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

Franklin, Stanley S.

doi:10.1007/s11906-000-0008-0

Cited by 33 publications

(23 citation statements)

References 71 publications

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“…13,29 An alternative or supplemental strategy that holds some promise is the development of more potent antihypertensive agents that have minimal side effects and are specifically targeted to reduce SBP. 30 …”

Section: Discussionmentioning

confidence: 99%

Predominance of Isolated Systolic Hypertension Among Middle-Aged and Elderly US Hypertensives

et al. 2001

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Abstract-The purpose of the present study was to examine patterns of systolic and diastolic hypertension by age in the nationally representative National Health and Nutrition Examination Survey (NHANES) III and to determine when treatment and control efforts should be recommended. Percentage distribution of 3 blood pressure subtypes (isolated systolic hypertension, combined systolic/diastolic hypertension, and isolated diastolic hypertension) was categorized for uncontrolled hypertension (untreated and inadequately treated) in 2 age groups (ages Ͻ50 and Ն50 years). Overall, isolated systolic hypertension was the most frequent subtype of uncontrolled hypertension (65%). Most subjects with hypertension (74%) were Ն50 years of age, and of this untreated older group, nearly all (94%) were accurately staged by systolic blood pressure alone, in contrast to subjects in the untreated younger group, who were best staged by diastolic blood pressure. Furthermore, most subjects (80%) in the older untreated and the inadequately treated groups had isolated systolic hypertension and required a greater reduction in systolic blood pressure than in the younger groups (-13.3 and -16.5 mm Hg versus -6.8 and -6.1 mm Hg, respectively; Pϭ0.0001) to attain a systolic blood pressure treatment goal of Ͻ140 mm Hg. Contrary to previous perceptions, isolated systolic hypertension was the majority subtype of uncontrolled hypertension in subjects of ages 50 to 59 years, comprised 87% frequency for subjects in the sixth decade of life, and required greater reduction in systolic blood pressure in these subjects to reach treatment goal compared with subjects in the younger group. [1][2][3][4][5] and that treating isolated systolic hypertension (ISH) in the elderly reduces risk of cardiovascular disease events. 6,7 Despite the strength of these observational and intervention studies, only about one quarter of hypertensive individuals are being treated to goal. 8 Recently, the Coordinating Committee of the National High Blood Pressure Education Program (NHBPEP), recognizing the magnitude of this public health problem, stated that SBP in general and ISH in particular should become the major criteria for the diagnosis, staging, and therapeutic management of hypertension in the middle-aged and elderly. 9 ISH is strongly age dependent. Both the Framingham Heart Study and the nationally representative National Health and Nutrition Examination Survey (NHANES) III (conducted in 1988 to 1994) showed that a similar pattern of progressively increasing SBP occurs throughout adult life in untreated individuals. 10,11 In contrast, DBP was shown to increase in adults until age 50 years and decline from the sixth decade forward. 10,11 This age-related pattern of increasing rates of ISH for ages Ն50 years was not only observed in the Framingham Heart Study 10 and in NHANES III participants, 11 but also in a meta-analysis of 10 studies that reported the prevalence of ISH. 12 In total, these studies suggest that age 50 years is a useful cutpoint to dichotomize a...

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Section: Discussionmentioning

confidence: 99%

Predominance of Isolated Systolic Hypertension Among Middle-Aged and Elderly US Hypertensives

et al. 2001

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“…Current treatment often focuses on lowering vascular volume or reducing smooth muscle tone, which can reduce both systolic and diastolic pressures, resulting in less fall in PP and suboptimal therapeutic benefit. 13,15,16 Nitrates can selectively affect systolic pressures, 36 although hysteresis and other factors have limited their use. ACE inhibitors, calciumchannel blockers, and nonpharmacological interventions such as exercise also improve large vessel compliance [37][38][39] ; however the independence of these effects from mean pressure is less certain.…”

Section: Clinical Implications and Future Directionsmentioning

confidence: 99%

“…Current antihypertensive therapies focus on the first 3 factors, 13,15 yet this can run the risk of reducing diastolic pressure while inadequately lowering PP. 13,[15][16][17] Treatments targeting structural factors remain largely unexplored. Among the latter are alterations in matrix proteins within the vessel wall from nonenzymatic crosslinks between glucose (or other reducing sugars) and amino groups that generate advanced glycation end-products (AGE).…”

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confidence: 99%

Improved Arterial Compliance by a Novel Advanced Glycation End-Product Crosslink Breaker

et al. 2001

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Background-Arterial stiffening with increased pulse pressure is a leading risk factor for cardiovascular disease in the elderly. We tested whether ALT-711, a novel nonenzymatic breaker of advanced glycation end-product crosslinks, selectively improves arterial compliance and lowers pulse pressure in older individuals with vascular stiffening. Methods and Results-Nine US centers recruited and randomly assigned subjects with resting arterial pulse pressures Ͼ60 mm Hg and systolic pressures Ͼ140 mm Hg to once-daily ALT-711 (210 mg; nϭ62) or placebo (nϭ31) for 56 days. Preexisting antihypertensive treatment (90% of subjects) was continued during the study. Morning upright blood pressure, stroke volume, cardiac output, systemic vascular resistance, total arterial compliance, carotid-femoral pulse wave velocity, and drug tolerability were assessed. ALT-711 netted a greater decline in pulse pressures than placebo (Ϫ5.3 versus Ϫ0.6 mm Hg at day 56; Pϭ0.034 for treatment effect by repeated-measures ANOVA). Systolic pressure declined in both groups, but diastolic pressure fell less with ALT-711 (Pϭ0.056). Mean pressure declined similarly in both groups (Ϫ4 mm Hg; PϽ0.01 for each group, Pϭ0.34 for treatment effect). Total arterial compliance rose 15% in ALT-711-treated subjects versus no change with placebo (Pϭ0.015 versus ALT-711), an effect that did not depend on reduced mean pressure. Pulse wave velocity declined 8% with ALT-711 (PϽ0.05 at day 56, Pϭ0.08 for treatment effect). Systemic arterial resistance, cardiac output, and heart rate did not significantly change in either group. Conclusions-ALT-711 improves total arterial compliance in aged humans with vascular stiffening, and it may provide a novel therapeutic approach for this abnormality, which occurs with aging, diabetes, and isolated systolic hypertension.

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“…8 Patients with hypertension often have hypertrophy and reduced compliance in the conduit arteries, which may be related to an increased amount of collagen in the vessel wall, 9 thereby predisposing to increased levels of circulating collagen markers in the blood. Furthermore, antihypertensive treatment known to increase compliance and reduce vascular hypertrophy 10 may also reduce vascular fibrosis. 11 The 'Losartan Intervention For EndpointReduction in Hypertension' (LIFE) trial, 12 which was an intervention study testing the effect of losartan-vs atenolol-based antihypertensive treatment on cardiovascular events, included patients with hypertension and electrocardiopgraphic LV hypertrophy having higher risk of myocardial fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Markers of collagen synthesis is related to blood pressure and vascular hypertrophy: a LIFE substudy

et al. 2005

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Cardiac fibrosis and high levels of circulating collagen markers has been associated with left ventricular (LV) hypertrophy. However, the relationship to vascular hypertrophy and blood pressure (BP) load is unclear. In 204 patients with essential hypertension and electrocardiographic LV hypertrophy, we measured sitting BP, serum collagen type I carboxy-terminal telopeptide (ICTP) reflecting degradation, procollagen type I carboxy-terminal propeptide (PICP) reflecting synthesis and LV mass by echocardiography after 2 weeks of placebo treatment and after 1 year of antihypertensive treatment with a losartan-or an atenolol-based regimen. Furthermore, we measured intima-media thickness of the common carotid arteries (IMT), minimal forearm vascular resistance (MFVR) by plethysmography and ambulatory 24-h BP in around half of the patients. At baseline, PICP/ICTP was positively related to IMT (r ¼ 0.24, Po0.05), MFVR men (r ¼ 0.35, Po0.01), 24-h systolic BP (r ¼ 0.24, Po0.05) and 24-h diastolic BP (r ¼ 0.22, Po0.05), but not to LV mass. After 1 year of treatment with reduction in systolic BP (175715 vs 151717 mmHg, Po0.001) and diastolic BP (9978 vs 8879 mmHg, Po0.001), ICTP was unchanged (3.771.4 vs 3.871.4 lg/l, NS) while PICP (121739 vs 102729 lg/l, Po0.001) decreased. The reduction in PICP/ICTP was related to the reduction in sitting diastolic BP (r ¼ 0.31, Po0.01) and regression of IMT (r ¼ 0.37, Po0.05) in patients receiving atenolol and to reduction in heart rate in patients receiving losartan (r ¼ 0.30, Po0.01). In conclusion, collagen markers reflecting net synthesis of type I collagen were positively related to vascular hypertrophy and BP load, suggesting that collagen synthesis in the vascular wall is increased in relation to high haemodynamic load in a reversible manner.

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

Cited by 33 publications

References 71 publications

Predominance of Isolated Systolic Hypertension Among Middle-Aged and Elderly US Hypertensives

Predominance of Isolated Systolic Hypertension Among Middle-Aged and Elderly US Hypertensives

Improved Arterial Compliance by a Novel Advanced Glycation End-Product Crosslink Breaker

Markers of collagen synthesis is related to blood pressure and vascular hypertrophy: a LIFE substudy

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