Arterial Stiffness and Cerebral Small Vessel Disease: The Rotterdam Scan Study

BACKGROUND AND PURPOSE Aging and vascular risk factors contribute to arterial stiffening. Increased arterial stiffness exposes the small vessels in the brain to abnormal flow pulsations and, as such, may contribute to the pathogenesis of cerebral small vessel disease. In a population-based study, we investigated the association between arterial stiffness, as measured by aortic pulse wave velocity (aPWV), and small vessel disease. METHODS Overall, 1460 participants (mean age, 58.2 years) underwent aPWV measurement and brain MRI scanning. We calculated aPWV by measuring time differences and distances between pulse waves in the carotid and femoral arteries. Using automated MRI analysis, we obtained white matter lesion volumes. Infarcts and microbleeds were rated visually. We used linear and logistic regression models to associate aPWV with small vessel disease, adjusting for age, sex, mean arterial pressure, and heart rate and additionally for cardiovascular risk factors. Subsequently, we explored associations in strata of hypertension. RESULTS In the study group, higher aPWV was associated with larger white matter lesion volume (difference in volume per SD increase in aPWV 0.07; 95% CI, 0.02-0.12) but not with lacunar infarcts or microbleeds. In persons with uncontrolled hypertension, higher aPWV was significantly associated with larger white matter lesion volume (difference in volume per SD increase in aPWV 0.09; 95% CI, 0.00-0.18), deep or infratentorial microbleeds (OR, 2.13; 95% CI, 1.16-3.91), and to a lesser extent also with lacunar infarcts (OR, 1.63; 95% CI, 0.98-2.70). No such associations were present in persons with controlled hypertension or without hypertension. CONCLUSIONS In our study, increased arterial stiffness is associated with a larger volume of white matter lesions.

[1]  H. Struijker‐Boudier,et al.  Expert consensus document on arterial stiffness: methodological issues and clinical applications. , 2006, European heart journal.

[2]  Hae-Young Lee,et al.  Aging and arterial stiffness. , 2010, Circulation journal : official journal of the Japanese Circulation Society.

[3]  D. Duprez Is Vascular Stiffness a Target for Therapy? , 2010, Cardiovascular Drugs and Therapy.

[4]  K. Asayama,et al.  Association of Arterial Stiffness with Silent Cerebrovascular Lesions: The Ohasama Study , 2011, Cerebrovascular Diseases.

[5]  A. Hofman,et al.  Prevalence and Risk Factors of Silent Brain Infarcts in the Population-Based Rotterdam Scan Study , 2002, Stroke.

[6]  M. van Buchem,et al.  Aortic stiffness is associated with cardiac function and cerebral small vessel disease in patients with type 1 diabetes mellitus: assessment by magnetic resonance imaging , 2009, European Radiology.

[7]  A. Hofman,et al.  Incidental findings on brain MRI in the general population. , 2007, The New England journal of medicine.

[8]  A Hofman,et al.  Hypertension and cerebral white matter lesions in a prospective cohort study. , 2002, Brain : a journal of neurology.

[9]  J. Cohn,et al.  Relationship between periventricular or deep white matter lesions and arterial elasticity indices in very old people. , 2001, Age and ageing.

[10]  Yoshihiko Maehara,et al.  Association between Arterial Stiffness and Cerebral White Matter Lesions in Community-Dwelling Elderly Subjects , 2008, Hypertension Research.

[11]  E. Lakatta,et al.  Elevated Aortic Pulse Wave Velocity, a Marker of Arterial Stiffness, Predicts Cardiovascular Events in Well-Functioning Older Adults , 2005, Circulation.

[12]  Athanase Benetos,et al.  Influence of age, risk factors, and cardiovascular and renal disease on arterial stiffness: clinical applications. , 2002, American journal of hypertension.

[13]  Kun-Woo Park,et al.  Cerebral Microbleeds Are Independently Associated with Arterial Stiffness in Stroke Patients , 2008, Cerebrovascular Diseases.

[14]  Aad van der Lugt,et al.  Prevalence and Risk Factors of Cerebral Microbleeds: An Update of the Rotterdam Scan Study , 2010, Stroke.

[15]  Steven Warach,et al.  Cerebral Microbleeds : A Field Guide to their Detection and Interpretation , 2012 .

[16]  Chien-Cheng Chang,et al.  Metabolic risks, white matter hyperintensities, and arterial stiffness in high-functioning healthy adults. , 2010, International journal of cardiology.

[17]  D. Calvet,et al.  Carotid and Aortic Stiffness: Determinants of Discrepancies , 2006, Hypertension.

[18]  K. Kohara,et al.  Silent cerebral microbleeds associated with arterial stiffness in an apparently healthy subject , 2009, Hypertension Research.

[19]  Michael F O'Rourke,et al.  Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. , 2005, Hypertension.

[20]  Peter W de Leeuw,et al.  Increased Aortic Pulse Wave Velocity Is Associated With Silent Cerebral Small-Vessel Disease in Hypertensive Patients , 2008, Hypertension.

[21]  Wiro J. Niessen,et al.  White matter lesion extension to automatic brain tissue segmentation on MRI , 2009, NeuroImage.

[22]  Albert Hofman,et al.  Arterial Stiffness and Risk of Coronary Heart Disease and Stroke: The Rotterdam Study , 2006, Circulation.

[23]  J. Whitworth,et al.  2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension , 2003, Journal of hypertension.

[24]  A. Lee,et al.  Increased brachial–ankle pulse wave velocity is independently associated with risk of cerebral ischemic small vessel disease in elderly hypertensive patients , 2008, Clinical Neurology and Neurosurgery.

[25]  M. Matsumoto,et al.  Associations of Brachial-Ankle Pulse Wave Velocity and Carotid Atherosclerotic Lesions with Silent Cerebral Lesions , 2007, Hypertension Research.

[26]  M. Arfan Ikram,et al.  The Rotterdam Study: 2012 objectives and design update , 2011, European journal of epidemiology.

[27]  T. LeCompte,et al.  Vascular Structure and Function Is Correlated to Cognitive Performance and White Matter Hyperintensities in Older Hypertensive Patients With Subjective Memory Complaints , 2009, Stroke.

[28]  Yasmin,et al.  Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: ‘establishing normal and reference values’ , 2010, European heart journal.