VITAMIN D DEFICIENCY&

CARDIOVASCULAR RISKS

HYPE OR REALITY

Dr. Dibbendhu KhanraDr. A. Talukdar

Medical College, Kolkata

OBJECTIVE

Introduction Vit D: Metabolism & MOA Cardiovascular risks & mortality Deficiency status/ Treatment

recommendation Our experience and Conclusion

A PubMed search with “vitamin D” and selecting articles published in the past two years resulted in more than 2,864 hits

Vitamin D

The Nobel prize for chemistry for 1928 was awarded to Adolf Windaus, the first person to receive an award mentioning ‘vitamins’. What was the contribution Windaus made to our knowledge of vitamins that deserved the highest scientific accolade?

(New York Times 1978)

Superstar

Heart,, DMCancer, Obesity, RA, TB, Depression..etc

“SUNSHINEVITAMIN”

SECOND MASSENGER

BIOCHEMISTRY

MOLECULAR BIOLOGY

VIT D RECEPTOR

Also- Brain- Beta cells- Adipose tissue

Status of Vit D hyped over time

Li et al, Tomaschitz et al, Forman et al

Apoptosis Fibrosis Vascular SMC hypertrophy

calcium effect on insulin secretionexpression of the insulin receptor

enhancing insulin responsiveness for glucose transport

hsCRP, IL10MMP9

UVB radiation from tanning 3 times a week for 3 months led to a nearly 200% increase in

25(OH)D levels and a 6 mmHg decrease in both systolic and diastolic blood pressure Krause R. Lancet 1998

Vit D deficiency & hypertension

In the NHANES III study, the average SBP was nearly 3 mm Hg lower in subjects with

the highest quartile of 25(OH)D compared to subjects in the lowest quartile Scragg R. Third National Health and Nutrition Examination Survey. Am J Hypertens 2007

Vit D deficiency & DM

A study of >10,000 Finnish children who were given 2,000 IU vitamin D3 per day

during the first year of life demonstrated a 78% reduced risk of type 1 diabetes over a 30-

year follow-up. Subsequently, this finding was confirmed by a meta-analysis of 5

observational studies in England. Hyppönen E, Lancet 2001, Zipitis CS Arch Dis Child 2008

Daily intake of >800 IU of vitamin D compared with <400 IU vitamin D reduced the risk

of T2DM by nearly one-third. It is hoped that starting vitamin D supplementation soon after

birth may be a protective strategy against the development of type 1 diabetes. Pittas AG. Diabetes Care 2006, Rifkin J. Pract Diabetol 2009

Low vitamin D levels have also been shown to be predictive of the future development

of type 2 diabetes. Increasing vitamin D serum levels to normal led to a 55% relative

reduction in the risk of developing type 2 diabetes. Forouohi NG. Diabetes 2008, Parker J. Maturitas 2010

In high-risk type 2 diabetic patients with elevated UAER, low levels of vitamin D are

associated with asymptomatic CAD. Joergensen . Diabetes Care 2011

Administration of 1,25(OH)2Din the setting of vitamin D deficiency has been shown to

down-regulate inflammatory biomarkers such as CRP.

Schleithoff SS. Am J Clin Nutr 2006

In a 10-year follow-up of 18,225 men in the Health Professionals Follow-up Study,

low levels of 25(OH)D were associated with higher risk of myocardial infarction, even

after controlling for other CHD risk factors.

Giovannucci E. Arch Intern Med 2008

In an analysis of 27,000 patients from the Inter-mountain Healthcare System, the

prevalence of vitamin D deficiency (<30 ng/ml) was 60%; and vitamin D deficiency was

associated with highly significant (p <0.0001) increases in the prevalence of dyslipidemia. Anderson JL. Am J Cardiol 2010

A recently published multicenter study evaluating patients admitted with acute coronary

syndromes found that 96% of these patients had abnormal 25(OH)D levels<30 ng/ml.

Lee JH. Am J Cardiol 2011

Vit D deficiency & ACS/IHD

Vit D deficiency & depression

vitamin D concentrations have been found to be low in patients with mood disorders,

including depression. Kalueff A. CNS Neurol Disord Drug Targets 2006

In data from the NHANES III study, in nearly 8,000 noninstitutionalized U.S. residents,

the likelihood of having depression was significantly higher among those with vitamin D

deficiency. Ganji V. Int Arch Med 2010

Vit D deficiency & Hemodialysis

Vit D deficiency & mortality

After stardom comes controversy!

Vit D deficiency & controversies

Prospective trials of vitamin D and diabetes to date were either too small or used

inadequate amounts of vitamin D. Schwallenberg G Can Fam Phys

2008 Another meta-analysis of 8 randomized trials showed statistically nonsignificant reduction

in CV disease risk with vitamin D supplementation at moderate to high doses

(approximately 1,000 IU daily) Wang L. Ann Intern Med 2010

A very recent meta-analysis of 51 studies found that the effects of vitamin D were

nonsignificant on the endpoints of death, myocardial infarction, and stroke. Elamin MB. Am J Cardiol 2011

In a meta-analysis of 10 trials, supplementation with vitamin D only nonsignificantly

reduced systolic blood pressure by 2 mm Hg and did not reduce diastolic blood pressure DerSimonian R. Control Clin Trials 2012

Will the hype regarding thisvitamin/hormone will stand the test of time?

Will this ‘jack of all trade’ vitamin D pass the rigors of randomized controlled trials?

Will vitamin D be another vitamin E, C, or folic acid, or will the results be more similar to those with omega-3

fatty acids (or better)?

VITAMIN D: HYPE OR REALITY

New challenge is on the way for vitamin D

SELECTED FOOD SOURCES OF VIT D

Food IU/serving

Cod Liver Oil, (1 tablespoon) 1,360

Wild Salmon, (3 oz) 600-1,000

Farmed Salmon, (3 oz) 100-250

Mackerel, (3 oz) 345

Tuna fish in oil, (3 oz) 200

Sardines in oil, (1 oz) 250

Milk, (1 cup) 98

NIH

TREATMENT RECOMMENDATIONS FORVITAMIN D DEFICIENCY

Vitamin D Deficiency25(OH)D < 20 ng/dL

60,000 IU of D2 or D3 Per Week X 8 weeks

Maintenance Therapy

60,000 IU of D2 Every month

Recheck 25(OH)D in 3 to 6 months

Statin myopathy Metformin induced peripheral neuropathy

SPECIFIC OBJECTIVES OF THE STUDY

1. To assess serum 25-Hydroxy vitamin D levels in Ischemic heart disease

patients and their age, sex matched controls

2. To compare the vitamin D status between Ischemic heart disease cases and the

control group and see if there is any relationship between vitamin D deficiency and

Ischemic heart disease

3. To explore for any correlation between vitamin D levels and other

conventional cardiovascular risk factors in Ischemic heart disease

A STUDY OF VITAMIN D LEVELS IN PATIENTS OF ISCHEMIC HEART DISEASE WITH SPECIAL REFERENCE TO ITS ROLE AS A

CARDIOVASCULAR RISK FACTOR

EXCLUSION CRITERIA

a) All known/diagnosed patients of DM/on OHA/

insulin therapy

b) All known/ suspected patients of osteomalacia

c) Patients suffering from neoplastic disease

d) Patients older than 70 years and younger than

30 years.

e) Patients of chronic renal failure

INCLUSION CRITERIA

nondiabetic patients between age group of

30-70 years seeking medical attention with the

complaint of acute chest pain/ chest

discomfort/ dyspnea/ orthopnea etc, together

with either elevated serum cardiac biomarkers/

Echocardiographic evidence of new onset

regional wall motion abnormality of left

ventricle/ specific ECG changes consistent with

myocardial ischemia/infarction. Along with

this symptomatic patients of chronic ischemic

heart disease with either documented TMT test

positive ECG or prior history of acute

coronary syndrome (STEMI/ NSTEMI) as

evident by ECG changes of old infarction will

be taken.

PARAMETERS

a) Serum 25(OH) vitamin D levels.

b) Serum lipid profile.

c) Fasting and postprandial blood sugar

CONCLUSION

Vit D levels correlate with CV Disease

Supplementation possibly may improve CV Outcomes but trials are needed

Vit D levels should be obtained in CV patients and supplementation considered, especially if treated with Statins

Thank you