Early

Vascular aging

& Arterial Stiffness

Normal vascular aging

Nilsson PM1.Early vascular aging (EVA): consequences and prevention. Vasc Health Risk Manag. 2008;4(3):547-52.

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.

When vascular aging takes a rapid course

Nilsson PM1.Early vascular aging (EVA): consequences and prevention. Vasc Health Risk Manag. 2008;4(3):547-52.

Premature CVD manifestations : Coronary heart disease (CHD), Myocardial infarction, StrokeSymptoms from peripheral arterial disease (PAD).

Progressing vascular dementia :Impaired cognitive function, DepressionDisturbed central regulation of physiological processes, eg, blood pressure regulation.

Features of early vascular ageing (EVA)

Nilsson PM1.Early vascular aging (EVA): consequences and prevention. Vasc Health Risk Manag. 2008;4(3):547-52.

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

Vascular Age Benchmark

Structural changes in arterial wall

Nilsson PM1. Hemodynamic Aging as the Consequence of Structural Changes Associated with Early Vascular Aging (EVA) Aging Dis. 2014 Apr; 5(2): 109–113.

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.

Arterial stiffness – hemodynamic effects

Nilsson PM1. Hemodynamic Aging as the Consequence of Structural Changes Associated with Early Vascular Aging (EVA) Aging Dis. 2014 Apr; 5(2): 109–113.

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

Arterial stiffness – a nexus between cardiac and renal disease

.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. 2015 Feb 27;116(5):895-908.Jia G1, Aroor AR1, Sowers JR2Arterial Stiffness: A Nexus between Cardiac and Renal Disease. Cardiorenal Med.

2014 Apr;4(1):60-71.

A key driver of (chronic) human disorders

Pulmonary arterial hypertension,

Kidney disease, and

Atherosclerosis.

Role of

Vitamin D inPreventing Arterial stiffness

Low serum 25-hydroxyvitamin D levels is associated with both arterial and 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. 2013 Dec;62(6):361-5.

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.

Low serum 25-hydroxyvitamin D levels is associated with both arterial and ventricular stiffness

Şeker T1, Gür M2, Kuloğlu O2, Serum 25-hydroxyvitamin D is associated with both arterial and ventricular stiffness in healthy subjects. J Cardiol. 2013 Dec;62(6):361-5.

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 valuescompared with patients with vitamin D sufficient group

Vitamin D status and vascular effects

LVID, left ventricular inner dimension; LAD, left atrium dimension; LVMI, left ventricular mass index; PWV, pulse wave velocity.

Low serum 25-hydroxyvitamin D levels is associated with both arterial and ventricular stiffness

Şeker T1, Gür M2, Kuloğlu O2, Serum 25-hydroxyvitamin D is associated with both arterial and ventricular stiffness in healthy subjects. J Cardiol. 2013 Dec;62(6):361-5.

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.

Vitamin D insufficiency associated with increased endothelial dysfunction irrespective of traditional risk burden.

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. 2011 Jul 5;58(2):186-92.

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).

Vitamin D insufficiency associated with increased endothelial dysfunction irrespective of traditional risk burden.

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. 2011 Jul 5;58(2):186-92.

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).

Vitamin D insufficiency associated with increased endothelial dysfunction irrespective of traditional risk burden.

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. 2011 Jul 5;58(2):186-92.

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

Arterial stiffness, Vitamin D, CVD and CKD

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. 2008 Nov;3(6):1800-6.

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.

Vitamin D, Arterial stiffness and Diabetes

.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. 2013 Nov;10(6):546-9. ,

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

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). 2014 Jun;6(12):1503-1511

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. 2013 Nov;10(6):546-9.

Vitamin D

Supplementation

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). 2014 Jun;6(12):1503-1511

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). 2014 Jun;6(12):1503-1511

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.