This document summarizes two studies on the relationship between vitamin D/zinc deficiency and cardiovascular disease. The first study found that subjects in the Framingham Heart Study with vitamin D levels below 15 ng/mL were 62% more likely to experience a cardiovascular event over 5 years than those with higher levels. Low vitamin D may increase heart disease risk by impacting the renin-angiotensin system and promoting inflammation. The second study observed type 2 diabetic patients in Finland over 7 years, finding that those with lower serum zinc levels had higher rates of heart attacks and coronary heart disease deaths. Low zinc may raise heart disease risk by reducing antioxidant defenses. Future research is still needed to better understand these relationships and potential benefits of supplementation
2. 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_statisti
cs_85,P00243)
5. PREVENTION
1.
2.
3.
4.
5.
Avoid smoking & the use of tobacco products
Physical Activity
Eat a heart-healthy diet
Maintain Healthy Weight
Get regular health screenings
6. 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?
7. 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.
8. 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
10. VITAMIN D MATERIALS
•
•
•
•
•
Framingham Heart Study (1971)
1739 participants
Average 59 years old
No history of cardiovascular disease
All participants were white
11. 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
12. 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.
13.
14. MECHANISMS
1. 1,25 –OH D
participates in
the regulation
of reninangiotensin
system by
directly
suppressing
renin gene
expression.
15. 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.
16. 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.
17. 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.
20. 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
21. 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
22. RESULTS
• A 7 Year follow up was conducted:
254 patients had a fatal or nonfatal
Myocardial infarction &
156 died from coronary heart disease
29. VITAMIN D
Strengths
Weaknesses
Use of large, ambulatory cohort.
No PTH levels assessed.
Longitudinal study design & longterm 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.
Strengths
ZINC
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.
30. 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.
31. 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.
Hinweis der Redaktion
Background and introduction for vit D and zinc
Modulation of these risk factors due to a deficiency in Vitamin D or Zinc lead to CVD.
Use book, ling’s slidesFunctions:Increases serum calciumMaintains phosphorus homeostasisInvolved in muscle functionHelps regulate blood pressure
Participants were From the Framingham Offspring cohort conducted originally in 1971. between 1996 and 2001, 1,972 of the participants had their 25-OH D levels measured. Of this 233 were not eligible because of prior CV disease or kidney disease. So there was a total of 1,739 remained eligible. Average of 59 years old and no history of cardiovascular disease. Also, because of the historical framework of the original framingham study all participants were white.
Hypertension, current smoking status, physical activity, and diabetes Detailed food questionnaires asking about vitamin D intake from dietary sources of supplements. Follow up---Medical records were obtained for hospitalizations and physician visits related to CV disease. CVD include- myocardial infarction, coronary insufficiency, angina, stroke, transient ischemic attack, peripheral claudication, or heart failure. Frozen no more than 3 years.
Hazard ratio is a comparison statistic. 1.00 is a baseline comparison #. ,
There was also a marked increase in cardiovascular risks in multivariable adjusted hazard ratios for subjects whose 25-OH D levels were between 10 to <15ng/mL and those whose levels were <10ng/mL. Hazard ratios where 1.53 and 1.80 respectively.
Vitamin D deficiency (<15ng/mL) leads to an increase in renin expression which increases reninangiotensin 2 which contributes to hypertension. Angiotensin II is a potent vaso-constrictor causing a rise in systolic blood pressure.
Functions:Component of many metalloenzymesRegulates gene transcriptionZn fingers
Signs:Compromised immune systemDiarrhea Loss of appetiteImpairment of cognitive and motor functionsHair loss and skin lesions Sight and smell and negative effect on ability to remember things
Baseline study 1982-1984. Ages 45-64 8 yrs. Average diabetic. Type 1 Diabetes was excluded Zinc, Mean Age, duration of diabetes, total cholesterol, HDL cholesterol, triglycerides, HbA1, BMI, current smokers, and hypertension
Interviews---history of smoking, alcohol intake, physical activity, use of medication, and history of chest pain suggestive of CHDAngina pectoris- angina – is chest pain due to ischemia of the heart muscle, generally due to obstruction or spasm of the coronary arteries.Blood sample- glucose levels, serum lipid and lipoprotein levels, triglyceride levels. ZINC was analyzed by direct atomic absorption spectrophotometry about 10 yrs. After baseline study from stored samples. Questionnaire sent to every surviving participant of the original study (for acute chest pain)
The mean serum zinc level was statistically significantly lower in men and women who died from CHD than in those who did not (P = 0.016 and P = 0.022, respectively)The mean unadjusted serum zinc level was also lower in those men and women who had a fatal or nonfatal MI than in those who did not (P = 0.022 and P = 0.004, respectively).
Zinc is a coenzyme for two different reactions that help convert harmful species into unharmful molecules. Without the presence of zinc these reactive species could oxidize LDL in the body which is a key component of the formation of atherosclerosis. One of these enzymes carbonic anhydrase catalyzes the reaction of carbonic acid to an un-harmful hydrogen atom and bicarbonate.The other reaction involves the enzyme superoxide dismutase which catalyzes the reaction of 2 reactive oxygen species to hydrogen peroxide and oxygen.
This picture from Nutrition 314 helps depict the negative effects of oxidized LDL. As you can see in this picture LDL is transported inside the cell from the blood and can potentially be oxidized. It is then transported into a macrophage and stored near the endothelial cell layer. The accumulation of these macrophages will cause the formation of foam cells which is the key process in the formation of atherosclerosis. When the body has a sufficient amount of zinc in the body it can inhibit the oxidation of LDL which would in theory help prevent atherosclerosis.
This picture here is of a pancreatic beta cell. The B-cells contain granular’s where the insulin is produced. These granulars also have zinc transporters in the form of ZnT-8 shown here and ZnT-5. As insulin is produced zinc is stored with the insulin until it is released. A zinc deficiency decreases the insulin response, resulting in impaired glucose tolerance which increases the risk for type 2 diabetes. Type 2 diabetes is a major risk factor for cardiovascular disease as explained previously. There have also been previous studies conducted that have shown that serum zinc levels are lower in diabetic patients than in non diabetic patients which is thought to be caused by a higher zinc urinary excretion. Victoria is going to conclude the presentation
Vitamin D deficiency Renin-angiotension systemSmooth muscle proliferationSecondary hyperparathyroidismLow serum zinc level Antioxidant functionModulation of insulin action
Zn supplementation in RCT to tell a causative effect and correlation of zinc intake with risk of death and myocardial infraction.
