Photoplethysmographic assessment of pulse wave reflection: blunted response to endothelium-dependent beta2-adrenergic vasodilation in type II diabetes mellitus.

OBJECTIVES: We sought to determine whether a simple index of pressure wave reflection may be derived from the digital volume pulse (DVP) and used to examine endothelium-dependent vasodilation in patients with type II diabetes mellitus. BACKGROUND: The DVP exhibits a characteristic notch or inflection point that can be expressed as percent maximal DVP amplitude (IP(DVP)). Nitrates lower IP(DVP), possibly by reducing pressure wave reflection. Response of IP(DVP) to endothelium-dependent vasodilators may provide a measure of endothelial function. METHODS: The DVP was recorded by photoplethysmography. Albuterol (salbutamol) and glyceryl trinitrate (GTN) were administered locally by brachial artery infusion or systemically. Aortic pulse wave transit time from the root of the subclavian artery to aortic bifurcation (T(Ao)) was measured by simultaneous Doppler velocimetry. RESULTS: Brachial artery infusion of drugs producing a greater than threefold increase in forearm blood flow within the infused limb was without effect on IP(DVP), whereas systemic administration of albuterol and GTN produced dose-dependent reductions in IP(DVP). The time between the first and second peak of the DVP correlated with T(Ao) (r = 0.75, n = 20, p < 0.0001). The effects of albuterol but not GTN on IP(DVP) were attenuated by N(G)-monomethyl-L-arginine. The IP(DVP) response to albuterol (400 microg by inhalation) was blunted in patients with type II diabetes mellitus as compared with control subjects (fall 5.9 +/- 1.8% vs. 11.8 +/- 1.8%, n = 20, p < 0.02), but that to GTN (500 microg sublingually) was preserved (fall 18.3 +/- 1.2% vs. 18.6 +/- 1.9%, p = 0.88). CONCLUSIONS: The IP(DVP) is influenced by pressure wave reflection. The effects of albuterol on IP(DVP) are mediated in part through the nitric oxide pathway and are impaired in patients with type II diabetes.

Relation between number of cardiovascular risk factors/events and noninvasive Doppler ultrasound assessments of aortic compliance.

The aim of this study was to establish the relation between noninvasive Doppler ultrasound assessments of aortic compliance, based on "foot-to-foot" aortic pulse wave velocity measurements, and presumed atherosclerotic load in patients with vascular disease and/or diabetes mellitus. One hundred ten patients with vascular disease and/or diabetes mellitus (arteriopaths) underwent measurement of in vivo aortic compliance using Doppler ultrasound. Demographic data on these subjects were recorded along with details of cardiovascular risk factors and events. Aortic compliance values were compared with data from 51 age-matched healthy, asymptomatic subjects putatively free of vascular disease (controls). Data are expressed as mean+/-SD. Arteriopaths were aged 64.1+/-8.4 years and had total cholesterol levels of 5.9+/-1.1 mmol/L and aortic compliance of 0.78+/-0.42%/10 mm Hg [1.33 kPa]. Most arteriopaths had 2 or more cardiovascular risk factors and events: diabetes (n=41), hypertension (n=45), smoking (n=86), cerebrovascular/transient ischemic event (n=13), myocardial infarction (n=44), angina (n=51), and/or peripheral vascular disease (n=33). Controls were aged 64.3+/-12.1 years with total cholesterol of 6.1+/-1.1 mmol/L and aortic compliance of 1.14+/-0.46%/10 mm Hg [1.33 kPa] (P<0.002 versus arteriopaths). Subset analysis revealed that patients with the greatest number of cardiovascular risk factors and events (n=5) had the stiffest aortas (aortic compliance, 0.58+/-0.15%/10 mm Hg [1.33 kPa]) compared with those patients with the median and mean (n=2) number of risk factors and events (aortic compliance, 0.80+/-0.50%/10 mm Hg [1.33 kPa]; P<0.02). The data suggest that a significant inverse relation exists between presumed atherosclerotic load (as assessed by the number of cardiovascular risk factors and events) and aortic compliance determined noninvasively based on aortic pulse wave velocity measurements. If these findings are confirmed by prospective, longitudinal follow-up studies, such measurements may prove useful as a noninvasive marker of vascular risk.

Ethnicity affects IGFBP-3 and IGF-II in normal healthy young adult subjects.

OBJECTIVE: While the effects of age on the growth hormone/insulin-like growth factor (IGF) axis are well documented, the influence of ethnic background is unknown. The differences in IGF and IGF binding proteins (IGFBPs) were investigated in two ethnic groups. DESIGN: A cross-sectional study of an age-selected cohort of healthy, normoglycaemic, non-obese Caucasian (C) and Asian (A) subjects. PATIENTS: Fifty-three (27 C, 26 A) subjects with a mean age (+/- SD) of 20.6 +/- 0.8 years were studied. MEASUREMENTS: Fasting measurements of glucose, insulin, IGF-I, IGF-II, IGFBP-1 and IGFBP-3. Western ligand blotting and immunoblotting with IGFBP-2 and IGFBP-3 of serum samples. RESULTS: There were no significant differences in IGF-I levels between Caucasian and Asian subjects (C 218 +/- 55 vs A 229 +/- 40 micrograms/l; P = 0.44). IGF-II (C 707 +/- 110 vs A 583 +/- 75 micrograms/l; P < 0.0001) and IGFBP-3 (C 5.9 +/- 1.2 vs A 5.12 +/- 1.17 mg/l; P = 0.01) levels were significantly higher in Caucasian subjects. Immunoblotting of ligand blots revealed no protease activity on either IGFBP-3 or IGFBP-2 to account for these ethnic differences. CONCLUSIONS: Ethnic differences in IGFBP-3 and associated IGF-II levels may affect the inter-relationships of IGFs and their binding proteins and need to be considered when interpreting IGF data on growth and metabolism.

A family history of NIDDM is associated with decreased aortic distensibility in normal healthy young adult subjects.

OBJECTIVE: NIDDM is associated with stiffer arteries and an increased incidence of macrovascular disease. NIDDM has strong familial inheritance. We studied the associations of a family history of NIDDM with blood pressure-corrected aortic distensibility (Cp). RESEARCH DESIGN AND METHODS: Because age is a strong determinant of arterial distensibility, we studied an age-select cohort of 67 healthy normotensive normoglycemic young adults along with fasting measurements of glucose and insulin concentrations. Cp was calculated from noninvasive Doppler ultrasound measurements of pulse wave velocity along the descending thoracoabdominal aorta. RESULTS: The mean age of the subjects was 20.6 +/- 0.7 (mean +/- SD) years. A total of 22 subjects gave a positive family history of NIDDM in a parent or grandparent. Subjects with a positive family history of NIDDM had significantly less distensible (i.e., stiffer) aortas than their age- and sex-matched counterparts who gave no family history of NIDDM (Cp [dimensionless]: 0.22 +/- 0.04 vs. 0.25 +/- 0.04, P = 0.02). Subjects with a positive family history of NIDDM also had significantly higher fasting glucose (5.1 +/- 0.4 vs. 4.9 +/- 0.4 mmol/l, P = 0.009) and insulin (7.5 +/- 5.5 vs. 4.2 +/- 2.0 mU/l, P = 0.02) levels and BMIs (23.2 +/- 2.3 vs 21.1 +/- 2.5 kg/m2, P = 0.002). On multivariate regression analysis, family history of NIDDM (P = 0.03) was the only significant independent predictor of Cp. CONCLUSIONS: A positive family history of NIDDM is associated with decreased aortic distensibility in early adult life. The relevance of these observations to future cardiovascular events merits further investigation.

Aortic distensibility in patients with cerebrovascular disease.

1. Non-invasive aortic compliance measurements have been used previously to assess the distensibility of the aorta in several pathological conditions associated with increased cardiovascular risk. We set out to establish whether aortic compliance is abnormal in patients with stroke. 2. Pulse wave velocity measurements of thoraco-abdominal aortic compliance were made in 20 stroke patients and 25 age- and sex-matched hospitalized, non-stroke control subjects putatively free of cardiovascular disease. Since compliance varies with non-chronic changes in blood pressure, a blood pressure corrected index of aortic distensibility, Cp, was calculated. 3. Aortic compliance was significantly reduced in patients with stroke compared with non-stroke control subjects (0.46 +/- 0.27 versus 0.86 +/- 0.34%/10 mmHg, P < 0.0002), corresponding with higher values for pulse wave velocity. Stroke patients also had significantly higher systolic and diastolic blood pressures (P < 0.02 and P < 0.002 respectively) and total cholesterol levels (P < 0.004) than the control subjects. Calculation of Cp did not alter the observation of stiffer aortas in the stroke cohort (P < 0.0007). 4. In both stroke patient and control cohorts, as expected, inverse trends were observed between aortic compliance and blood pressure. Also as expected, in the control group Cp values did not show a relationship with blood pressure (r = 0.02, P = 0.092, not significant). However, in the stroke cohort a marked dependence of Cp on blood pressure was observed (r = -0.48, P = 0.03). 5. Transoesophageal echocardiographic studies have recently identified advanced atherosclerosis in the ascending aorta as a possible source of cerebral emboli and an independent risk factor for ischaemic stroke.(ABSTRACT TRUNCATED AT 250 WORDS)