Interrelations Between Arterial Stiffness, Target Organ Damage, and Cardiovascular Disease Outcomes

Abstract

Background Excess transmission of pressure pulsatility caused by increased arterial stiffness may incur microcirculatory damage in end organs (target organ damage [TOD] ) and, in turn, elevate risk for cardiovascular disease ( CVD ) events. Methods and Results We related arterial stiffness measures (carotid-femoral pulse wave velocity, mean arterial pressure, central pulse pressure) to the prevalence and incidence of TOD (defined as albuminuria and/or echocardiographic left ventricular hypertrophy) in up to 6203 Framingham Study participants (mean age 50±15 years, 54% women). We then related presence of TOD to incident CVD in multivariable Cox regression models without and with adjustment for arterial stiffness measures. Cross-sectionally, greater arterial stiffness was associated with a higher prevalence of TOD (adjusted odds ratios ranging from 1.23 to 1.54 per SD increment in arterial stiffness measure, P<0.01). Prospectively, increased carotid-femoral pulse wave velocity was associated with incident albuminuria (odds ratio per SD 1.28, 95% CI, 1.02-1.61; P<0.05), whereas higher mean arterial pressure and central pulse pressure were associated with incident left ventricular hypertrophy (odds ratio per SD 1.37 and 1.45, respectively; P<0.01). On follow-up, 297 of 5803 participants experienced a first CVD event. Presence of TOD was associated with a 33% greater hazard of incident CVD (95% CI , 0-77%; P<0.05), which was attenuated upon adjustment for baseline arterial stiffness measures by 5-21%. Conclusions Elevated arterial stiffness is associated with presence of TOD and may partially mediate the relations of TOD with incident CVD . Our observations in a large community-based sample suggest that mitigating arterial stiffness may lower the burden of TOD and, in turn, clinical CVD .

Keywords: arterial stiffness; cardiovascular disease; epidemiology; pulse wave velocity; target organ damage.

Figure 1

Conceptual framework for analyses. “a” refers to multivariable‐adjusted regression coefficient relating arterial stiffness measure to presence vs absence of target organ damage (TOD); it is the direct effect of arterial stiffness on TOD. “b” refers to multivariable‐adjusted regression coefficient relating TOD to the incidence of cardiovascular disease (CVD) (without arterial stiffness measures in the model); it is the overall effect of TOD on CVD corrected for confounders. “b’” refers to multivariable‐adjusted regression coefficient relating TOD to the incidence of CVD with additional adjustment for arterial stiffness measures; it is the direct effect of TOD on CVD incidence. “c” refers to multivariable‐adjusted regression coefficient relating arterial stiffness measures to the incidence of CVD; it is the overall effect of arterial stiffness on CVD incidence. “c’” refers to multivariable‐adjusted regression coefficient relating arterial stiffness measures to the incidence of CVD with additional adjustment for presence of TOD at baseline; it is the direct effect of arterial stiffness on CVD incidence.

Figure 2

Derivation of study samples. CVD indicates cardiovascular disease; LVH, left ventricular hypertrophy; MAP, mean arterial pressure; MRI, magnetic resonance imaging; PP, pulse pressure; PWV, pulse wave velocity; WMH, white matter hyperintensity.

Figure 3

Prevalence of target organ damage (albuminuria and left ventricular hypertrophy [LVH]) according to tertile of arterial stiffness measures. P values indicate tests of trend across tertiles of arterial stiffness measure (A, central pulse pressure [CPP]; B, mean arterial pressure [MAP]; C, carotid‐femoral pulse wave velocity [CFPWV]).

Figure 4

Prevalence of target organ damage (covert brain infarcts [CBIs] and large white matter intensities [WMHs]) according to tertile of arterial stiffness measures. P values indicate tests of trend across tertiles of arterial stiffness measure. CFPWV indicates carotid‐femoral pulse wave velocity; CPP, central pulse pressure; MAP, mean arterial pressure.

Figure 5

Incidence of cardiovascular disease (CVD) according to presence vs absence of target organ damage (TOD) (top panel) and according to tertile of arterial stiffness measure (bottom 3 panels).