Hypertension in the elderly: Some practical considerations

Chaudhry, Kashif; Chavez, Patricia; Gąsowski, Jerzy; Grodzicki, Tomasz; Messerli, Franz H.

doi:10.3949/ccjm.79a.12017

Cited by 32 publications

(33 citation statements)

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“…Safety and tolerability of an antihypertensive drug are particularly important in elderly patients, as they are more likely to have renal and hepatic impairment that may affect the pharmacokinetics of the drug and suffer from orthostatic hypotension. 32 In the elderly population, first-line treatments are diuretics and long-acting calcium channel blockers, followed by ARBs. 29 Several studies have demonstrated that ARBs have greater efficacy and tolerability compared with other antihypertensive regimens in elderly populations; 33,34,35 for example, in the LIFE study, a losartan-based regimen was shown to have greater beneficial effects on BP and PP vs. an atenolol-based regimen in patients aged ≥67 years compared with patients aged <67 years.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Sacubitril/Valsartan (LCZ696) Compared With Olmesartan in Elderly Asian Patients (≥65 Years) With Systolic Hypertension

Supasyndh

Wang

Hafeez

et al. 2017

American Journal of Hypertension

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Hypertension is a very common disease in the elderly (aged ≥65 years). 1 More than 50% of the elderly population has hypertension, 2 especially systolic hypertension, which arises primarily due to age-related changes in the arterial structure of large arteries, contributing to the large artery stiffness. 3 These changes lead to loss of arterial elasticity, 4 resulting in elevated systolic blood pressure (SBP) and widened pulse pressure (PP; difference between SBP and diastolic blood pressure [DBP]). 1 Studies have shown that elevated SBP has a stronger association with adverse cardiovascular (CV) outcomes than elevated DBP in the elderly. 1,5,6 Furthermore, lowering of SBP has been shown to reduce the risk of CV events in elderly patients. 7 A strong association between hypertension and CV events has been reported in Asian population. 8 Olmesartan is one of the most widely prescribed angiotensin II receptor blockers (ARBs) for the treatment of systolic hypertension in elderly patients, 10 including Asians. 11 Despite the available antihypertensive treatments, blood pressure (BP) control is poor in Asian patients. 12 In addition, SBP is considered more difficult to control than DBP, particularly in elderly patients, 13,14 which further suggests the need to develop more effective treatments to target the underlying causes of systolic hypertension in this population.BP is modulated by counter-regulatory neurohormonal interactions between natriuretic peptides, the sympathetic nervous system, and the renin-angiotensin-aldosterone system. 15 Natriuretic peptide levels can be enhanced by inhibiting the enzyme neprilysin, which catalyzes the degradation of multiple vasoactive peptides in the CV system, including natriuretic peptides. 16,17 Blockade of the angiotensin receptor reduces sodium and water retention and inhibits cardiac hypertrophy and remodeling (arterial stiffness). 18,19 Considering the age-related changes to arteries underlying OBJECTIVESystolic hypertension is common in elderly patients and remains a challenge to treat effectively. The efficacy and safety of sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, vs. olmesartan was evaluated in elderly Asian patients (≥65 years) with systolic hypertension. METHODSIn this randomized, double-blind, 14-week study, patients initially received once-daily sacubitril/valsartan 100 mg or olmesartan 10 mg, increased to sacubitril/valsartan 200 mg or olmesartan 20 mg at week 4. At week 10, for patients with blood pressure (BP) >140/90 mm Hg, the doses were up-titrated to sacubitril/valsartan 400 mg or olmesartan 40 mg. The primary assessment was superiority of sacubitril/valsartan vs. olmesartan in reducing office mean sitting (ms) systolic BP (msSBP) from baseline at week 10. Secondary efficacy assessments included changes from baseline in ms diastolic BP (msDBP), ms pulse pressure (msPP), 24-hour mean ambulatory (ma) BP (maBP), and maPP at week 10; msBP and msPP at weeks 4 and 14. RESULTSOverall, 588 patients were randomized (...

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Sacubitril/Valsartan (LCZ696) Compared With Olmesartan in Elderly Asian Patients (≥65 Years) With Systolic Hypertension

Supasyndh

Wang

Hafeez

et al. 2017

American Journal of Hypertension

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“…Sirt3 is a nuclear-encoded protein, however, the majority of Sirt3 translocates to mitochondria (29). Clinical studies have shown that Sirt3 expression declines by 40% by age 65 paralleling the increased incidence of hypertension (28, 30). Angiotensin II and inflammation also mediate the decline in Sirt3 activity (31).…”

Section: Introductionmentioning

confidence: 99%

“…It is interesting that multiple risk factors for hypertension are associated with the reduced Sirt3 expression and activity. For example, Sirt3 activity is metabolically downregulated by increased Acetyl-CoA and reduced NAD + in metabolic syndrome, hyperlipidemia, diabetes and sedentary lifestyle while aging and smoking reduces Sirt3 expression (Figure 3) (30, 36*). It has been suggested that dietary supplementation of Sirt3 activating compounds such as resveratrol can be beneficial (37, 38).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, Sirt3 is one of the potential candidates for age-associated development of cardiovascular diseases. Indeed, Sirt3 expression declines by 40% by age 65 paralleling the increased incidence of hypertension (30). Sirt3 activation of mitochondrial metabolism by deacetylation of key Krebs cycle enzymes, promotes fatty acid β-oxidation, activates complex I, improves antioxidant defense by activation of NADPH producing isocitrate dehydrogenase and increasing SOD2 activity (27, 44).…”

Section: Introductionmentioning

confidence: 99%

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Contribution of mitochondrial oxidative stress to hypertension

Dikalov

Dikalova

2016

Current Opinion in Nephrology and Hypertension

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Purpose of review In 1954 Harman proposed the free radical theory of aging, and in 1972 he suggested that mitochondria are both the source and the victim of toxic free radicals. Interestingly, hypertension is age-associated disease and clinical data show that by age 70, 70% of the population has hypertension and this is accompanied by oxidative stress. Antioxidant therapy however is not currently available and common antioxidants like ascorbate and vitamin E are ineffective in preventing hypertension. The present review focuses on molecular mechanisms of mitochondrial oxidative stress and therapeutic potential of targeting mitochondria in hypertension. Recent findings In the past several years, we have shown that the mitochondria become dysfunctional in hypertension and have defined novel role of mitochondrial superoxide radicals in this disease. We have shown that genetic manipulation of mitochondrial antioxidant enzyme superoxide dismutase (SOD2) affects blood pressure and have developed mitochondria-targeted therapies such as SOD2 mimetics that effectively lower blood pressure. The specific mechanism of mitochondrial oxidative stress in hypertension, however, remains unclear. Recent animal and clinical studies have demonstrated several hormonal, metabolic, inflammatory, and environmental pathways contributing to mitochondrial dysfunction and oxidative stress. Summary Nutritional supplements, calorie restriction, and life style change are the most effective preventive strategies to improve mitochondrial function and reduce mitochondrial oxidative stress. Aging associated mitochondrial dysfunction, however, reduces efficacy of these strategies. Therefore, we propose that new classes of mitochondria-targeted antioxidants can provide high therapeutic potential to improve endothelial function and reduce hypertension.

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“…1 Essential hypertension develops in ≈60% of individuals by the age of 60, but its characteristics in older people differ from those seen in the middle-aged, being associated more often with complications in the older-aged. 2 Hypertension is one of the most common known risk factors for orthostatic hypotension in the elderly persons. 3 Among the less studied risk factors for this orthostatic hypotension, poor vitamin D status is increasingly attracting interest because of recent research showing a strong relationship between serum 25-hydroxyvitamin D (25OHD) and blood pressure.…”

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confidence: 99%

Serum 25-Hydroxyvitamin D and Orthostatic Hypotension in Old People

et al. 2014

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O rthostatic hypotension is a common condition in old people and increases exponentially with age. Among community-dwelling subjects aged >65 years, its prevalence is ≈20%, and in people aged >75 years, it is as high as 30%. 1Orthostatic hypotension is associated with significant cardiovascular morbidities, falls, fractures, and a higher mortality risk. Many factors are related to this condition, including age-associated changes in blood pressure regulation, rapid posture changes, autonomic insufficiency, cardiovascular diseases, or any acute illnesses involving fluid loss.1 Essential hypertension develops in ≈60% of individuals by the age of 60, but its characteristics in older people differ from those seen in the middle-aged, being associated more often with complications in the older-aged.2 Hypertension is one of the most common known risk factors for orthostatic hypotension in the elderly persons. 3Among the less studied risk factors for this orthostatic hypotension, poor vitamin D status is increasingly attracting interest because of recent research showing a strong relationship between serum 25-hydroxyvitamin D (25OHD) and blood pressure. 25OHD levels have been correlated with both the prevalence and the incidence of hypertension, and low 25OHD levels were found to be associated with higher diastolic and systolic blood pressure levels. [4][5][6][7][8][9] Vitamin D receptors are found in endothelial cells, suggesting a possible role for this vitamin in modulating vascular response during orthostatism. 10 McCarroll et al 11 found a significant difference in 25OHD levels between individuals with and without orthostatic hypotension and suggested a possible role for vitamin D status in the pathogenesis of this condition in old people. Research on this association in the elderly persons is lacking, however, and although Abstract-Interest in the association between serum 25-hydroxyvitamin D (25OHD) and blood pressure has increased because recent research showed a close relationship between them, but there is still little information on the possible association between 25OHD and orthostatic hypotension. The aim of this study was to explore the relationship of 25OHD levels with any presence of orthostatic hypotension in a large group of older people. This study was part of the Progetto Veneto Anziani (Pro.V.A.), an Italian population-based cohort study involving people aged >65 years. In this cross-sectional work, we considered 2640 (1081 men and 1559 women) with a mean age of 73.8±6.8 years. Orthostatic hypotension was defined as a drop of ≤20 mm Hg in systolic or ≤10 mm Hg in diastolic blood pressure <3 minutes of orthostatism. Orthostatic hypotension was identified in 32.2% of the sample. The prevalence of orthostatic hypotension was higher in individuals with 25OHD levels <50 nmol/L, but this trend was not significant (P=0.13). Individuals who had orthostatic hypotension had significantly lower 25OHD levels than those who did not (75.0±51.4 versus 82.6±54.0 nmol/L; P<0.0001). On logistic regression analysis, th...

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Hypertension in the elderly: Some practical considerations

Cited by 32 publications

References 54 publications

Efficacy and Safety of Sacubitril/Valsartan (LCZ696) Compared With Olmesartan in Elderly Asian Patients (≥65 Years) With Systolic Hypertension

Efficacy and Safety of Sacubitril/Valsartan (LCZ696) Compared With Olmesartan in Elderly Asian Patients (≥65 Years) With Systolic Hypertension

Contribution of mitochondrial oxidative stress to hypertension

Serum 25-Hydroxyvitamin D and Orthostatic Hypotension in Old People

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