G R O U P 9 – B E C K , B O E S C H , G A R V E R , L A D D , O U T E R B R I D G E , W H I T E

CARDIOVASCULAR DISEASE

E F F E C T S O F V I TA M I N D & Z I N C

INTRODUCTION

• Cardiovascular disease (CVD) is the leading cause of death in the United States.• Approximately 82 million people suffer some form of

CVD. • Causing about 2,200 deaths a day, averaging one death

every 39 seconds.(http://www.hopkinsmedicine.org/healthlibrary/conditions/cardiovascular_diseases/

cardiovascular_disease_statistics_85,P00243)

CARDIOVASCULAR DISEASE (CVD)

• Class of diseases that involve the heart or blood vessels (arteries, capillaries and veins).

• Types:• Coronary heart disease • Cardiomyopathy • Hypertensive heart disease • Heart Failure• Cor pulmonale • Cardiac dysrhythmias • Inflammatory heart disease• Valvular heart disease• Cerebrovascular disease• Peripheral arterial disease • Congenital heart disease • Rheumatic heart disease

RISK FACTORS

• Hypertension

• Diabetes Mellitus

• Atherosclerosis

PREVENTION

1. Avoid smoking & the use of tobacco products2. Physical Activity3. Eat a heart-healthy diet4. Maintain Healthy Weight5. Get regular health screenings

RISING QUESTIONS

Can low concentrations of 25-dihydroxyvitamin D lead to CVD?

Can low serum zinc levels lead to CVD in patients with type 2 diabetes?

VITAMIN D INTRODUCTION

“Vitamin D Deficiency and Risk of Cardiovascular Disease”

• Vitamin D receptors have broad tissue distribution that includes:• Vascular smooth muscle• Endothelium• Cardiomyoctes.

• Research for the correlation of CVD and Vitamin D deficiency from longitudinal studies are lacking which lead to the development of this study of serum vitamin D.

VITAMIN D DEFICIENCY

• Vit D deficiency highly prevalent in United States & worldwide

• Principal causes of deficiency (of 25-OH D):• Inadequate sun exposure• Pigmented skin• Inadequate dietary intake

OBJECTIVE

Low serum levels of Vitamin D is in connection to Cardiovascular disease.

VITAMIN D MATERIALS

• Framingham Heart Study (1971) • 1739 participants• Average 59 years old• No history of cardiovascular disease • All participants were white

METHODS

• Physician-administered medical history, examination, and lab assessment of vascular risk factors.

• Vitamin D intake- food questionnaire • Medical records obtained during follow-up were

evaluated related to CVD • Serum samples obtained morning after overnight

fast and frozen

RESULTS

• 28% of subjects has 25-OH D levels <15ng/mL, 9% has levels <10ng/mL.

• Follow up period (mean 5.4 years): 120 subjects had a first cardiovascular event.

• Subjects with 25-OH D levels <15ng/mL had a hazard ratio of 1.62 compared to those subjects whose 25-OH D levels were >15ng/mL.• Indicating the subject was more likely to suffer a

cardiovascular event if Vitamin D deficient.

MECHANISMS

1. 1,25 –OH D participates in the regulation of renin-angiotensin system by directly suppressing renin gene expression.

MECHANISMS

2. Vascular smooth muscle and endothelial cells express Vitamin D receptor that can cause smooth muscle proliferation, inflammation and thrombosis when vitamin D deficient. • All of which contribute to atherosclerosis.

MECHANISMS

3. Vitamin D Deficiency can cause secondary hyperparathyroidism.

High Parathyroid hormone can promote cardiac hypertrophy (left ventricular hypertrophy) and vascular remodeling due to low plasma calcium levels.

LVH develops due to high systemic systolic blood pressure and from left ventricle wall thickening and loss of elasticity which results in less than sufficient blood pumped to peripheral tissues.

ZINC INTRODUCTION

“Serum Zinc Level and Coronary Heart Disease Events in Patients With Type 2

Diabetes”

• In non-diabetic subjects there are studies suggesting that low serum level of zinc is associated with increased incidence of CVD.

• Therefore, this lead to the study of type 2 diabetic subjects.

ZINC DEFICIENCY

• Insufficient availability in diet • Malabsorption of Zinc in body. • Diseases that require body to use excessive zinc

OBJECTIVE

Investigate whether low serum zinc levels predict coronary heart disease events in

subjects with type 2 diabetes.

ZINC STUDY

Baseline Study

• 1,059 Type 2 Diabetic Patients (1982-1984)• 328 men and 221

women from West Finland

• 253 men and 257 women from East Finland

• Ages 45-64 years• 8 years average diabetic

Follow-Up Study

• 1,050 Type 2 Diabetic Patients• 326 men and 218

women from West Finland

• 250 men and 256 women from East Finland

• 7 year follow up period

METHODS

Baseline

• Conducted interviews• Chest pain symptoms for

angina pectoris recorded• All medical records were

recorded and reviewed • All blood samples drawn

at 8:00 a.m. after 12-hr fast.

• Zinc analyzed by direct atomic absorption

Follow-Up

• 1990- questionnaire about hospitalization

• Medical records of those who died between baseline experiment and December 31 1989 and those who reported chest pain

• Hospital records and autopsy reports were used

RESULTS

• A 7 Year follow up was conducted:

254 patients had a fatal or nonfatal Myocardial infarction &

156 died from coronary heart disease

CHD event rates (unadjusted) in type 2 diabetic patients according to their baseline fasting serum zinc levels divided in quartiles. ▪, CHD death (P = 0.015); ▒, nonfatal or fatal MI (P =

0.014).

Soinio M et al. Dia Care 2007;30:523-528

Copyright © 2011 American Diabetes Association, Inc.

ZINC ROLES

• Antioxidant roles

• Catalytic role: Carbonic anhydrase (CO2+H2O

H2CO3 H++HCO3)

• Superoxide dismutase (SOD) (2O-2-

+2H+H2O2+O2)

• Insulin role• Function of insulin-modulates insulin action and

improves hepatic binding of insulin

Zn ✕

ANTIOXIDANT ROLE

CONCLUSION

Vitamin D deficiency and low serum zinc levels correlate with cardiovascular disease events.

Zinc & Vitamin D

SUMMARY

VITAMIN DStrengths Weaknesses

Use of large, ambulatory cohort. No PTH levels assessed.

Longitudinal study design & long-term follow-up.

Residual cofounding – unmeasured Vitamin D deficiency characteristics.

Standardized adjudication of CVD events.

Limited variation in race population.

Use of multivariable analyses to account for comorbid conditions.

ZINCStrengths Weaknesses

Use of large cohort of type 2 diabetic patients.

Study was performed before the statin era.

Performed a 7-year follow-up for greater accuracy.

Unmeasured effect of insulin treatment with added zinc.

Adjustment for multiple factors using a cox regression analysis.

FUTURE STUDIES

• Vitamin D and its role in CVD prevention.

• Use of Zinc supplementation as an intervention for CVD to prevent atherosclerotic complications.

• Could low serum Zinc lead to CVD in the statin era.

• Use of a gold standard random clinical trial (RCT) design to help solve causative questions.

REFERENCES

• Soinio, Minna, and Jukka Marniemi. Et al. "Diabetes Care." Serum Zinc Level and Coronary Heart Disease Events in Patients With Type 2 Diabetes. Turku University Central Hospital Research Fund, Mar. 2003. Web. 16 Apr. 2013.

• Wang, Thomas J., and Michael J. Pencina. Et al. "Vitamin D Deficiency and Risk of Cardiovascular Disease." Vitamin D Deficiency and Risk of Cardiovascular Disease. American Heart Association, 7 Jan. 2008. Web. 16 Apr. 2013.

• Wathsala, Medawala. "Special Issue." A Molecular Level Understanding of Zinc Activation of C-peptide and Its Effects on Cellular Communication in the Bloodstream. SBDR, 16 Jan. 2013. Web. 18 Apr. 2013.

• Gropper, Sareen S, Smith, Jack L. Advanced Nutrition and Human Metabolism. Wadsworth Publishing. 1 June 2012.