How to manage high ferritin levels and hypertension?

Management of High Ferritin Levels and Hypertension

For patients with both high ferritin levels and hypertension, a step-wise approach should be implemented, starting with evaluation of the cause of high ferritin and treating hypertension according to established guidelines, with calcium channel blockers being particularly beneficial in this population.

Evaluation of High Ferritin

Initial Assessment

• Measure transferrin saturation alongside ferritin to assess iron overload
• Significant values indicating potential iron overload 1:
  • Females: transferrin saturation >45% and ferritin >200 μg/L
  • Males: transferrin saturation >50% and ferritin >300 μg/L

Rule Out Other Causes of Elevated Ferritin

• Inflammation/infection
• Metabolic syndrome
• Liver disease
• Malignancy
• Alcohol consumption

Consider Genetic Testing

• Test for hereditary hemochromatosis (HFE gene mutations - C282Y, H63D) if iron overload is confirmed 1
• Management should be guided by phenotypic presentation rather than genotype alone

Management of High Ferritin

For Confirmed Iron Overload

1. Therapeutic phlebotomy is the mainstay of treatment 2, 1:

   • Induction phase: Weekly phlebotomy (400-500 mL, containing 200-250 mg iron)
   • Continue until ferritin reaches 50-100 μg/L
   • Monitor hemoglobin/hematocrit before each phlebotomy
   • Maintenance phase: Individualized frequency based on reaccumulation rate

2. Lifestyle modifications:

   • Limit alcohol intake
   • Reduce red meat consumption
   • Avoid iron supplements and iron-fortified foods
   • Avoid vitamin C supplements with meals (increases iron absorption)
   • Weight loss if overweight/obese

Management of Hypertension

Step 1: Lifestyle Modifications

• Weight loss if overweight/obese
• DASH diet (high in potassium, low in sodium)
• Physical activity (150 minutes/week of moderate-intensity exercise)
• Moderation or elimination of alcohol consumption
• Sodium restriction (<2300 mg/day)

Step 2: Pharmacological Management

Based on the most recent guidelines 2, 3:

1. First-line therapy:

   • Calcium channel blockers (CCBs) - particularly beneficial as they may help lower ferritin levels 4
   • ACE inhibitors or ARBs
   • Thiazide or thiazide-like diuretics

2. Target blood pressure:

   • For most adults: <130/80 mmHg
   • For older adults (≥65 years): SBP 130-139 mmHg

3. For resistant hypertension 2:

   • Add spironolactone to existing treatment
   • If intolerant to spironolactone, consider eplerenone, amiloride, higher dose thiazide/thiazide-like diuretic, or loop diuretic
   • Or add bisoprolol or doxazosin

Special Considerations

For Patients with Chronic Kidney Disease

• Target systolic BP to 120-129 mmHg if eGFR >30 mL/min/1.73 m² 2
• RAS blockers (ACE inhibitors or ARBs) are recommended, especially with albuminuria

For Patients with Heart Failure

• For HFrEF: Use ACE inhibitors/ARBs, beta-blockers, MRAs, and SGLT2 inhibitors 2
• For HFpEF: Consider SGLT2 inhibitors, ARBs, and/or MRAs 2

For Patients with Diabetes

• Target SBP to 130 mmHg and <130 mmHg if tolerated, but not <120 mmHg 2
• For older people with diabetes (≥65 years), target SBP to 130-139 mmHg

Monitoring

1. For iron status:

   • Monitor ferritin and transferrin saturation every 3 months during initial treatment
   • Once stabilized, monitor at least annually

2. For blood pressure:

   • Home BP monitoring
   • Regular office visits to assess BP control and medication adherence
   • Monitor for adverse effects of medications

Important Clinical Pearls

• Research suggests a relationship between elevated ferritin and hypertension risk 5, 6, 7
• CCBs may have the added benefit of lowering serum ferritin levels in hypertensive patients 4
• Avoid treating based on genotype alone - clinical evidence of iron overload should guide treatment decisions 1
• Consider specialist referral (hematology, gastroenterology) if ferritin exceeds 1000 μg/L or cause remains unclear