Serum carboxymethyl-lysine, an advanced glycation end product, is associated with increased aortic pulse wave velocity in adults.

Cardiovascular diseases are the leading cause of morbidity and mortality in industrialized countries. Aging of the arterial system is characterized by decreased elasticity, diffuse intimal thickening, endothelial dysfunction, and accumulation of vascular interstitial collagen.1 The conduit arteries provide a low resistance path for the blood supply to the visceral organs and limbs, and the compliant nature of the aorta and carotid arteries provide a buffering function by expanding to accommodate the blood ejected by the left ventricle during systole.2 With normal elasticity of the conduit arteries, the pressure wave reflected from the periphery returns to the heart during diastole. In middle-aged adults with increased arterial stiffness, the velocity of the pressure wave increases, and the reflected pressure wave reaches the heart during late-systole.3 In older adults, the reflected pressure wave arrives earlier in systole, leading to increased systolic pressure, elevated cardiac afterload, and decreased diastolic blood pressure that potentially compromises coronary blood flow.4 Increased arterial stiffness is associated with hypertension and is predictive of coronary heart disease, stroke,5 and cardiovascular mortality.1,4 The factors that contribute to the pathophysiology of arterial stiffness have been incompletely characterized. Advanced glycation end products (AGEs), bioactive molecules formed by the non-enzymatic glycation of proteins, lipids, and nucleic acids, accumulate in arteries with age6 and increase vascular stiffness by inducing collagen cross-linking in the vessel wall, at least in diabetic rats.7 In animal models, treatment with alagebrium (formerly ALT7-111), a thiazolium derivative that can break established AGE cross-links, reversed the arterial stiffness associated with diabetes,8 reversed age-related increases in myocardial stiffness, improved cardiac function, and reduced the upregulation of collagen in the myocardium.9 In old, healthy, nondiabetic rhesus monkeys, treatment with alagebrium reduced arterial stiffness, as measured by aortic pulse wave velocity and augmentation index of the carotid arterial pressure waveform, and improved cardiac function.10 In phase 2 trials, alagebrium improved arterial compliance in elderly patients with vascular stiffening11 and improved cardiac function in older adults with diastolic heart failure.12 A recent prospective study showed that moderately to severely disabled older community-dwelling women with elevated serum AGEs were at increased risk of dying from cardiovascular disease.13 Although AGEs may be related to cardiovascular mortality in the general population, the biological mechanisms that might explain this association are unclear. Previous studies of AGEs and arterial stiffness have been conducted in highly selected patients with hypertension14 or diabetes.15 We postulated that elevated serum AGEs are associated with increased aortic pulse wave velocity, a measure of arterial stiffness, in older adults. To address this hypothesis, we examined the relation between serum advanced glycation end products and aortic pulse wave velocity in community-dwelling adults.