Measures of aortic stiffness and pressure and flow pulsatility have emerged as correlates of and potential contributors to cardiovascular disease, dementia, and kidney disease. Higher aortic ...stiffness and greater pressure and flow pulsatility are associated with excessive pulsatile load on the heart, which increases mass and reduces global longitudinal strain of the left ventricle. Excessive stiffness and pulsatility are also associated with microvascular lesions in high-flow organs, such as the brain and kidney, suggesting that small vessels in these organs are damaged by pulsatility. This brief review will summarize evidence relating aortic stiffness to cardiovascular, brain, and kidney disease.
Over the past decade, numerous studies have shown that increased aortic stiffness is associated with major cardiovascular disease end points, including heart disease, stroke, and kidney disease. ...Cardiac abnormalities and enhanced atherogenesis in the setting of increased pulsatile load on heart and arteries have been well described. However, recent studies have shown a further association between excessive pressure pulsatility and a number of afflictions of aging that share a predominant microvascular etiology, including many forms of kidney disease and cognitive impairment. In these disorders, microvascular remodeling and impaired regulation of local blood flow, which are related to large artery stiffness and pressure pulsatility, are associated with evidence of diffuse microscopic tissue damage. This brief review will summarize age-related changes in aortic and peripheral vascular function and will discuss potential mechanisms leading from changes in properties of large arteries to excessive pressure pulsatility, abnormal microvascular structure and function, and end-organ dysfunction and damage.
Arterial stiffness, a leading marker of risk in hypertension, can be measured at material or structural levels, with the latter combining effects of the geometry and composition of the wall, ...including intramural organization. Numerous studies have shown that structural stiffness predicts outcomes in models that adjust for conventional risk factors. Elastic arteries, nearer to the heart, are most sensitive to effects of blood pressure and age, major determinants of stiffness. Stiffness is usually considered as an index of vascular aging, wherein individuals excessively affected by risk factor exposure represent early vascular aging, whereas those resistant to risk factors represent supernormal vascular aging. Stiffness affects the function of the brain and kidneys by increasing pulsatile loads within their microvascular beds, and the heart by increasing left ventricular systolic load; excessive pressure pulsatility also decreases diastolic pressure, necessary for coronary perfusion. Stiffness promotes inward remodeling of small arteries, which increases resistance, blood pressure, and in turn, central artery stiffness, thus creating an insidious feedback loop. Chronic antihypertensive treatments can reduce stiffness beyond passive reductions due to decreased blood pressure. Preventive drugs, such as lipid-lowering drugs and antidiabetic drugs, have additional effects on stiffness, independent of pressure. Newer anti-inflammatory drugs also have blood pressure independent effects. Reduction of stiffness is expected to confer benefit beyond the lowering of pressure, although this hypothesis is not yet proven. We summarize different steps for making arterial stiffness measurement a keystone in hypertension management and cardiovascular prevention as a whole.
As far back as the ancient Egyptians and Greeks, physicians have observed and interpreted the arterial pulse to diagnose disease. In the last 20 years, advances in modern engineering have rendered ...quantitative pulse wave analysis widely available, reliable, and reproducible. To date, measurement of arterial stiffness has remained almost exclusively a research activity. However, ongoing technological improvements coupled with already strong and growing evidence of clinical value should facilitate integration of arterial stiffness measures into clinical practice in the near future. This brief review will highlight clinical areas where arterial stiffness measures are likely to be the most informative in clinical practice.
Vascular stiffness increases with advancing age and is a major risk factor for age-related morbidity and mortality. Vascular stiffness and blood pressure pulsatility are related; however, temporal ...relationships between vascular stiffening and blood pressure elevation have not been fully delineated.
To examine temporal relationships among vascular stiffness, central hemodynamics, microvascular function, and blood pressure progression.
Longitudinal community-based cohort study conducted in Framingham, Massachusetts. The present investigation is based on the 2 latest examination cycles (cycle 7: 1998-2001; cycle 8: 2005-2008 last visit: January 25, 2008) of the Framingham Offspring study (recruited: 1971-1975). Temporal relationships among blood pressure and 3 measures of vascular stiffness and pressure pulsatility derived from arterial tonometry (carotid-femoral pulse wave velocity CFPWV, forward wave amplitude FWA, and augmentation index) were examined over a 7-year period in 1759 participants (mean SD age: 60 9 years; 974 women).
The primary outcomes were blood pressure and incident hypertension during examination cycle 8. The secondary outcomes were CFPWV, FWA, and augmentation index during examination cycle 8.
In a multivariable-adjusted regression model, higher FWA (β, 1.3 95% CI, 0.5-2.1 mm Hg per 1 SD; P = .002) and higher CFPWV (β, 1.5 95% CI, 0.5-2.6 mm Hg per 1 SD; P = .006) during examination cycle 7 were jointly associated with systolic blood pressure during examination cycle 8. Similarly, in a model that included systolic and diastolic blood pressure and additional risk factors during examination cycle 7, higher FWA (odds ratio OR, 1.6 95% CI, 1.3-2.0 per 1 SD; P < .001), augmentation index (OR, 1.7 95% CI, 1.4-2.0 per 1 SD; P < .001), and CFPWV (OR, 1.3 95% CI, 1.0-1.6 per 1 SD; P = .04) were associated with incident hypertension during examination cycle 8 (338 cases 32% in 1048 participants without hypertension during examination cycle 7). Conversely, blood pressure during examination cycle 7 was not associated with CFPWV during examination cycle 8. Higher resting brachial artery flow (OR, 1.23 95% CI, 1.04-1.46) and lower flow-mediated dilation (OR, 0.80 95% CI, 0.67-0.96) during examination cycle 7 were associated with incident hypertension (in models that included blood pressure and tonometry measures collected during examination cycle 7).
In this cohort, higher aortic stiffness, FWA, and augmentation index were associated with higher risk of incident hypertension; however, initial blood pressure was not independently associated with risk of progressive aortic stiffening.
Obesity, hypertension, and diabetes are independently associated with cardiac remodeling and frequently co-cluster. The conjoint and separate influences of these conditions on cardiac remodeling have ...not been investigated.
We evaluated 5,741 Framingham Study participants (mean age 50 years, 55% women) who underwent echocardiographic measurements of left ventricular (LV) mass (LVM), LV ejection fraction (LVEF), global longitudinal strain (GLS), mitral E/e', left atrial end-systolic (peak) dimension (LASD) and emptying fraction (LAEF). We used multivariable generalized linear models to estimate the adjusted-least square means of these measures according to cross-classified categories of body mass index (BMI; normal, overweight and obese), hypertension (yes/no), and diabetes (yes/no).
We observed statistically significant interactions of BMI category, hypertension, and diabetes with LVM, LVEF, GLS, and LAEF (p for all 3-way interactions <0.01). Overweight and obesity (compared to normal BMI), hypertension, and diabetes status were individually and conjointly associated with higher LVM and worse GLS (p<0.01 for all). We observed an increase of 34% for LVM and of 9% for GLS between individuals with a normal BMI and without hypertension or diabetes compared to obese individuals with hypertension and diabetes. Presence of hypertension was associated with higher LVEF, whereas people with diabetes had lower LVEF.
Obesity, hypertension, and diabetes interact synergistically to influence cardiac remodeling. These findings may explain the markedly heightened risk of heart failure and cardiovascular disease when these factors co-cluster.
To examine the putative measures of arterial stiffness and the mechanisms of adverse effects of stiffness on blood pressure and target organ damage using data from comprehensive hemodynamic profiles ...obtained in the Framingham Heart Study and the Age, Gene/Environment Susceptibility-Reykjavik Study.
Once thought to be a consequence of longstanding hypertension, recent evidence suggests that aortic stiffness antedates and contributes to the pathogenesis of hypertension and target organ damage in the heart, brain, and kidneys. Carotid-femoral pulse-wave velocity (CFPWV) has emerged as the reference standard measure of aortic stiffness and a powerful predictor of cardiovascular disease risk. Augmentation index, a putative measure of arterial stiffness and wave reflection, has complex relations with stiffness and risk. Recent evidence suggests that wave reflection, which is a normal consequence of impedance mismatch between compliant aorta and stiff muscular arteries, is protective and limits the exposure of target organs to potentially harmful pulsatile energy. Aortic stiffening produces impedance matching that reduces wave reflection and exposes the microcirculation to excessive pulsatile stress, resulting in microvascular target organ damage and dysfunction.
CFPWV provides a powerful new tool for risk stratification and elucidation of the pathogenesis of target organ damage in hypertension.
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