Alterations in arterial wall function and structure precede atherosclerosis and cardiovascular events. Endothelial dysfunction is the earliest marker of these changes.78
Pharmacological treatment of hypertension has reduced CVA to predicted levels but CHD reduction has been sub-optimal. This “CHD Gap” may be due to lack of therapeutic response in improving:
- endothelial dysfunction
- arterial compliance
- concomitant risk factors
- hemodynamic and hypertension dysfunction
Endothelial dysfunction effects arterial compliance via nitric oxide
Arteries have a “buffering capacity” where they expand during systole but then constrict during diastole. This provides the effect of an additional pump maintaining the flow of blood. Compliant arteries have good buffering capacity.
During systole there is a rapid infusion of blood from the stroke volume being pumped out from the heart. 20-30% is forward flow and 70-80% is stored in the large conduit (capacitive) arteries then released during diastole. This buffering capacity converts the pulsatile flow in the aorta to a more continuous flow in the capillaries (Windkessel effect).
Stiff arteries lose their buffering capacity. The loss of buffering that occurs with decreased arterial compliance reduces continuous flow but increased pulsatile flow to precapillary and capillary vasculature. The increased pulsatile flow induces small vessel damage, end organ dysfunction and damage.
This results in increased systolic blood pressure, decreased diastolic blood pressure, increased pulse pressure, left ventricular hypertrophy, and increased pressure transmission to the smaller arteries resulting in arteriolar damage. Decreased arterial compliance causes an out of phase propagation of flow and pressure waves which are faster and more distorted. There is also a reflected wave resulting in an augmented pressure (augmentation index).
The structure of the artery determines vascular compliance (stiffness).
Types of arteries:
- Conduit (capacitive): C1. Conduit arteries store blood in systole and buffer the pressure. They have a thin endothelium with thick layers of elastin and collagen. Less vascular smooth muscle.
- Branch (oscillatory): C2. Pressure oscillations & reflected waves. They consist of intermediate structure.
- Arterioles (Resistance): C2. These control blood flow. Vascular smooth muscle and endothelium primarily with minimal elastin or collagen. They are NO dependent and an early marker of vascular disease (hypertension, hyperlipidemia, and diabetes). The role of the endothelium is greatest in thin wall vessels (oscillatory and resistance). Endothelial dysfunction occurs earliest and has the greatest effect in C2 vessels.
Vascular remodeling – see post
arterial compliance: Measurement
Noninvasive applanation tonometry – computerized arterial pulse waveform analysis (CAPWA)
- synthesize arterial pulse waveform analysis
- central hemodynamics improves: diagnosis, monitoring, prognosis
- index of wave augmentation: arterial stiffness, vascular load, wave reflection, coronary perfusion
- evaluated therapy central vs peripheral pressure discrepancies
- increased pulse wave velocity correlates with increased 24 hour heart, especially after 50 years of age
- pulse wave velocity is an independent risk factor for cardiovascular disease in hypertension
Vascular wall function, CVD, and Hypertension
- Concept of risk marker vs risk contributor: blood pressure is both
- Blood pressure as a risk marker: systolic blood pressure – decreased C1 compliance, increased left ventricular hypertrophy, decreased aortic storage capacity, ISH, increased coronary heart disease, CVA, renal risk >> DBP, nocturnal blood pressure dipping, pulse pressure
Arterial Compliance: Structure/Function: Treatment
- Human trials with gluteal artery biopsies to assess vascular wall structure and function
- Correct both structure and function
- Increase small artery diameter, increase arterial compliance, decrease media/lumen ratio, decrease SVR and blood pressure
- Remodeling of arterioles: ACEi, ARB, CCB, DRI
- Nitroglycerin: increases arterial compliance; decreases pulse wave velocity; no change in systemic vascular resistance, distensibility, and EM
- Decreased systolic blood pressure, decreased pulse pressure (10%), no change in diastolic blood pressure
Antihypertensive Drug Effects on Apoptosis: ACEiARB & CCB
- decreased aortic cross sectional area and blood pressure
- increased DNA laddering
- increased BAX/Bcl-2 ratio
- increased BAX gene expression – apoptotic
- decreased Bcl-2 gene expression – anti-apoptotic
- Promote through apoptosis regression in vascular growth in hypertension
Arterial compliance, defined as a change in dimension in response to a given change in stress, is becoming an increasingly important clinical parameter. Related concepts, such as Distensibility, elasticity, and stiffness, and more traditional concepts such as resistance, afterload, and impedance need to be differentiated from compliance, although they are frequently (inappropriately) used interchangeably. Many studies cannot differentiate between compliance changes due to a drug’s effect on blood pressure and those due to a drug’s effect on vessel wall integrity.
This differentiation is important because a more physiologic therapy, one that benefits pulsatile and non-pulsatile flow, should be of greater clinical benefit than a therapy that only lowers blood pressure. A number of methods have been used to estimate compliance, but to date there is no generally agreed-on best method. There are longitudinal studies that relate abnormal compliance and drug effects to outcome. Patients at risk from a variety of disease states, such as hypertension, diabetes mellitus, and hypercholesterolemia, may benefit from earlier recognition of abnormal compliance. Earlier recognition may lead to interventions that would reduce their risk.
Loss of Elasticity is a Marker for Atherosclerotic Plaque Burden. Elasticity measurements can be used for identification of patients with diffuse atherosclerotic processes of the coronary arteries. Small Artery Elasticity was found to be an independent predictor of coronary artery status as assessed by angiogram.2 .
Loss of Small Artery Elasticity is Predictive of Cardiovascular Events. For every 2-unit decrease in C2-Small Artery Elasticity Index, there is a 50% increase in cardiovascular events (p < .001). Overall accuracy of C2-Small Artery Elasticity in predicting likelihood of cardiac events = 76.8%. Occurrence of events as a function of baselinearterial compliance: N=419 subjects, 1 to 7 year follow-up; End points: MI, stroke, TIA, angina, coronary or peripheral revascularization, coronary artery or peripheral bypass graft, death.3 .
Repeatability of Arterial Elasticity Assessments: Healthy subjects from 7 European sites. Intra-visit measurements taken 5 minutes apart differed by less than 3%. Inter-visit measurements taken 1-5 weeks later differed by less than 4%. Conclusion: Measurement of AE is highly reproducible despite the fact that BP and hemodynamic status was not identical.4 .
Small Artery Elasticity is a Sensitive Marker for Endothelial Dysfunction5 .
Mean Arterial Pressure
Pulse Wave Velocity
Brachial Artery Area1
Brachial Artery Compliance1
Augmentation Index %
Flow Mediated Vasodilatation
C2 Small Artery Elasticity
Systemic Vascular Resistance
1 – Measured using high-fidelity echo-tracking ultrasound
2 – Measured using HD’s CardioVascular Profiling System
American Society of Hypertension Emphasizing Need to Go Beyond Blood Pressure.6 2005 definition of hypertension from ASH:
– Vascular abnormalities are central to the identification and treatment of hypertension
– Need to identify where the patient is on the disease continuum to individualize assessment and treatment
– Need global cardiovascular disease risk assessment, need to go beyond lowering blood pressure
2007 ESH guidelines for treating hypertension now include vascular assessment
Who should get this test?
Male or females between the ages of 15 to 65 that have at least one risk factor of cardiovascular disease:
- family history of CV disease
- family history of obesity
- family history of diabetes
- family history of elevated cholesterol
- sedentary lifestyle
- family history of high blood pressure
- Schiffrin E, Intengan H. Vascular Remodeling in Hypertension – Roles of Apoptosis, Inflammation, and Fibrosis. Hypertension. 2001;38:581–587. https://doi.org/10.1161/hy09t1.096249
- Syeda, B. et al, Arterial Compliance: A Diagnostic Marker for Atherosclerotic Plaque Burden?, American Journal of Hypertension, 16:356-362, 2003, ( U of Vienna, Austria) Ref: 197
- Grey, E. et.al, Small But Not Large Artery Compliance Predicts Cardiovascular Events, American Journal of Hypertension 16(No. 4), 265-269, 2003, (U of MN) Ref: 172
- Zimlichman, R. et. al, Determination of Arterial Compliance Using Blood Pressure WaveformAnalysis with the CR-2000 System, American Journal of Hypertension 18 (No.1):65-71, 2005
- Gilani, M et al., Role of nitric oxide deficiency and its detection as a risk factor in prehypertension, Journal of the American Society of Hypertension 1(No. 1), 45-55, 2007; Ref 261
- Giles, T. et.al, Expanding the Definition and Classification of Hypertension, The Journal of Clinical Hypertension 7 (No. 9):505-512, Ref. 229A