BP Variability, Arterial stiffness and Cilnidipine - A focus review
As long back as 2600 BCE, that the Chinese Yellow emperors classic of Internal Medicine noted that if too much salt is used in blood, the pulse hardens." The relationship between the palpated pulse and the development of heart and brain afflictions was described by ancient Egyptian physicians in the Ebers Papyrus (1550 BCE). Blood pressure is a physiologic parameter characterized by continuous dynamic fluctuations that occur over time spans ranging from seconds to years. The size and patterns characterizing these BP variations define the term BP variability (BPV). The term BPV encompasses a wide range of BP variations, occurring over seconds or minutes (very short-term BPV), a long 24 hours (short-term BPV, usually assessed by ambulatory BP monitoring), and between days (mid-term or day-to-day BPV, assessed with home BP monitoring). Long-term BPV includes seasonal BP variations and changes between clinic visits over months or years.
Fig. 1: Various types of BPV, their determinants, and prognostic relevance for cardiovascular and renal outcomes. Abbreviations: AHT, antihypertensive treatment; BP, blood pressure; BPV, blood- pressure variability; ESRD, end-stage renal disease; eGFR, estimated glomerular filtration rate
Today, we have ample data that supports the evidence that short term BPV represents a strong and independent risk factor for cardiovascular diseases (CVDs) and the development and worsening of end-organ damage, cognitive decline and mortality in patients of hypertension and diabetes. Especially SBP variability has been known to be linked to macro-, such as myocardial infarction, stroke, and peripheral artery disease, and microvascular complications, such as nephropathy and retinopathy.
Antihypertensive treatment may lead to a reduction in BPV by reducing the average BP (BPV being strongly dependent on BP levels) and by improving baroreflex sensitivity, as shown by changes in heart rate variability. A meta-analysis of randomised trials concluded that the use of CCBs and non-loop diuretics reduce the visit-to-visit BP variability as opposed to beta-blockers, ARBs and ACE inhibitors that were associated with an increase of the visit-to-visit variability in SBP.
The ASCOT-BPLA trial also showed opposite effects of beta-blockers and CCBs on within-individual variability in BP independently of their effects on BP. Results of a study by the Japanese Society of Hypertension (2014) suggest that the combination of CCBs and diuretics or CCBs and ARBs could provide a lower 24-h, daytime or night-time BPV compared with other combinations.
Similar results were seen in another study that addition of CCBs decreased the systolic and diastolic 24-h BPV in hypertensive patients treated with ARBs. In another study conducted in France with a cohort of 2780 treated hypertensive patients concluded that that the use of CCBs and, to a lesser extent, diuretics, was associated with a lower short-term BPV compared with the other classes (ARBs, ACEIs and β-blockers).
Cilnidipine > Produces lesser BP variability as compared to other CCBs, beneficial in patients with cerebrovascular disease
A Japanese study with 309 patients with a history of cerebrovascular disease treated with angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, β blocker, or calcium channel blocker, the 24-hour BP variability was measured. Day time BP variability in patients treated with beta-blockers was higher than those treated with CCBs or ARBs. The study concluded that Cilnidipine may be the better choice of BP management in cerebrovascular disease.
Fig. 2: Cilnidipine shows low BP variability (P=0.0467) as compared to other CCBs.
BP Variability and Arterial Stiffness: Role of Cilnidipine
BPV has been related to arterial stiffness and different antihypertensive drug classes have shown contrasting effects on arterial stiffness. Arterial stiffness may reduce baroreceptor sensitivity, which is a major determinant of BP variability. Arterial stiffness increase seen in the elderly, predisposes, in the presence of state of stress, to an excessive pressure response with related large BP fluctuations. Arterial stiffness independently is an important determinant of cardiovascular events and mortality in general population and in patients with hypertension.
In an Indian study of 60 patients (2015) patients were randomly allocated to either Amlodipine or Cilnidipine for duration of eight weeks. Blood Pressure (BP), Heart Rate (HR), carotid-femoral Pulse Wave Velocity (cf PWV), Augmentation Index (AIx) and Aortic augmentation pressure (AoAP) were measured. The study concluded that the antihypertensive efficacies of both the molecules was similar but Cilnidipine was superior to amlodipine in reducing arterial stiffness.
Another study published in the Journal of hypertension, 2007 compared the effects on renal and vascular endothelial functions and arterial stiffness of amlodipine and cilnidipine, in 50 patients with essential hypertension. The study concluded that the decrease of brachial-ankle pulse wave velocity was significantly larger in patients treated with Cilnidipine than Amlodipine, thus Cilnidipine is more effective in improving arterial stiffness.
To summarize, greater very short- to midterm BPV has been associated with increased cardiovascular disease risk, especially stroke. Studies hypothesize that increased arterial stiffness and maladaptive carotid arterial remodeling may underlie this association. Studies have shown Cilnidipine, a fourth-generation CCB, to be beneficial in reducing BPV as well as improving the aortic blood pressure and AoAP as well as markers of arterial stiffness (cf-PWV & AIx), thus making Cilnidipine a useful CCB in the treatment of hypertension with cardiovascular diseases.
The above article has been published by Medical Dialogues under the MD Brand Connect Initiative. For more details on Cilnidipine click HERE
References:
J Stroke Cerebrovasc Dis 2015 Aug;24(8):1848-54.doi: 10.1016/j.jstrokecerebrovasdis.2015.04.023.Epub 2015 May 14.
Hypertension Research volume 37, pages 585–590 (2014)
J Clin Diagn Res. 2015 Nov; 9(11): FC13–FC16.
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Medicine: July 24, 2020 - Volume 99 - Issue 30 - p e21227 doi: 10.1097/MD.0000000000021227
Hypertension 2018 Oct;72(4):1002-1010. doi: 10.1161/HYPERTENSIONAHA.118.11325
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