production in humans. We further examined the effects of breakfast on these measures. Methods-We studied 42 healthy males (mean age: 34+1 years; BMI: 28?1 kg/m2). All subjects underwent complete overnight polysomnograhy during the study to confirm good sleep quality. ADMA, L-arginine, and NO levels were measured in all 42 subjects first before sleep (at 9 PM), and then immediately after awakening in the morning (at 6 AM). Twentyone subjects then ate a high-protein breakfast at 7 AM, soon after awakening, whereas the remaining 21 subjects continued fasting during the morning hours. A third measurement of ADMA, L-arginine. and NO was obtained in all 42 subjects at 11 AM. Results-Overnight, ADMA levels increased and L-arginine decreased, leading to a marked reduction in the L-arginine/ADMA ratio from 21856 at 9 PM to 16956 after waking at 6 AM (P<O.OOOl). NO decreased overnight from 40'4 pmol/L at 9 PM to 2722 pmol/L at 6 AM (P<O.OOOl). The morning reduction in the L-arginine/ADMA ratio was reversed by 11 AM only in those 21 subjects who ate breakfast (177-C8 at 6 AM, 225-C8 at 11 AM; P=0.0002). In contrast, the L-arginine/ ADMA ratio did not recover by 11 AM in the 21 subjects who continued fasting after waking. The overnight decrease in NO was also restored by ll AM only in those subjects who ate breakfast, in whom NO increased by 37% by 11 AM, whereas in those subjects who continued fasting, the low early morning NO levels at 6 AM fell even further, by 15% at 11 AM. Conclusions-Elevated ADMA, decreased L-arginine, low L-arginine/ADMA ratio, and reduced NO levels in the early morning after waking from sleep may be an important mechanism underlying the early morning peak in cardiovascular events. The morning decline in both the L-arginine/ADMA ratio and in NO can be prolonged and potentiated by fasting and attenuated by breakfast.

The resting ankle-brachial index (ABI) is a non-invasive method to assess the patency of the lower extremity arterial system and to screen for the presence of peripheral occlusive arterial disease. To determine how the ABI is associated with clinical coronary heart disease (CHD), stroke, preclinical carotid plaque and far wall intimal-medial thickness (IMT) of the carotid and popliteal arteries, we conducted analyses in 15 106 middle-aged adults from the baseline examination (1987–1989) of the Atherosclerosis Risk in Communities (ARIC) Study. The prevalence of clinical CHD, stroke/transient ischemic attack (TIA) and preclinical carotid plaque increased with decreasing ABI levels, particularly at those of <0.90. Individuals with ABI<0.90 were twice as likely to have prevalent CHD as those with ABI>0.90 (age-adjusted odds ratio (OR) ranging from 2.2 (95% CI: 1.0–5.1) in African-American men to 3.3 (95% CI: 2.1–5.0) in white men). Men with ABI<0.90 were more than four times as likely to have stroke/TIA as those with ABI>0.90 (age-adjusted OR: 4.2 (95% CI: 1.8–9.5) in African-American men and 4.9 (95% CI: 2.6–9.0) in white men). In women the association was weaker and not statistically significant. Among those free of clinical cardiovascular disease, individuals with ABI≤0.90 had statistically significantly higher prevalence of preclinical carotid plaque compared to those with ABI>0.90 (age-adjusted ORs ranging from 1.5 (95% CI: 1.0–1.9) in white women to 2.6 (95% CI: 1.06.6) in african-american men). The ABI was also inversely associated with far wall IMT of the carotid arteries (in both men and women) and the popliteal arteries (in men only). The associations of ABI with clinical CHD, stroke, preclinical carotid plaque and IMT of the carotid and popliteal arteries were attenuated and often not statistically significant after further adjustment for LDL cholesterol, cigarette smoking, hypertension and diabetes. These data demonstrate that low ABI levels, particularly those of <0.90, are indicative of generalized atherosclerosis.

Carotid sonography is being performed on more than 5,000 participants in the Cardiovascular Health Study, a prospective, multicenter study of cardiovascular disease in men and women aged 65 years and older. The sonographic methods used to examine and measure the extracranial carotid arteries are described. Initial validation studies were performed on 61 subjects with a mean age of 68.6 years. Analysis of within- and between-sonographer differences and between-reader differences were performed for selected variables. In general, the mean absolute differences for within- and between-sonographer comparisons were small, with even less variability between readers. Variability was less for the common carotid artery than for the internal carotid artery. These data suggest that carotid sonography is a reliable and reproducible method for use in the study of carotid atherosclerosis in population studies.

Carotid sonography is being performed on more than 5,000 participants in the Cardiovascular Health Study, a prospective, multicenter study of cardiovascular disease in men and women aged 65 years and older. The sonographic methods used to examine and measure the extracranial carotid arteries are described. Initial validation studies were performed on 61 subjects with a mean age of 68.6 years. Analysis of within- and between-sonographer differences and between-reader differences were performed for selected variables. In general, the mean absolute differences for within- and between-sonographer comparisons were small, with even less variability between readers. Variability was less for the common carotid artery than for the internal carotid artery. These data suggest that carotid sonography is a reliable and reproducible method for use in the study of carotid atherosclerosis in population studies.