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About Isolated Systolic Hypertension (ISH) in Elderly Patients

Question:

Discuss about the Herapeutic Options for Reducing BP in Elderly Patients with ISH.

Elderly people with hypertension have high rate of sodium sensitivity and isolated systolic hypertension (ISH). People above the age of 50 years have more risk of rise in systolic pressure and decrease in diastolic pressure resulting in ISH. In ISH, systolic pressure is greater than140 mm Hg and diastolic pressure is less than 90 mm Hg (1).  The rise in systolic blood pressure creates risk of cardiovascular disease as well as renal disease. ISH is also seen in conditions of high cardiac output such as hyperthyroidism, aortic insufficiency, anemia and arteriovenous fistula. The condition is most prevalent in elderly due to decrease elasticity of the arteries, degradation of arterial elastin and accumulation of arterial calcium (2). Increased arterial stiffness seen due to systolic hypertension is a major health economic burden for aging society as it elevates morbidity and mortality associated with cardiovascular disease. There are many treatment options for ISH in elderly which may involve pharmacological and non-pharmacological treatment options. The purpose of this report is to explore research articles related to therapeutic interventions for treatment of ISH in elderly and determine the advantages and disadvantages of each approach for recovery of elderly patients.

The review of recent literature related to therapeutic treatment options for ISH suggest three possible interventions for reducing blood pressure in older patients. These include cholecalciferol treatment, arteriovenous anastomosis and other pharmacological intervention. One of the research article used placebo-controlled randomized trial method to investigate whether cholecalciferol supplementation is beneficial for reducing BP in older patients with ISH. The Vitamin D in ISH (VitDISH) was conducted to identify impactof high dose cholecalciferol on blood pressure and vascular functions of older patients. Participants with ISH older than 70 years were allocated the intervention or placebo in 1: 1 ratio. The primary outcome measure with the trial medication was observed the next day. The secondary outcome measure included 24- blood pressure, marker of cardiovascular risk and endothelial function. The research finding showed that treatment group and placebo groups had no difference in systolic blood pressure. In treatment group, the systolic blood pressure decreased by 2.7 mm Hg compared to 14.9 mm Hg in placebo group. The study finding is consistent with other findings, which showed that Vitamin D supplementation leads to little reduction in BP level, and this study revealed lack of efficacy of Vitamin D in reducing blood pressure (3).

Another option to interventional therapy for reducing blood pressure in elderly patients with ISH includes renal denervation and development of arteriovenous anastomosis on affected patient using ROX coupler (4). This form of innovative approach to hypertension was selected due to rise in prevalence rate of treatment-resistant hypertension despite presence of safe hypertensive drug classes (5). The purpose of the research article was to analyze the impact of ROX coupler implantation in patients with ISH compared to patient with combined hypertension (CH) as blood pressure response after renal denervation is high in patients with CH. A randomized controlled ROX hypertension study was conducted with treatment resistant hypertension participants. The measurement of baseline office systolic BP and ambulatory systolic BP in participants revealed no difference in values between patients with CH and ISH. Creation of ROX coupler led to reduction in both values (4). Hence, contrary to other research, the response to ROX coupler is same in patients with CH and ISH.

Therapeutic Interventions for ISH in Elderly Patients


Review of other articles related to therapeutic options in treating ISH in elderly revealed the role of antihypertensive drug in stepped doses to eliminate risk and morbidity associated with the disease. As ISH is potential risk factor for cardiovascular disease due to stiffening of artery, the role of drug therapy has been critical in treating the condition. However, as the role of 4 major class of antihypertensive therapy (perindopril, bendrofluazide, atenolol and lercanidipine) is not clear, randomized controlled study was done with untreated systolic hypertension patient to analyze the effect of these drugs on reducing blood pressure and arterial stiffness. Following two weeks of placebo therapy and active therapy with the drugs, it was found that central PP reduced only by perindopril, bendrofluazide, lercanidipine and not atenolol. Hence, similar reduction in peripheral systolic and PP was observed with the four drugs, but central pressure and augmentation index varied. Therefore, choice of therapy should be dependent on these variations.

The review of the articles related to therapeutic options for reducing BP in elderly patients with ISH reveals several strength and weakness of the study. In case for intervention related to cholecalciferol for treating ISH, modest reduction in systolic BP was clearly justified by the researcher (3). The result is consistent with another systematic review and meta-analysis of the effect of Vitamin D supplementation on blood pressure, which revealed that Vitamin D supplementation is ineffective agent for lowering BP and very little response to treatment was found (7). While evaluating the effectiveness of Vitamin D implementation, no adverse event or complication was seen in participants. However, high dose was associated with increase in fall. Some of the strength of this article is that participants with wide range if comorbidity and medication used was chosen which in parallel with issues seen in real world in these patients. The intervention also helped to maintain the 250 HD level (3). Hence, Vitamin D supplementation may reduce the risk of cardiac failure in older people but it cannot prevent stroke in patients (8). The analysis of the research article also revealed certain weakness of the study. Firstly, this study lacked generalizability as patients with only white ethnicity was selected for the study and not other group of patient. Furthermore, frequent doses of Vitamin D are paramount to maintain serum 250 HD level and high dose might have affected the result (9). Besides this, taking small sample size limits the clinical relevance of the study for individual patients.

The advantage of the arteriovenous anastomosis as an intervention for lowering blood pressure is realized due to their potential in addressing problems of recurrence of symptoms despite pharmacological treatment and adherence with medications. The ROX arteriovenous coupler helps in continued reduction of BP by adding a low resistance venous segment to the central arterial tree. Use of this coupler has been found with significant BP reduction in patient with uncontrolled hypertension (9). While analyzing the research article related to the effect of ROX coupler in reducing BP in ISH elderly patients, the reliability of the research is enhanced by proper comparison of BP reduction in patients with out without stiffened arteries after creating a ROX coupler. Therefore, arteriovenous anastomosis can be new therapeutic options for patient with ISH. The limitations in the research article are the use of small sample size for analysis and lack of consideration of direct parameters of arterial stiffness (4).

Cholecalciferol Treatment for Reducing Blood Pressure in Patients with ISH


Hypertensive agent has been considered as an important therapeutic option for patients with ISH. However, due to the revision in the hypertension treatment guidelines, it is necessary to analyze the effect of different classed of antihypertensive drugs on high-risk population (11). With the change in treatment guideline, the article related to comparison of the effects of antihypertensive agent on ISH patients is considered important. The results finding supported the fact that there might be different outcomes for each class of drug and hence patients with increased aortic calcification may require destiffening therapies to promote their recovery (5). The limitations found in the research articles is that reliable data cannot be generated as changes in pulse wave velocity can be seen in patients only after they take the antihypertensive drug for many years. Hence, time constraints in research and lack of confounding variables further reduce the validity of the article (12).

The critical analysis of the three articles explaining possible intervention for ISH patients illustrates the advantages and disadvantages of each intervention in promoting recovery of patients. This section explains the future course of action to strengthen the finding by means of identifying points to further strengthen the treatments options in the future (13). In case of the first article explaining the effect of certain interventions on treatment process, there is no need for further study or randomized controlled trials in ISH patients group as this study clearly justifies the reason for moderate outcomes observed from Vitamin D supplementation. This outcome is also supported from similar outcome in other research articles (3). However, non-blood pressure effects can enhance the efficacy of Vitamin D supplementation and future research can be done on this area to promote cardiovascular health in elderly (14). The contribution of this research is that it discourages high dose of intermittent cholecalciferol in treating older patients with ISH (3).


The efficacy of the arteriovenous anastomosis is understood from the second article as it reduces office and arterial blood pressure in similar ways in both CH and ISH (3). It also biophysical advantage as creation of the anastomosis restores arterial compliance which tends to shift with aging and ISH. However, there are challenges in treating ISH due to lack of appropriate evidence-based guideline. Use of Antihypertensive medication poses risk to patients as it effect is influenced by vascular aging and arterial stiffness. Hence, proper assessment and clinical strategies may help to establish arteriovenous anastomosis as new therapeutic options for treating patients with ISH (15).

The third article examining the effect of antihypertensive agents in ISH suggest all 4 classes of the drugs are effective in reducing blood pressure, however atenolol had a deleterious effect on PP amplification compared to other drugs (5). With this findings from the research articles, the future course of action suggested from this research study is that clinician should consider the effect of different classes of antihypertensive drug on central and brachial pressure to promote positive outcome for patients(16). Hence, the researcher highlights an urgent need to reduce arterial stiffness by analyzing the factors that determine cardiovascular outcome of patients.

Renal Denervation and Arteriovenous Anastomosis for Reducing Blood Pressure in Patients with ISH

Conclusion

The article review summarized the different therapeutical options available for reducing blood pressure in elderly patients with ISH. The analysis of interventions illustrated in three articles depicts weakness and strength of each approach in reducing the morbidity and risk associated with ISH. Out of the three interventions of antihypertensive agent, the arteriovenous anastomosis was considered as most beneficial interventions as it is associated with minimum complication and anomalies in results. Vitamin D supplementation has not been found to gives sustained relief from ISH and anti-hypertensive medications have certain varied effects for different class of drugs. Hence, alternative intervention of the arteriovenous anastomosis can be considered as an appropriate intervention after addressing little limitation in future studies.

References

O’Rourke MF, Adji A. Guidelines on guidelines: focus on isolated systolic hypertension in youth.

Tsimploulis A, Sheriff HM, Lam PH, Dooley DJ, Anker MS, Papademetriou V, Fletcher RD, Faselis C, Fonarow GC, Deedwania P, White M. Systolic–diastolic hypertension versus isolated systolic hypertension and incident heart failure in older adults: Insights from the Cardiovascular Health Study. International Journal of Cardiology. 2017 Mar 1.

Witham MD, Price RJ, Struthers AD, Donnan PT, Messow CM, Ford I, McMurdo ME. Cholecalciferol treatment to reduce blood pressure in older patients with isolated systolic hypertension: the VitDISH randomized controlled trial. JAMA internal medicine. 2013 Oct 14;173(18):1672-9.

Ott C, Lobo MD, Sobotka PA, Mahfoud F, Stanton A, Cockcroft J, Sulke N, Dolan E, van der Giet M, Hoyer J, Furniss SS. Effect of Arteriovenous Anastomosis on Blood Pressure Reduction in Patients With Isolated Systolic Hypertension Compared With Combined Hypertension. Journal of the American Heart Association. 2016 Dec 1;5(12):e004234.Egan BM. Treatment Resistant Hypertension. Ethnicity & disease. 2015;25(4):495.

Mackenzie IS, McEniery CM, Dhakam Z, Brown MJ, Cockcroft JR, Wilkinson IB. Comparison of the effects of antihypertensive agents on central blood pressure and arterial stiffness in isolated systolic hypertension. Hypertension. 2009 Aug 1;54(2):409-13.

Beveridge LA, Struthers AD, Khan F, Jorde R, Scragg R, Macdonald HM, Alvarez JA, Boxer RS, Dalbeni A, Gepner AD, Isbel NM. Effect of vitamin D supplementation on blood pressure: a systematic review and meta-analysis incorporating individual patient data. JAMA internal medicine. 2015 May 1;175(5):745-54.

Ford, J.A., MacLennan, G.S., Avenell, A., Bolland, M., Grey, A., Witham, M. and RECORD Trial Group, 2014. Cardiovascular disease and vitamin D supplementation: trial analysis, systematic review, and meta-analysis.The American journal of clinical nutrition, 100(3), pp.746-755.

Close GL, Leckey J, Patterson M, Bradley W, Owens DJ, Fraser WD, Morton JP. The effects of vitamin D3 supplementation on serum total 25 [OH] D concentration and physical performance: a randomised dose–response study. British journal of sports medicine. 2013 Feb 14:bjsports-2012.

Lobo MD, Sobotka PA, Stanton A, Cockcroft JR, Sulke N, Dolan E, van der Giet M, Hoyer J, Furniss SS, Foran JP, Witkowski A. Central arteriovenous anastomosis for the treatment of patients with uncontrolled hypertension (the ROX CONTROL HTN study): a randomised controlled trial. The Lancet. 2015 May 1;385(9978):1634-41.

Karnes JH, Cooper-DeHoff RM. Antihypertensive medications: benefits of blood pressure lowering and hazards of metabolic effects. Expert review of cardiovascular therapy. 2009 Jun 1;7(6):689-702.

Dunne SS, Dunne CP. What do people really think of generic medicines? A systematic review and critical appraisal of literature on stakeholder perceptions of generic drugs. BMC medicine. 2015 Jul 29;13(1):173.

Stacey D, Légaré F, Col NF, Bennett CL, Barry MJ, Eden KB, Holmes?Rovner M, Llewellyn?Thomas H, Lyddiatt A, Thomson R, Trevena L. Decision aids for people facing health treatment or screening decisions. The Cochrane Library. 2014 Jan 28.

Vimaleswaran KS, Cavadino A, Berry DJ, Jorde R, Dieffenbach AK, Lu C, Alves AC, Heerspink HJ, Tikkanen E, Eriksson J, Wong A. Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study. The lancet Diabetes & endocrinology. 2014 Sep 30;2(9):719-29.

Mahfoud F, Böhm M. Hypertension: Arteriovenous anastomosis [mdash] next panacea for hypertension?. Nature Reviews Cardiology. 2015 Apr 1;12(4):197-8.

Moran AE, Odden MC, Thanataveerat A, Tzong KY, Rasmussen PW, Guzman D, Williams L, Bibbins-Domingo K, Coxson PG, Goldman L. Cost-effectiveness of hypertension therapy according to 2014 guidelines. New England Journal of Medicine.
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