2. Early
Vascular aging
& Arterial Stiffness

3. Features of normal vascular aging.
A gradual change of the vascular structure and function
Decreased arterial Increased arterial
compliance stiffening
Features of normal vascular aging.
Influenced by age dependent structural and biochemical changes, eg, in the
content of elastin and collagen in the vessel wall.
Subtle increased intima media thickening (IMT) in the vessel wall followed by
atherosclerosis with characteristic lesions and plaque.
Impairment of endothelial-mediated vasodilatation and decrease in fibrinolysis.
Nilsson PM1.Early vascular aging (EVA): consequences and prevention. Vasc Health Risk Manag. 2008;4(3):

4. When vascular aging takes a rapid course
Premature CVD manifestations :
Coronary heart disease (CHD),
Myocardial infarction,
Stroke
Symptoms from peripheral arterial disease (PAD).
Progressing vascular dementia :
Impaired cognitive function,
Depression
Disturbed central regulation of physiological processes, eg, blood pressure regulation.
Nilsson PM1.Early vascular aging (EVA): consequences and prevention. Vasc Health Risk Manag. 2008;4(3):

5. Features of early vascular ageing (EVA)
Increased arterial stiffness and pulse wave velocity
Impaired endothelial function and vasodilatation
Chronic vascular inflammation
Intima media thickness and early atherosclerosis
Hemorheological disturbances of blood flow
Capillary rarefaction and dysfunctional regulation
Shorter telomere length/lower telomerase activity
Impaired glucose and lipid metabolis
Insulin resistance
Oxidative stress
Arterial calcification
Increased deposition of matrix substances
Small vessel degeneration in brain and kidney
Increased left ventricular heart (LVH) load with hypertrophy
Nilsson PM1.Early vascular aging (EVA): consequences and prevention. Vasc Health Risk Manag. 2008;4(3):

6. Vascular Age Benchmark

7. Early Vascular Aging (EVA) Aging Dis. 2014 Apr; 5(2): 109–113.
Structural changes in arterial wall
Increased stiffening caused by:
A decrease in the elastin content of the arterial media
Dominance of collagen content
Increased non-enzymatic cross-linkages between collagen structures.
Nilsson PM1. Hemodynamic Aging as the Consequence of Structural Changes Associated with
Early Vascular Aging (EVA) Aging Dis Apr; 5(2): 109–113.

8. Arterial stiffness – hemodynamic effects
Changes in brachial BP
Isolated systolic hypertension (ISH)
Elevated pulse pressure (PP)
Changes in central BP
Increased central systolic BP and PP
Increased BP variability
Decreased heart rate variability
Impaired endothelial function - Less vasodilation
Impaired baroreceptor function, orthostatic hypotension
Nilsson PM1. Hemodynamic Aging as the Consequence of Structural Changes Associated with Early Vascular Aging (EVA) Aging Dis Apr; 5(2): 109–113.

9. Arterial stiffness – a nexus between cardiac and renal disease
A key driver of (chronic) human disorders
Pulmonary arterial hypertension,
Kidney disease, and
Atherosclerosis. .
Huveneers S1, Daemen MJ2, Hordijk PL2 Between Rho(k) and a Hard Place: The Relation Between Vessel Wall Stiffness,
Endothelial Contractility, and Cardiovascular Disease Circ Res Feb 27;116(5):
Jia G1, Aroor AR1, Sowers JR2Arterial Stiffness: A Nexus between Cardiac and Renal Disease. Cardiorenal Med.
2014 Apr;4(1):60-71.

10. Preventing Arterial stiffness
Role of
Vitamin D in
Preventing Arterial stiffness

11. Low serum 25-hydroxyvitamin D levels is associated with both
arterial and ventricular stiffness
Vitamin D and arterial stiffness:
Regulates the renin–angiotensin system
Suppresses proliferation of vascular smooth muscle
Improves endothelial cell dependent vasodilatation.
These mechanisms may play a role in pathogenesis of arterial and left ventricular stiffness.
Seker T1, Gür M2, Kuloğlu O2, Serum 25-hydroxyvitamin D is associated with both arterial and ventricular stiffness in healthy subjects. J Cardiol Dec;62(6):361-5.

12. Low serum 25-hydroxyvitamin D levels is associated with both
arterial and ventricular stiffness
Vitamin D deficient group have
Higher
Pulse wave velocity (PWV)
Serum calcium
Left ventricular filling index
Systolic blood pressure values
Lower
Mitral peak early/peak late flow velocities values
compared with patients with vitamin D sufficient group
Şeker T1, Gür M2, Kuloğlu O2, Serum 25-hydroxyvitamin D is associated with both arterial and ventricular stiffness in healthy subjects. J Cardiol Dec;62(6):361-5.

13. Vitamin D status and vascular effects
LVID, left ventricular inner dimension; LAD, left atrium dimension; LVMI, left ventricular mass index; PWV, pulse wave velocity.

14. Low serum 25-hydroxyvitamin D levels is associated with both
arterial and ventricular stiffness
Conclusions
Low 25-hydroxyvitamin D levels are associated with increased ventricular and arterial stiffness as well as systolic blood pressure in healthy subjects.
Arterial stiffness plays a role in pathogenesis of hypertension.
Ventricular stiffness plays a role in pathogenesis of heart failure.
Therefore, vitamin D may play a role in pathogenesis of both hypertension and heart failure.
Şeker T1, Gür M2, Kuloğlu O2, Serum 25-hydroxyvitamin D is associated with both arterial and ventricular stiffness in healthy subjects. J Cardiol Dec;62(6):361-5.

15. Vitamin D insufficiency associated with increased endothelial
dysfunction irrespective of traditional risk burden.
25-OH D levels independently associated with:
Flow-mediated vasodilation (β = 0.1, p = 0.03),
Reactive hyperemia index (β = 0.23, p < 0.001),
Pulse wave velocity (β = -0.09, p = 0.04),
Augmentation index (β = -0.11, p = 0.03),
Subendocardial viability ratio (β = 0.18, p = 0.001).
Al Mheid I1, Patel R, Murrow J, Vitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humans. J Am Coll Cardiol Jul 5;58(2):

16. Vitamin D insufficiency associated with increased
endothelial dysfunction irrespective of traditional risk burden.
Normalization of 25-OH D at 6 months was associated with :
Increase in reactive hyperemia index (0.38 ± 0.14, p = 0.009)
Subendocardial viability ratio (7.7 ± 3.1, p = 0.04),
Decrease in mean arterial pressure (4.6 ± 2.3 mm Hg, p = 0.02).
Al Mheid I1, Patel R, Murrow J, Vitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humans. J Am Coll Cardiol Jul 5;58(2):

17. Vitamin D insufficiency associated with increased
endothelial dysfunction irrespective of traditional risk burden.
Conclusions
Vitamin D insufficiency associated with :
Increased arterial stiffness and endothelial dysfunction in the conductance and resistance blood vessels in humans, irrespective of traditional risk factor burden.
Normalization of vitamin D status in insufficient individuals is associated with improvements in several parameters of vascular function
Al Mheid I1, Patel R, Murrow J, Vitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humans. J Am Coll Cardiol Jul 5;58(2):

18. Arterial stiffness, Vitamin D, CVD and CKD
Abnormalities in mineral metabolism
[calcium, phosphate, and immunoreactive parathyroid hormone (PTH)]
and vitamin D have been linked to increase in central arterial stiffness.
There is a significant association between augmentation index -
AIx (a composite measure of central arterial stiffness) and 1,25-(OH)2D3 in a diverse group of individuals with CVD, CKD, or both.
Andrade J1, Er L, Ignaszewski A, Levin AExploration of association of 1,25-(OH)2D3 with augmentation index, a composite measure of arterial stiffness. Clin J Am Soc Nephrol Nov;3(6):

19. Vitamin D, Arterial stiffness and Diabetes
Type 2 diabetes mellitus (DM) is an established major independent risk factor for cardiovascular disease.
Serum 25-hydroxyvitamin D (vitamin D) is a prevalent condition in patients with type 2
Macrovascular complications of DM are associated with stiffening of the aorta, which is a major contributing factor to the target organ damage .
Kuloğlu O1, Gür M, Şeker T Serum 25-hydroxyvitamin D level is associated with aortic distensibility and left ventricle hypertrophy in newly diagnosed type 2 diabetes mellitus. Diab Vasc Dis Res Nov;10(6):546-9. ,

20. Short Term Vitamin D Supplementation on the Inflammatory
and Oxidative Mediators of Arterial Stiffness
Authors conclude :
Vitamin D has been postulated to mediate its cardiovascular effect by
modulating the mediators of inflammation and oxidative stress
Cardiovascular benefit of vitamin D :
•May require near maximum serum 25(OH)D levels of vitamin D sufficiency
•May be more apparent in a subset of the population with an excess burden of
oxidative stress
Martins D1, Meng YX2, Tareen N1The Effect of Short Term Vitamin D Supplementation on the Inflammatory and
Oxidative Mediators of Arterial Stiffness. Health (Irvine Calif) Jun;6(12):

21. Vitamin D, Arterial stiffness and Diabetes
Patients with vitamin D deficiency group have :
Higher Left ventricle mass index (LVMI )and
Lower aortic distensibility (AD ) values
Compared with patients with vitamin D sufficient group
Kuloğlu O1, Gür M, Şeker T Serum 25-hydroxyvitamin D level is associated with aortic distensibility and left ventricle hypertrophy in newly diagnosed type 2 diabetes mellitus. Diab Vasc Dis Res Nov;10(6):546-9.

22. Vitamin D
Supplementation

23. Short Term Vitamin D Supplementation on the Inflammatory
and Oxidative Mediators of Arterial Stiffness
Monthly dose of 100,000IU of vitamin D3 for three months
Significant increase in the serum 25(OH)D levels to a mean level of 34.5 ng/ml (SD = 7.1) (p < 0.001).
The increase in 25(OH)D levels was associated with
a significant decrease in the serum level of intact PTH (p = 0.02),
mean urinary isoprostane (p = 0.02) and
adipocyte cytokine expression.
significant decrease in the augmentation index among the participants with the highest tertile of urinary isoprostane (p = 0.007).
Martins D1, Meng YX2, Tareen N1The Effect of Short Term Vitamin D Supplementation on the Inflammatory and
Oxidative Mediators of Arterial Stiffness. Health (Irvine Calif) Jun;6(12):

24. Short Term Vitamin D Supplementation on the Inflammatory
and Oxidative Mediators of Arterial Stiffness
Authors conclude :
Vitamin D has been postulated to mediate its cardiovascular effect by modulating the mediators of inflammation and oxidative stress
Cardiovascular benefit of vitamin D :
May require near maximum serum 25(OH)D levels of vitamin D sufficiency
May be more apparent in a subset of the population with an excess burden of oxidative stress
Martins D1, Meng YX2, Tareen N1The Effect of Short Term Vitamin D Supplementation on the Inflammatory and
Oxidative Mediators of Arterial Stiffness. Health (Irvine Calif) Jun;6(12):

25. Summary Arterial stiffness is a feature of early vascular aging
Low vitamin D levels are associated with both arterial and ventricular stiffness
Vitamin D plays a major role in pathogenesis of heart failure and hypertension
Supplementation of Vitamin D modulates cardiovascular inflammatory mediators and oxidative stress.