Early Vascular aging Arterial Stiffness Normal vascular aging

Early Vascular aging & Arterial Stiffness

Normal vascular aging § A gradual change of the vascular structure and function Decreased arterial compliance Increased arterial 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 PM 1. Early vascular aging (EVA): consequences and prevention. Vasc Health Risk Manag. 2008; 4(3): 547 -52.

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 PM 1. Early vascular aging (EVA): consequences and prevention. Vasc Health Risk Manag. 2008; 4(3): 547 -52.

Features of early vascular ageing (EVA) §Increased arterial stiffness and pulse wave velocity §Impaired glucose and lipid metabolis §Insulin resistance §Impaired endothelial function and vasodilatation §Oxidative stress §Chronic vascular inflammation §Arterial calcification §Intima media thickness and early atherosclerosis §Increased deposition of matrix substances §Hemorheological disturbances of blood flow §Small vessel degeneration in brain and kidney §Capillary rarefaction and dysfunctional regulation §Increased left ventricular heart (LVH) load with hypertrophy §Shorter telomere length/lower telomerase activity Nilsson PM 1. Early vascular aging (EVA): consequences and prevention. Vasc Health Risk Manag. 2008; 4(3): 547 -52.

Vascular Age Benchmark

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 PM 1. Hemodynamic Aging as the Consequence of Structural Changes Associated with Early Vascular Aging (EVA) Aging Dis. 2014 Apr; 5(2): 109– 113.

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 PM 1. Hemodynamic Aging as the Consequence of Structural Changes Associated with Early Vascular Aging (EVA) Aging Dis. 2014 Apr; 5(2): 109– 113.

Arterial stiffness – a nexus between cardiac and renal dise §A key driver of (chronic) human disorders §Pulmonary arterial hypertension, §Kidney disease, and §Atherosclerosis. . Huveneers S 1, Daemen MJ 2, Hordijk PL 2 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 G 1, Aroor AR 1, Sowers JR 2 Arterial Stiffness: A Nexus between Cardiac and Renal Disease. Cardiorenal Med. 2014 Apr; 4(1): 60 -71.

Role of Vitamin D in Preventing Arterial stiffness

Low serum 25 -hydroxyvitamin D levels is associated with b 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 T 1, Gür M 2, Kuloğlu O 2, Serum 25 -hydroxyvitamin D is associated with both arterial and ventricular stiffness in healthy subjects. J Cardiol. 2013 Dec; 62(6): 361 -5.

Low serum 25 -hydroxyvitamin D levels is associated with b 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 T 1, Gür M 2, Kuloğlu O 2, 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 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 b 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 T 1, Gür M 2, Kuloğlu O 2, 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 insufficiency associated with increased endothe 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 I 1, 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.

Vitamin D insufficiency associated with increased endothelial dysfunction irrespective of traditional risk burd §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 I 1, 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.

Vitamin D insufficiency associated with increased endothelial dysfunction irrespective of traditional risk burd §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 I 1, 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.

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)2 D 3 in a diverse group of individuals with CVD, CKD, or both. Andrade J 1, Er L, Ignaszewski A, Levin AExploration of association of 1, 25 -(OH)2 D 3 with augmentation index, a composite measure of arterial stiffness. Clin J Am Soc Nephrol. 2008 Nov; 3(6): 1800 -6.

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 O 1, 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. ,

Short Term Vitamin D Supplementation on the Inflammator 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 D 1, Meng YX 2, Tareen N 1 The 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 O 1, 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 Inflammator and Oxidative Mediators of Arterial Stiffness Monthly dose of 100, 000 IU of vitamin D 3 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 D 1, Meng YX 2, Tareen N 1 The 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 Inflammator 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 D 1, Meng YX 2, Tareen N 1 The 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.