar scoliosis?

Management of Uncontrolled Hypertension with Dyslipidemia and Mildly Elevated AST

Restart losartan 100 mg and amlodipine 10 mg immediately, add a thiazide-like diuretic (chlorthalidone 12.5–25 mg daily preferred over hydrochlorothiazide 25 mg daily), initiate statin therapy for elevated LDL-C, and investigate the mildly elevated AST before attributing it to medication. 1

Immediate Blood Pressure Management

Restart and Intensify Antihypertensive Therapy

• The patient has stage 2 hypertension (160/90 mmHg) that requires immediate triple therapy rather than restarting only the two previously discontinued medications. 1

• Restart losartan 100 mg daily and amlodipine 10 mg daily immediately, as these were providing some control before discontinuation and the patient has already tolerated them. 1

• Add chlorthalidone 12.5–25 mg once daily in the morning as the third agent to achieve guideline-recommended triple therapy (RAS blocker + calcium channel blocker + thiazide diuretic). 1, 2

• Chlorthalidone is strongly preferred over hydrochlorothiazide because it provides superior 24-hour blood pressure control and has stronger cardiovascular outcome data from the ALLHAT trial. 2

• The 2024 ESC guidelines explicitly state that when BP is not controlled with a two-drug combination, increasing to a three-drug combination is recommended, usually a RAS blocker with a dihydropyridine CCB and a thiazide/thiazide-like diuretic, preferably in a single-pill combination. 1

Blood Pressure Targets and Monitoring

• Target systolic BP of 120–129 mmHg if well tolerated, with a minimum acceptable goal of <140/90 mmHg. 1

• Recheck blood pressure within 2–4 weeks after restarting medications and adding the diuretic, with the goal of achieving target BP within 3 months. 1, 2

• Check serum potassium and creatinine 2–4 weeks after initiating chlorthalidone to detect hypokalemia or changes in renal function, especially given the concurrent use of losartan. 2

Lipid Management

Initiate Statin Therapy

• Start a moderate- to high-intensity statin immediately for LDL-C 3.70 mmol/L (143 mg/dL), non-HDL 4.86 mmol/L (188 mg/dL), and triglycerides 2.15 mmol/L (190 mg/dL). 1

• The patient has multiple cardiovascular risk factors: hypertension, dyslipidemia, surgical menopause (loss of cardioprotective estrogen at age 48), and chronic corticosteroid use for asthma. 1

• Atorvastatin 40–80 mg daily or rosuvastatin 20–40 mg daily would be appropriate high-intensity options to reduce LDL-C by ≥50%. 1

• Amlodipine has been shown to provide an additional LDL-lowering effect beyond its antihypertensive properties, which may provide modest additional benefit. 3

Lipid Monitoring

• Recheck fasting lipid panel 4–12 weeks after statin initiation to assess response and adjust dose if needed. 1

• Target LDL-C <2.58 mmol/L (<100 mg/dL) minimum, ideally <1.8 mmol/L (<70 mg/dL) given her multiple cardiovascular risk factors. 1

Investigation of Mildly Elevated AST

Differential Diagnosis

• AST 46 U/L (normal 5–34) is only mildly elevated and has multiple potential causes that must be investigated before attributing it to medication. 1

• Chronic corticosteroid use (methylprednisolone 16 mg daily) can cause hepatic steatosis and mild transaminase elevation, which is a more likely culprit than losartan or amlodipine. 1

• Other considerations include: non-alcoholic fatty liver disease (especially if overweight), alcohol use, viral hepatitis, autoimmune hepatitis, or hemolysis. 1

Diagnostic Workup

• Check ALT, alkaline phosphatase, total bilirubin, and GGT to characterize the pattern of liver enzyme elevation. 1

• Check hepatitis B surface antigen, hepatitis C antibody, and consider autoimmune markers (ANA, anti-smooth muscle antibody) if other causes are excluded. 1

• Obtain right upper quadrant ultrasound to assess for hepatic steatosis, which is common with chronic corticosteroid use. 1

• Do not discontinue losartan or amlodipine based solely on this mild AST elevation, as both drugs are generally well-tolerated hepatically and the elevation is more likely related to corticosteroid use or other factors. 1

Addressing the Low Creatinine

Clinical Significance

• Creatinine 45.7 μmol/L (0.52 mg/dL) is below the normal range (50.4–98.1 μmol/L) but is not clinically concerning in a 50-year-old woman. 1

• Low creatinine typically reflects low muscle mass rather than renal pathology and does not contraindicate any of the recommended antihypertensive medications. 1

• Calculate estimated GFR using the CKD-EPI equation to assess true renal function, as creatinine alone can be misleading in patients with low muscle mass. 1

Asthma Management Considerations

Antihypertensive Selection in Asthma

• Calcium channel blockers (amlodipine) are safe and preferred in patients with asthma or COPD, as they do not cause bronchoconstriction. 4

• ARBs (losartan) are also safe in asthma and do not affect bronchial reactivity. 1

• Thiazide diuretics (chlorthalidone) are safe in asthma and have no bronchoconstrictive effects. 1

• Beta-blockers are contraindicated in asthma unless there is a compelling indication such as recent myocardial infarction or heart failure, which this patient does not have. 1, 4

Corticosteroid Burden

• Methylprednisolone 16 mg daily is a significant chronic corticosteroid dose that contributes to hypertension, dyslipidemia, hepatic steatosis, and metabolic complications. 1

• Work with the patient's pulmonologist to optimize asthma control and minimize systemic corticosteroid exposure, potentially by maximizing inhaled corticosteroid/LABA therapy (budesonide/formoterol) and considering add-on agents like leukotriene modifiers or biologics. 1

Lifestyle Modifications (Adjunct to Pharmacotherapy)

Dietary Interventions

• Sodium restriction to <2 g/day (≈5 g salt/day) provides a 5–10 mmHg systolic reduction and enhances the efficacy of all antihypertensive classes, especially diuretics and ARBs. 1, 4

• Adopt the DASH dietary pattern (high in fruits, vegetables, whole grains, low-fat dairy; low in saturated fat), which reduces BP by approximately 11.4/5.5 mmHg. 4

Physical Activity and Weight Management

• Regular aerobic exercise (≥30 minutes most days, ≈150 minutes/week moderate intensity) reduces BP by ≈4/3 mmHg and improves lipid profiles. 4

• Weight loss if overweight or obese—losing ≈10 kg reduces BP by about 6.0/4.6 mmHg and improves insulin sensitivity. 4

Alcohol and Tobacco

• Limit alcohol intake to ≤1 drink/day for women (≤100 g/week), as excess consumption interferes with BP control. 1, 4

• Tobacco cessation is mandatory, as tobacco use strongly and independently causes cardiovascular disease and all-cause mortality. 1

Common Pitfalls to Avoid

Medication Errors

• Do not delay restarting antihypertensive therapy—the patient has stage 2 hypertension (160/90 mmHg) requiring immediate action to reduce cardiovascular risk. 1

• Do not restart only the two previous medications without adding a third agent—the patient needs triple therapy to achieve BP control. 1, 2

• Do not combine losartan with an ACE inhibitor (dual RAS blockade), as this increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit. 1

• Do not add a beta-blocker as the third antihypertensive agent in this patient with asthma unless there is a compelling indication (angina, post-MI, heart failure), as beta-blockers are contraindicated in asthma and less effective than diuretics for stroke prevention. 1, 4

Diagnostic Errors

• Do not attribute the mildly elevated AST to losartan or amlodipine without investigation—chronic corticosteroid use is a more likely cause. 1

• Do not assume treatment failure without first confirming medication adherence once therapy is restarted. 1, 2

• Do not overlook the contribution of chronic corticosteroid therapy to hypertension, dyslipidemia, and hepatic steatosis. 1

Follow-Up Plan

Short-Term (2–4 Weeks)

• Recheck blood pressure, serum potassium, and creatinine after restarting triple therapy. 1, 2

• Obtain liver function panel (ALT, AST, alkaline phosphatase, total bilirubin, GGT) and right upper quadrant ultrasound to investigate AST elevation. 1

Medium-Term (4–12 Weeks)

• Recheck fasting lipid panel to assess statin response and adjust dose if needed. 1

• Reassess blood pressure control—if BP remains ≥140/90 mmHg despite optimized triple therapy, add spironolactone 25–50 mg daily as the preferred fourth-line agent for resistant hypertension. 1, 2

Long-Term (3–6 Months)

• Achieve target BP <130/80 mmHg and LDL-C <1.8 mmol/L (<70 mg/dL) within 3 months of therapy modification. 1

• Work with pulmonology to minimize systemic corticosteroid exposure and optimize asthma control with inhaled therapies and add-on agents. 1

• Monitor for hypertension-mediated organ damage (renal function, proteinuria, left ventricular hypertrophy) and ensure regression with adequate BP control. 1