Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension.

OBJECTIVES: Arterial stiffening and endothelial dysfunction are hallmarks of aging, and advanced glycation endproducts (AGE) may contribute to these changes. We tested the hypothesis that AGE crosslink breakers enhance endothelial flow-mediated dilation (FMD) in humans and examined the potential mechanisms for this effect. METHODS: Thirteen adults (nine men, aged 65 +/- 2 years) with isolated systolic hypertension (systolic blood pressure > 140 mmHg, diastolic blood pressure < 90 mmHg or pulse pressure > 60 mmHg) on stable antihypertensive therapy were studied. Subjects received placebo (2 weeks) then oral alagebrium (ALT-711; 210 mg twice a day for 8 weeks). Subjects and data analyses were blinded to treatment. Arterial stiffness was assessed by carotid augmentation index (AI) and brachial artery distensibility (ArtD) using applanation tonometry and Doppler echo, and endothelial function by brachial FMD. Serum markers of collagen metabolism and vascular inflammation were assessed. RESULTS: Alagebrium reduced carotid AI by 37% (P = 0.007) and augmented pressure (16.4 +/- 10 to 9.6 +/- 9 mmHg; P < 0.001). Heart rate, arterial pressures, and ArtD, were unchanged. FMD increased from 4.6 +/- 1.1 to 7.1 +/- 1.1% with alagebrium (P < 0.05), and was unrelated to altered shear stress or regional arterial distensibility. However, FMD change was inversely related to markers of collagen synthesis, p-selectin and intracellular cell adhesion molecule (all P < 0.05). Alagebrium-associated changes in plasma nitrite plus nitrate was inversely correlated with plasma matrix metalloproteinase 9 and type I collagen (P = 0.007). CONCLUSIONS: Alagebrium enhances peripheral artery endothelial function and improves overall impedance matching. Improved endothelial function correlates better with reduced vascular fibrosis and inflammation markers than with vessel distensibility. AGE-crosslink breakers may reduce cardiovascular risk in older adults by reduced central arterial stiffness and vascular remodeling.

Team care: beyond open and closed intensive care units.

PURPOSE OF REVIEW: Evidence supporting dedicated intensivist staffing in intensive care units is growing. Despite clinical and economic benefits, medical staff politics and a shortage of intensivists impede the intensivist model. The purpose of this paper is to accelerate patient's exposure to the benefits of intensivists, and introduce team care in the intensive care unit. RECENT FINDINGS: The cost savings achieved through intensivist staffing range from $510,000 to $3.3 million. The intensivist model may only have been adopted by 4% of intensive care units. Barriers to implementing the model are shortage of intensivists, reimbursement for intensivists, and political will. Four attributes make the model ideal: physical presence, knowledge of critical care practice, coordination of team care, and unit management. It may be helpful to not label intensive care units as open or closed and consider team care, whereby hospitals seek to achieve the attributes of the model given their resources and culture. SUMMARY: Intensivists save lives and costs. By working toward team care, hospitals may achieve a successful intensivist model, and patients may realize the benefits of spending less for healthcare and living longer. To achieve this model, physician and hospital leaders must form a partnership.