What is the relationship between renin elevation and blood pressure (BP) control?

From the Guidelines

Elevated renin levels should be addressed with specific medication strategies, prioritizing angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) as first-line treatments to control blood pressure and reduce morbidity and mortality. For patients with high renin hypertension, ACE inhibitors like lisinopril (10-40 mg daily) or ARBs such as losartan (25-100 mg daily) are recommended, as they directly target the renin-angiotensin-aldosterone system (RAAS) by blocking the effects of angiotensin II, which is produced in response to renin 1.

Key Considerations

• The goal is to target systolic BP to 130 mmHg in patients with diabetes and <130 mmHg if tolerated, but not <120 mmHg, as recommended by the 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases 1.
• Dual therapy with a RAAS blocker and a calcium channel blocker or diuretic is recommended as first-line treatment for BP control 1.
• The combination of an ACEI and an ARB is not recommended due to the increased risk of adverse effects without additional benefits 1.
• Patients should monitor their blood pressure regularly at home and maintain a low-sodium diet (less than 2,300 mg daily) to enhance medication effectiveness.
• Potassium levels should be monitored when using ACE inhibitors or ARBs, as these can cause hyperkalemia.

Additional Therapies

• If BP remains uncontrolled, adding a calcium channel blocker like amlodipine (5-10 mg daily) or a thiazide diuretic such as hydrochlorothiazide (12.5-25 mg daily) is recommended.
• Beta-blockers like metoprolol (25-100 mg twice daily) can also help by reducing renin secretion from the kidneys.
• The underlying cause of renin elevation should also be investigated, as it could be due to renal artery stenosis, volume depletion, or certain medications.

Lifestyle Modifications

• Guidance on lifestyle changes must be provided for patients with diabetes and hypertension, including dietary modifications and increased physical activity 1.
• Patients with diabetes on combined antihypertensive treatments should be encouraged to self-monitor BP 1.

From the Research

Renin Elevation and BP Control

• Renin inhibitors have been shown to lower blood pressure in patients with primary hypertension, with a dose-dependent effect 2.
• The blood pressure lowering effect of renin inhibitors is similar to that of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) 2, 3.
• Renin inhibitors work by blocking the rate-limiting step in the renin-angiotensin-aldosterone system (RAAS), resulting in decreased angiotensin I and II production and decreased urinary aldosterone excretion 4.
• The RAAS plays a crucial role in regulating extracellular fluid volume and blood pressure, and disturbances in this system can lead to hypertension and other cardiovascular diseases 5, 6.

Comparison with ACE Inhibitors

• Renin inhibitors and ACE inhibitors have been compared in several studies, with no significant difference found in terms of all-cause mortality, myocardial infarction, or adverse events 3.
• Renin inhibitors may have a slightly greater effect on lowering systolic and diastolic blood pressure compared to ACE inhibitors, but this effect is of low certainty and may be due to bias 3.
• More independent, large, long-term trials are needed to compare the effectiveness of renin inhibitors and ACE inhibitors in treating hypertension 3.

Mechanism of Action

• The renin-angiotensin system is a powerful feedback system that regulates blood pressure and volume homeostasis, and disturbances in this system can lead to hypertension and other cardiovascular diseases 6.
• Renin inhibitors block the formation of angiotensin I and II, which are potent vasoconstrictors that also stimulate the release of aldosterone, leading to sodium and water retention 2, 4.
• The intrarenal effects of angiotensin II, including efferent arteriolar constriction and direct effects on sodium transport, are quantitatively more important than those mediated by aldosterone in controlling blood pressure and renal excretion 6.