THE DEVELOPMENT OF RESISTANT HYPERTENSION INDEPENDENT OF THE PRECEDING PERIOD OF THE BLOOD PRESSURE CONTROL IS ASSOCIATED WITH THE INCREASED RISK OF CARDIOVASCULAR EVENTS AND DEATH

Abstract Introduction Nocturnal blood pressure (BP) and early morning BP surge have consistently been found to be a better prognostic marker of cardiovascular outcome than daytime BP. Most anti-hypertensive show greater blood pressure-lowering effect in the first 12 hours compared to the next 12 hours. Several prospective studies have shown better BP regulation and improved cardiovascular risk when anti-hypertensive are ingested at bedtime versus at awakening. Purpose In patients with hypertension does evening dosing of anti-hypertensive compared to morning dosing led to better reduction in pressure, blood pressure control and reduced cardiovascular morbidity. Methods A meta-analysis was performed based on randomized controlled trials obtained from Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Medline and Medline ahead of print published between 2000 and 2020. Main outcome measures include mean 24 hour systolic and diastolic blood pressure, cardiovascular events as well as prevalence of blood pressure in control. Data synthesis and analysis was done using RevMan 5.3 using a random effects model. Results A total of 40 randomized controlled trials, representing 44,167 patients were included in this meta-analysis. Most studies evaluate the administration of mixed anti-hypertensive with ≥1 medication ingested at bedtime, calcium channel blockers (CCBs) or angiotensin receptor blockers (ARBs) with sample sizes ranging from 30 to 19,084 patients. Evening administration of anti-hypertensive was found to significantly lower 24-hour systolic blood pressure (Mean difference = −1.05, 95% CI: −2.01 to −0.10, p=0.03) and 24-hour diastolic blood pressure (Mean difference = −1.09, 95% CI: −1.68 to −0.50, p=0.0003). Prevalence of controlled blood pressure was found to significantly increase with evening dosing (RR=1.15, 95% CI: 1.03 to 1.28, p=0.01). Significant reduction in cardiovascular events were found in the evening dosing group (RR=0.48, 95% CI: 0.03 to 0.68, p=<0.00001). Discussion Reduction in night-time blood pressure especially among non-dippers as reported in previous studies and higher prevalence of controlled blood pressure may explain the greater than 50% reduction in cardiovascular events in the evening dosing group. This marked benefit from a simple and inexpensive strategy certainly has great potential to benefit patients in practice. Even so, few studies have reported the prevalence of blood pressure in control (9 studies) and cardiovascular events (6 studies). Few has also studied this in geriatric populations where night-time hypotension and hypoperfusion may bring the most impact. Conclusion For patients with hypertension, evening dosing significantly improves blood pressure control and reduces the risk for cardiovascular events. Careful selection of anti-hypertensive administration time in patients is recommended given the possible benefits. Anti Hypertensive Dosing Forest Plot Funding Acknowledgement Type of funding source: None

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Management of Presumed Acute Kidney Injury during Hypertensive Therapy: Stay Calm and Carry on?

American Journal of Nephrology ◽

10.1159/000505447 ◽

2020 ◽

Vol 51 (2) ◽

pp. 108-115

Author(s):

Teresa K. Chen ◽

Chirag R. Parikh

Keyword(s):

Blood Pressure ◽

Acute Kidney Injury ◽

Serum Creatinine ◽

Blood Pressure Control ◽

Kidney Injury ◽

Pressure Control ◽

Intensive Treatment ◽

Urinary Biomarkers ◽

Increased Risk ◽

Intensive Blood Pressure

Background: Recent studies have demonstrated that intensive blood pressure control is associated with improved cardiovascular outcomes. Acute kidney injury (AKI), however, was more common in the intensive treatment group prompting concern in the nephrology community. Summary: Clinical trials on hypertension control have traditionally defined AKI by changes in serum creatinine. However, serum creatinine has several inherent limitations as a marker of kidney injury, with various factors influencing its production, secretion, and elimination. Urinary biomarkers of kidney injury and repair have the potential to provide insight on the presence and phenotype of kidney injury. In both the Systolic Blood Pressure Intervention Trial and the Action to Control Cardiovascular Risk in Diabetes study, urinary biomarkers have suggested that the increased risk of AKI associated with intensive treatment was due to hemodynamic changes rather than structural kidney injury. As such, clinicians who encounter rises in serum creatinine during intensification of hypertension therapy should “stay calm and carry on.” Alternative explanations for serum creatinine elevation should be considered and addressed if appropriate. When the rise in serum creatinine is limited, particularly if albuminuria is stable or improving, intensive blood pressure control should be continued for its potential long-term benefits. Key Messages: Increases in serum creatinine during intensification of blood pressure control may not necessarily reflect kidney injury. Clinicians should evaluate for other contributing factors before stopping therapy. Urinary biomarkers may address limitations of serum creatinine as a marker of kidney injury.

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