Stanley M. Finkelstein

Noninvasive Pulse Wave Analysis for the Early Detection of Vascular Disease

A noninvasive technique has been developed and validated for calculating capacitive and oscillatory systemic arterial compliance with the use of pulse wave analysis and a modified Windkessel model. Application of the technique to subjects with hypertension, postmenopausal women with symptomatic coronary artery disease, and appropriate control subjects has confirmed a reduction of oscillatory compliance in the disease states and an increase in capacitive and oscillatory compliances in response to vasodilator drugs. This method should be useful in screening subjects for early evidence of vascular disease and in monitoring the response to therapy.

Age-related abnormalities in arterial compliance identified by pressure pulse contour analysis : Aging and arterial compliance

The objective of this study was to evaluate age-related changes in pulsatile arterial function. Aging alters arterial pulsatile function and produces consistent changes in the pressure pulse contour. A reduced systemic arterial compliance that can be derived from analysis of the pulse contour is regarded as the best clinical index of impaired pulsatile arterial function and may mark the presence of early vascular damage. We analyzed intra-arterial brachial artery waveforms in 115 healthy normotensive volunteers (83 men, 32 women) and radial artery waveforms obtained with the use of a calibrated tonometer device in 212 healthy volunteers (147 women, 65 men). A computer-based assessment of the diastolic pressure decay and a modified Windkessel model of the circulation were used to quantify changes in arterial waveform morphology in terms of large artery or capacitive compliance, oscillatory or reflective compliance in the small arteries, inertance, and systemic vascular resistance. Large artery compliance and oscillatory compliance correlated negatively with age for both invasive and noninvasive groups (r=-0.50 and r=-0.55; r=-0.37 and r=-0.66; P<0.001 for all). The slopes of the regression lines for the decline in oscillatory compliance with age were significantly steeper than those recorded for large artery compliance estimates. The change in blood pressure with age independently contributed to the decrease in large artery compliance but not oscillatory compliance in both groups. Consistent age-related changes were found in the pressure pulse contour by analysis of waveforms obtained invasively or noninvasively from the upper limb. The change in the oscillatory or reflective compliance estimate was independent of blood pressure change and may represent a better marker than large artery or capacitive compliance of the degenerative aging process in altering pulsatile arterial function.

Diabetes mellitus associated with cystic fibrosis

The prevalence of overt diabetes mellitus and carbohydrate intolerance was studied in 448 patients with cystic fibrosis (CF). Insulin-dependent diabetes (IDDM) developed in 7.6% of patients (13 male and 21 female). Survival was significantly lower (P less than 0.01) in the IDDM-CF group, with fewer than 25% surviving to age 30 years, whereas nearly 60% of the nondiabetic CF population reached this age. A significant deterioration in CF clinical status, based on NIH score, became apparent 2 years before onset of overt IDDM (P less than 0.05 at 2 years prior, P less than 0.01 at IDDM diagnosis). Total glycosylated hemoglobin (HbA1) was significantly (P less than 0.001) higher for the total CF population (7.3% +/- 1.2%) than for the general non-CF population (6.5% +/- 0.7%), and in the IDDM-CF group (P less than 0.05) compared with normoglycemic CF control patients. Female patients had a higher mean HbA1 after 12 years of age than their male counterparts did (P less than 0.02). HBA1 did not predict the development of IDDM, but there was a weak inverse relationship between HbA1 and both NIH clinical score (r = -0.41, P less than 0.02) and standard pulmonary function tests (forced vital capacity, r = -0.25, P less than 0.01) in the general CF population. Therefore, impaired carbohydrate tolerance in CF is associated with progressive clinical deterioration.

Reduced small artery but not large artery elasticity is an independent risk marker for cardiovascular events

BACKGROUND Atherosclerosis begins in the arterial wall, with endothelial dysfunction accompanied by functional and structural changes that influence arterial stiffness. Pulse contour analysis provides an assessment of compliance or elasticity of the large conduit arteries (C(1)) and small microcirculatory arteries (C(2)). In this study, the predictive value of reduced elasticity of these arteries was evaluated by follow-up of subjects who underwent pulse contour analysis at the University of Minnesota. METHODS Questionnaires were sent to 870 subjects who had radial artery pulse wave analysis performed between 1993 and 1999 using a noninvasive sensor, parameter estimating algorithm and modified Windkessel model of the circulation. Responses from 419 subjects >19 years of age reported on any cardiovascular events including death, myocardial infarction, stroke, transient ischemic attacks, angina, or coronary or peripheral vascular interventional procedures. RESULTS Of the subjects, 168 (41%) reported one or more cardiovascular events. Events were more common in those with elevated blood pressure, elevated cholesterol, diabetes, and family history of events. Age, reduced C(1), and reduced C(2) were univariate predictors of events. After adjusting for age, a 2-unit decrease in C(2) remained a significant predictor (odds ratio 1.50, P <.001), whereas C(1) was no longer predictive. CONCLUSION Reduced small artery elasticity, which is a measure of endothelial dysfunction, is significantly associated with cardiovascular events independent of age.

First- and third-order models for determining arterial compliance

BACKGROUND Engineering models of the arterial vasculature have been used to describe vascular properties of resistance and compliance. These approaches have used either Fourier frequency analysis, based on transmission line equations, or time domain analysis of the circuit equations describing modified Windkessel models of the vasculature. DESIGN A third-order, four-element modified Windkessel model can reproduce arterial pressure waveforms, including both exponential and oscillatory pressure decays observed during the diastolic portion of the cardiac cycle. METHOD A method to determine both capacitive and oscillatory compliance of the arterial vasculature was developed, and the effect of these compliance properties on the blood pressure waveform was examined.

Vascular abnormalities in non-insulin-dependent diabetes mellitus identified by arterial waveform analysis

PURPOSE The arterial pressure waveform is derived from the complex interaction of the left ventricular stroke volume and the physical properties of the arterial circulation. Widespread abnormalities in the physical characteristics of the arterial vessels associated with diabetes mellitus can produce consistent changes in the shape of the pressure pulse waveform, providing information about arterial structure and tone that can be quantitated by pulse contour analysis. PATIENTS AND METHODS We analyzed intraarterial brachial artery waveforms in 28 patients with non-insulin-dependent diabetes mellitus and 22 control subjects matched for age and sex. A computer-based assessment of the diastolic pressure decay and a modified Windkessel model of the circulation were employed to quantify changes in arterial waveform morphology in terms of the large-artery compliance (C1), the oscillatory diastolic waveform (C2), inertance, and systemic resistance. RESULTS No differences were found in heart rate, mean arterial pressure, cardiac output, or stroke volume between groups. The mean oscillary arterial compliance estimate was significantly reduced in diabetic subjects versus controls: 0.02 (95% confidence interval [CI], 0.01 to 0.03) mL/mm Hg versus 0.08 (95% CI, 0.04 to 0.12) mL/mm Hg (p < 0.001). Oscillatory compliance values were uniformly reduced in the diabetic subjects regardless of the presence or absence of physical complications of the disease. No differences in large-artery compliance, inertance, or systemic resistance were found between groups. No positive correlations were found between indices of glycemic control, the known duration of diabetes, and any of the hemodynamic variables. CONCLUSIONS Quantitative changes in the arterial pressure pulse waveform, reflected by a reduced oscillatory compliance estimate, were found in patients with non-insulin-dependent diabetes mellitus. This estimate appears to act as an early marker for the vascular abnormalities associated with diabetes before complications of the disease become clinically apparent. By contrast, no changes in large-artery compliance were found in this patient population free from clinically obvious macrovascular disease.

Vascular abnormalities associated with long-term cigarette smoking identified by arterial waveform analysis.

PURPOSE Consistent changes in the arterial pulse contour are found with aging and disease states that impair the compliance characteristics of blood vessels that buffer pulsatile phenomena in the arterial tree. We assessed whether vascular adaptation in structure or tone of blood vessels associated with long-term cigarette smoking would influence steady state or pulsatile hemodynamics at a preclinical stage. PATIENTS AND METHODS We analyzed intraarterial brachial artery waveforms in 35 healthy long-term cigarette smokers and 32 nonsmoking control subjects matched for age and gender. The diastolic pressure decay was segmented into two components: an exponential decay that reflects the compliance characteristics of the large arteries and an oscillatory diastolic waveform generated principally by pulse-wave reflections from small arteries and arterioles. RESULTS Resting heart rate was higher in smokers than nonsmokers, mean +/- SD (66 +/- 9 versus 60 +/- 10; P < 0.05). Systolic, diastolic, and mean arterial pressures were lower in smokers compared with nonsmokers (P < 0.01 for all). No differences in cardiac output, large artery compliance, or systemic vascular resistance estimates where apparent between groups. A decrease in the amplitude and duration of the diastolic wave, produced by peripheral pulse-wave reflections in the arterial system, was found in smokers compared with nonsmokers (0.04 +/- 0.02 versus 0.7 +/- 0.03; P < 0.001). CONCLUSIONS Quantitative changes in the arterial waveform were found in long-term smokers compared with nonsmoking control subjects. The altered arterial wave shape marks the presence of abnormal structure or tone in the peripheral vasculature that affects pulsatile arterial function. This measure of vascular injury is detectable at a preclinical stage and may relate to the subsequent risk of morbid events in chronic smokers and aid in clinical risk stratification.

Arterial vascular compliance response to vasodilators by Fourier and pulse contour analysis.

Vasodilator drugs are widely used in the management of cardiovascular disease. They decrease systemic vascular resistance, but they also may influence vascular arterial compliance. This study evaluated the effects of three vasodilators—nitroprusside, nltroglycerin, and hydralazine—on vascular compliance using impedance parameters determined by pulse contour and Fourier analyses. The open chest study was performed on anesthetized dogs. Mean arterial pressure decreased by a minimum of 20% after vasodilator intervention. The decrease in systemic vascular resistance was significant (p < 0.01) only after hydralazine treatment. Proximal compliance increased after administration of all drugs, but the increase was not statistically significant. Distal compliance determined by pulse contour analysis increased by 60 to 120% after all three drug treatments (p < 0.05 for nitroprusside, p < 0.02 for nitroglycerin and hydralazine). Characteristic impedance from Fourier analysis responded variably, and changes were not statistically significant. The sensitivity of changes in distal compliance as a marker for the vascular effect of these drugs suggests that it might be used as a more reliable guide than blood pressure or vascular resistance in monitoring clinical response to such intervention. The more traditional measure of characteristic impedance provides a vascular measurement that is less sensitive than distal compliance to the effects of these vasodilator drugs.

Arterial compliance abnormalities in isolated systolic hypertension.

Arterial compliance measurements using intraarterial pulse contour analysis and a modified Windkessel model were carried out in 19 patients with isolated systolic hypertension (> or = 160/< or = 90 mm Hg) and compared to measurements in 29 patients with essential hypertension (diastolic blood pressure [BP] > or = 95 mm Hg) and 47 normotensive control subjects. Arterial capacitive compliance was significantly lower in isolated systolic hypertension than in essential hypertension (P < .0002) and significantly lower in essential hypertension than in normotensive control subjects (P < .0001). Although the isolated systolic hypertension group was older than the essential hypertension group, the reduction of capacitive compliance in isolated systolic hypertension persisted even when comparison was made with a more nearly age-matched group of essential hypertension. In contrast, oscillatory compliance was reduced similarly in isolated systolic hypertension and essential hypertension compared to normotensive control subjects (P < .0001). Although pulse pressure was greater in isolated systolic hypertension than in essential hypertension, only a weak correlation (r = -0.34) existed between pulse pressure and capacitive compliance. These data indicate that both essential hypertension and isolated systolic hypertension patients exhibit comparably abnormal structure or tone of the small vessels that are the site of oscillations or reflections in the arterial vasculature. In isolated systolic hypertension there is a profound reduction in large artery or capacitive compliance that accounts for the increase in systolic BP and decrease in diastolic BP. This abnormality cannot be accurately assessed by pulse pressure alone.

Vascular hemodynamic impedance in congestive heart failure.

The objective of this study was to determine whether pulse-contour analysis could provide a measure of the differences in peripheral vascular state between patients with congestive heart failure (CHF) and healthy persons. Vascular hemodynamic impedance parameters were determined from brachial artery pressure waveforms recorded in 14 patients with CHF, aged 20 to 55 years (mean 36 +/- 12) and in 7 healthy control subjects, aged 22 to 55 years (mean 33 +/- 12). Cardiac output, heart sounds and electrocardiogram were also monitored. Cardiac output was 32% lower (p less than 0.01) and heart rate was 43% higher (p less than 0.001) in the CHF group than in the control group. The mean arterial pressure did not differ between groups. Systemic vascular resistance was 47% higher (p less than 0.05) and distal vascular compliance 73% lower (p less than 0.001) in the CHF group than in control group. Proximal vascular compliance was unchanged. These studies suggest that distal compliance assessed from pulse-contour analysis is a more sensitive and specific index than systemic vascular resistance to the vascular changes in CHF.