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CHRONICLES IN CHOLESTEROLAn Insiders Guide to State of The Art Cardiovascular

Prevention Laboratory Testing Available FromEverest Clinical Laboratories

Vitamin D circulates as a hormone, regulating theconcentration of calcium and phosphate in the bloodstreamand promoting the healthy growth and remodeling of bone.Vitamin D prevents rickets in children and osteomalacia inadults, and, together with calcium, helps to protect olderadults from osteoporosis.

Vitamin D3 is made in the skin when 7-dehydrocholesterol reacts with ultraviolet light. Vitamin D iscarried in the bloodstream to the liver, where it is convertedinto the prohormone calcidiol. Circulating calcidiol maythen be converted into calcitriol, the biologically active form

of vitamin D, either in the kidneys or by macrophages.Following the final converting step in the kidney, calcitriol

(the physiologically active form of vitamin D) is releasedinto the circulation. By binding to vitamin D-bindingprotein (VDBP), a carrier protein in the plasma, calcitriol istransported to various target organs.

Calcitriol mediates its biological effects by binding tothe nuclear vitamin D receptor which acts as a transcriptionfactor for the expression of transport proteins which areinvolved in calcium absorption in the intestine.

New evidence, that links low levels of vitamin D and higherrisk of cardiovascular disease is accumulating. Mostrecently, research has shown that serum levels of 25(OH)D less than 30 ng/mL are associated with an increased riskfor myocardial infarction (MI). Men with 25(OH)D of at least30 ng/mL had approximately half the risk of MI,independent of other cardiovascular risk factors. Anotherrecently published study looked at vitamin D levels inpatients scheduled for coronary angiographyand followed them for 7.7 years. Low Vitamin D levels wereassociated with a hazard ratio of 2.08 in comparison withthose patients with normal levels. Findings from theNational Health and Nutrition Examination Survey(NHANES) data indicate a strong association between lowvitamin D levels and peripheral artery disease (PAD) withthe incidence of PAD rising by 35% for each 10 ng/mLdecline in serum 25(OH)D levels, even after adjusting forCVD risk factors. Low Vitamin D levels are associated with

hypertension, obesity, glucose intolerance, and metabolicsyndrome.

November, 2011 VOL 1 ISSUE 2

In This Issue: Vitamin D

Cardiovascular diseaseand Vitamin D:

An Important Link

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Vitamin D may exert its effect on the risk for cardiovasculardisease via vascular smooth muscle cell proliferation,inflammation, vascular calcification or the renin-angiotension system.

VitaminD deficiency has also been linked to other chronicillnesses including autoimmune diseases, colon,prostrateand breast cancer, polycystic ovarian syndrome, multiplesclerosis and Type 1 diabetes mellitus.

In addition to increasing risk for chronic illness, low vitaminD status adversely affects muscle performance and maycontribute to perceived myalgias. Vitamin D receptors arepresent in human muscle tissue. Vitamin D mediatedeffects via alterations of intracellular calcium status are alsolikely to affect muscle function.Vitamin D deficiency hasbeen associated with proximal muscle weakness, loss ofmuscle mass, and increased risk of falling. A study showedthat 93% of persons admitted to a hospital emergency room

with muscle aches and bone pain were deficientin vitamin D.

Muscle weakness, myalgias and arthritic symptoms inpatients with vitamin D deficiency or insufficiency can posea challenge when treating patients with statins and otherlipid medications that affect muscle myocytes.

Assessment of Vitamin DThe major sources of vitamin D for humans are fromexposure to sunlight, diet, and dietary supplements. Solarultraviolet B (UVB) radiation penetrates the skin andconverts vitamin D precursors to Vitamin D3. Vitamin D

from the skin and diet is metabolized in the liver to25(OH)D. Circulating serum 25(OH)D is the best functionalmeasure of vitamin D status.

1,25 (OH) Vitamin D is necessary for the absorption ofdietary calcium. Thus, a common cause of high 1,25-dihydroxy-vitamin D is low 25(OH)D or vitamin D deficiency.Therefore, 25(OH)D is the most accurate test to assess fordeficiency.

Serum 25(OH)D concentrations vary by season and onemeasurement may not adequately reflect a persons vitaminD status over the course of a year. Vitamin D levels can beaffected by such factors assun exposure, skin

pigmentation, and age.

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By Spencer Kroll MD PhD

National Lipid Association Board Certified

Board of Directors, Northeast Lipid Association

Definition, Causes and Prevalence of Vitamin DDeficiency

A 25(OH)D serum level less that 20 ng/mL indicatesdeficiency and 2129 ng/mL is consideredinsufficiency. The optimal range of serum 25(OH)D level isstill the subject of debate but is assumed to be 3250 ng/mor higher.

It is estimated that 1 billion people worldwide have vitamindeficiency or insufficiency. Of the many causes of vitamindeficiency, reduced skin synthesis is one of the majorcontributors. Season, latitude and time of day significantlyaffect Vitamin D Synthesis. Sunscreen SPF 8 reducesVitamin D synthesis by 92.5% and SPF 15 by 99%. Darkskin pigmentation requires 36 times as much sunlightexposure to attain the same concentration of Vitamin D aslighter skin. The deficiency from photoproduction declineswith aging. Decreased bioavailability of Vitamin D occurs

obesity with sequestration of Vitamin D in body fat.Reduction of fat absorption in diseases such as cysticfibrosis, Crohns disease, and with medications that reduccholesterol absorption, bile sequestrants as well as orlistacan impair the bodys ability to absorb Vitamin D.

Anticonvulsants, glucocorticoids,cimetidine, antituberculosagents, HAART (highly active antiretroviral therapy) maylower 25(OH)D levels by either preventing vitamin Dabsorption or accelerating the catabolism through p450interactions. Thiazide diuretics and some statinshave been found to increase 25(OH)D levels. The recentreport that atorvastatin therapy for 12 monthssignificantly increased 25(OH)D levels in patients with acuischemic heart disease suggests that some of the anti-

inflammatory pleiotropic effects of statins may be mediatethrough increases in vitamin D levels.

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