Treatment of elderly patients with isolated systolic hypertension with isosorbide dinitrate in an asymmetric dosing schedule

Starmans-Kool, Mirian; Kleinjans, H. A. J.; Lustermans, F. A. T.; Kragten, Johannes A.; Breed, J. G. S.; Bortel, L.M.A.B. Van

doi:10.1038/sj.jhh.1000664

Cited by 20 publications

(11 citation statements)

References 31 publications

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“…DBP and heart rate values did not differ from those for placebo. The other study 48 confirmed the reduction in office PP with ISDN after 8 weeks of treatment, without a reduction in DBP. In addition, ambulatory PP decreased with ISDN, whereas it did not change during placebo.…”

Section: Changes In Stiffness and Wave Reflections Induced By Nitratessupporting

confidence: 66%

“…Besides the possible tachyphylaxia, the wellknown side effect of headache might be a disadvantage for the common use of nitrates. Although in 1 study in isolated systolic hypertension side effects were not significantly increased with ISDN than with placebo, 47 in the other study, 48 Ͼ20% of patients dropped out because of headache.…”

Section: Changes In Stiffness and Wave Reflections Induced By Nitratesmentioning

confidence: 99%

“…47 Because ISDN was administered orally at a dose of 20 to 40 mg at 8 AM and 8 PM in 1 study 47 and in an eccentric schedule (at 8 AM and 2 PM) in the other, 48 the long nitrate-free period might contribute significantly to the attenuation of the tolerance phenomenon 45 and to the long-term antihypertensive effect. On the other hand, the well-known tachyphylaxia that occurs with nitrates might be more pronounced for the venous than for the arterial effects of nitrates.…”

Section: Changes In Stiffness and Wave Reflections Induced By Nitratesmentioning

confidence: 99%

“…45 Because the resulting baroreflex response is attenuated with age, a pronounced and selective decrease in SBP is frequently observed in old subjects with systolic hypertension. 46 In 2 double-blind randomized placebo-controlled trials, 47,48 the effect of isosorbide dinitrate (ISDN) was studied in elderly subjects with isolated systolic hypertension. In 1 study, 47 ISDN caused a significant decrease in SBP, from the 8th to the 12th week of treatment.…”

Section: Changes In Stiffness and Wave Reflections Induced By Nitratesmentioning

confidence: 99%

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Pulse Pressure, Arterial Stiffness, and Drug Treatment of Hypertension

2001

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Abstract-Epidemiological studies in the past decade have stressed the importance of pulse pressure as an independent risk factor for cardiovascular morbidity and mortality. We briefly review the epidemiological evidence and discuss in more detail the pathophysiological basis for this observation and the therapeutic consequences. We focus on the vascular determinants of increased pulse pressure. Both longitudinal and cross-sectional components of the vascular system contribute to the shape of the arterial pressure wave and, thereby, to pulse pressure. The primary longitudinal component is the architecture of the arterial tree, which determines the major reflection sites for the pressure wave. The cross-sectional architecture of the vascular system consists of a geometric (diameter) and a structural (composition vessel wall) component. Both diameter and composition of the vessel wall vary greatly when going from central to more peripheral arteries. We review the implications for the functional properties of various arterial segments. Finally, we discuss the therapeutic consequences of targeting pulse pressure rather than mean blood pressure with various drug classes. Among the antihypertensive agents, nitrates, NO donors, and drugs that interfere with the renin-angiotensinaldosterone system may offer useful tools to lower pulse pressure, in addition to mean blood pressure. Future developments may include non-antihypertensive agents that target collagen or other components of the arterial wall matrix. However, large-scale clinical trials will have to confirm the therapeutic value of these agents in the treatment of increased pulse pressure and arterial stiffness. Key Words: antihypertensive agents Ⅲ arterial stiffness Ⅲ epidemiology Ⅲ pulse pressure Ⅲ blood pressure H ypertension is a cardiovascular (CV) risk factor, the mechanisms of which are generally attributed to the reduction in the caliber or number of small arteries or arterioles with a resulting increase in total peripheral resistance and mean blood pressure (MBP). MBP, the product of cardiac output and total peripheral resistance, refers to steady phenomena, considering pressure and flow as constant over time. This definition does not take into account that blood pressure and flow fluctuate during the cardiac cycle. In clinical practice, pressure is defined in terms of systolic (SBP) and diastolic (DBP) blood pressure, which refer to a pulsatile phenomenon, with SBP and DBP representing the extremes of the blood pressure oscillation around a mean value, the MBP. In fact, the blood pressure curve may be considered as the summation of a steady component, MBP, and a pulsatile component, the pulse pressure (PP). 1 Besides the pattern of left ventricular ejection, the determinants of PP (and SBP) are the cushioning capacity (compliance) of arteries and the timing and intensity of arterial wave reflections. 1 Compliance of arteries depends on arterial volume and the elastic properties (distensibility) of arterial walls. Compliance and distensibility are quantit...

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Section: Changes In Stiffness and Wave Reflections Induced By Nitratessupporting

confidence: 66%

Section: Changes In Stiffness and Wave Reflections Induced By Nitratesmentioning

confidence: 99%

Section: Changes In Stiffness and Wave Reflections Induced By Nitratesmentioning

confidence: 99%

Section: Changes In Stiffness and Wave Reflections Induced By Nitratesmentioning

confidence: 99%

See 2 more Smart Citations

Pulse Pressure, Arterial Stiffness, and Drug Treatment of Hypertension

2001

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“…171,172 Nitrates do not substantially affect stiffness of the proximal aorta, yet they reduce PP more selectively than other vasoactive drugs by inducing only minimal changes in diastolic or mean pressure. 173,174 This may occur by a more selective effect on venodilation 175,176 and attenuation of peripheral wave reflections during systole. 176,177 Long-term effects have been limited by development of nitrate tolerance, among other potential mechanisms.…”

Section: Can We Intervene? Reducing Vascular Stiffeningmentioning

confidence: 99%

Mechanisms, Pathophysiology, and Therapy of Arterial Stiffness

Zieman

Melenovský

Kass

2005

ATVB

1,590

1,356

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Abstract-Arterial stiffness is a growing epidemic associated with increased risk of cardiovascular events, dementia, and death. Decreased compliance of the central vasculature alters arterial pressure and flow dynamics and impacts cardiac performance and coronary perfusion. This article reviews the structural, cellular, and genetic contributors to arterial stiffness, including the roles of the scaffolding proteins, extracellular matrix, inflammatory molecules, endothelial cell function, and reactive oxidant species. Additional influences of atherosclerosis, glucose regulation, chronic renal disease, salt, and changes in neurohormonal regulation are discussed. A review of the hemodynamic impact of arterial stiffness follows. A number of lifestyle changes and therapies that reduce arterial stiffness are presented, including weight loss, exercise, salt reduction, alcohol consumption, and neuroendocrine-directed therapies, such as those targeting the renin-angiotensin aldosterone system, natriuretic peptides, insulin modulators, as well as novel therapies that target advanced glycation end products. Key Words: arterial stiffness Ⅲ isolated systolic hypertension Ⅲ mechanisms Ⅲ therapeutics Ⅲ pathophysiology I ncreased central arterial stiffening is a hallmark of the aging process and the consequence of many disease states such as diabetes, atherosclerosis, and chronic renal compromise. Accordingly, there is a marked increase in the incidence and prevalence of clinical surrogate markers of vascular stiffness, such as pulse pressure and isolated systolic hypertension, with age and these associated conditions. [1][2][3][4][5][6] Arterial stiffening is also a marker for increased cardiovascular disease risk, including myocardial infarction, heart failure, and total mortality, as well as stroke, dementia, and renal disease. [7][8][9][10][11][12][13][14] This has been recently reviewed by Safar et al. 15 By altering the resting and stress-induced hemodynamics and energy expenditure, vascular stiffness not only contributes to these clinical repercussions and lowers the threshold for their symptoms but also likely contributes to more dyspnea with exertion and orthostatic hypotension in older adults. Although the structural and cellular changes that underlie arterial stiffness may predispose the vasculature to further insult by atherosclerotic disease, the mechanisms explaining this link are still undergoing investigation. Wang and Fitch provide a recent summary of the putative relationship between arterial stiffness and atherosclerosis. 16 Earlier work on arterial properties focused on fluid mechanics and the impact of hemodynamic and reflective wave properties on the development of arterial stiffness and the arterial waveforms. 17,18 The development of methods to measure and assess specific aspects of arterial stiffness, as recently reviewed by Oliver and Webb,19 greatly facilitated understanding of its role in cardiovascular disease. Here, we build on this earlier review to discuss more recent theories on the mechanisms co...

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Is there a preferred antihypertensive therapy for isolated systolic hypertension and reduced arterial compliance?

Franklin

2000

Current Science Inc

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Isolated systolic hypertension (ISH) is the most common type of hypertension and the most difficult type to control with antihypertensive therapy. ISH, by definition, is wide pulse pressure hypertension resulting largely from excessive large artery stiffness and representing an independent risk factor for cardiovascular disease in the older aged population. Two major intervention studies of ISH have shown significant benefit in reducing systolic blood pressure with active drug therapy, including thiazide diuretics and calcium receptor antagonists. The optimal treatment strategy is to maximize reduction in systolic blood pressure and to minimize reduction in diastolic blood pressure, thereby reducing pulse pressure. All classes of antihypertensive drugs reduce pulse pressure by means of lowering peripheral resistance, but certain drugs like nitrates, angiotensin converting enzyme inhibitors, and other drugs affecting the renin-angiotensin system have multiple actions that improve large artery stiffness and early wave reflection and are especially useful in treating ISH in the elderly.

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Treatment of elderly patients with isolated systolic hypertension with isosorbide dinitrate in an asymmetric dosing schedule

Cited by 20 publications

References 31 publications

Pulse Pressure, Arterial Stiffness, and Drug Treatment of Hypertension

Pulse Pressure, Arterial Stiffness, and Drug Treatment of Hypertension

Mechanisms, Pathophysiology, and Therapy of Arterial Stiffness

Is there a preferred antihypertensive therapy for isolated systolic hypertension and reduced arterial compliance?

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