2. Association between Hypomagnesaemia and Hyperuricemia Accompany More Severe Forms of Atherosclerosis and Inflammatory Syndrome in Patients with Cardiovascular Disease from Romania.
Ioan A. Gutiu1, Anton I. Gutiu2, Flavian S. Radulescu1, Leon Dumitrescu3
1) “Carol Davila” University of Medicine and Pharmacy, Bucharest, 2)Private Family Office-Ilfov District. Romania.3)Private Dental Office, Chiajna, Ilfov District, Romania

3. Magnesium Essential element with numberous functions in CV system:
Modulates transmembranar transport of calcium, Na, K
Regulates contractile proteins
Regulates oxidative-phosphorylation reactions
Intervenes in mithocondrial energy activities

4. Magnesium
May increase intracelular Na and Ca (by ATPase Na-K pump) . May promote vasoconstriction and increase vascular resistance.
Intervenes in activity of some enzymes such as lecithin-cholesterol acyl transferase and lipoproteinlipase.
Etc.

5. 2) Uric acid
Uric Acid (UA) is the metabolic end product of purine metabolism in humans; excess accumulation can lead to various diseases. Its possible role in CVD was firstly signaled by Davis (1897). In 1960 , the relationships between uric acid and CVD were rediscovered. There is some controversies concerning a role for uric acid in CVD (for example Framingham Heart Study) but the last studies demonstrated the link:
A relatioship between serum uric acid level and arterial hypertension
A relationship betweeun uric acid and metabolic syndrome

6. 2) Uric acid
3. High serum uric acid level promote atherosclerosis vascular disease (carotid, coronary, peripheral arteries)
4. Increased serum uric acid promote non-specific inflammation by increasing soluble intercellular adhesion molecule type I, plasminogen activator inhibitor, CRP, etc.

7. 2) Uric acid
Uric acid may increase renin level and decrease nitric oxide in renal microvascular system.
May stimulate increased of ROS
Stimulate proliferation of vascular smooth muscle cells (promote vascular remodelation)
Produce inhibition of endothelial cell growth

8. 2) Uric acid
9. In metabolic syndrome hyperuricemia association is a promoting factor for atherosclerosis (for example: uric acid is an independent factor for carotid atherosclerosis in Japanese elderly population –Takayama S. 2012)
10. Some experimental studies demonstrated a beneficial effects of hyeruricemia treatment for hypertension and for some atherosclerosis risk factors.
Conclusion: Uric acid may play an important role in atherogenesis and its consequences

9. 3) Hypothetically, association of hypomagnesiaemia and hyperuricemia may have cumulated effects in promoting of atherogenesis and cardiovascular disease

10. Methods:
In a cross-sectional observational study were analyzed 405 patients with cardiovascular disease:
angina pectoris 199(49%.),
old myocardial infarction 101(25%),
stroke 61(15%),
ischemic cardiomyopathy 28(7%),
peripheral arterial disease 16(4%).

11. Cases Mean age was 55.8+/-12.2 years, 127 (31%) were men.
Mean serum Mg level was 2.12+/-0.37mg/dl (low level first tertile <=1.9 mg/dl, high tertile >=2.19 mg/dl).
Mean serum uric acid was 4.49 mg/dl
(low level first tertile <=4.40 mg/dl , high tertile >=573 mg/dl

12. Patients grouping on serum magnesium tertiles
Serum magnesium mg/dl (Tertiles)
Tertiles 1 2 3
Serum level
mg/dl
mg/dl
>2.19 mg/dl
No patients
304
297
336

13. Patients grouping on serum uric acid tertiles
Serum uric acid-mg/dl (Tertiles)
Tertiles 1 2 3
Serum level
mg/dl
mg/dl
>5.73 mg/dl
No patients
282
278
270

14. CARDIOVASCULAR RISK FACTORS ACORDING TO MAGNESIUM AND URIC ACID TERTILES
VARIABLE
MG=1&SUA=3
MG>1&SUA<3 P
No of pts
55 (13.3%)
350
Age (years)
61.5+/-8.2
53.3+/-10.5
0.0001
Tooth loss (no)
18.4+/-8.41
15.6+/-9.4
0.0379
Cholesterol (mg/dl)
220.6+/-59.5
218.8+/-52.0
0.8150
Triglicerides (mg/dl)
228.5+/-175.8
144.5+/-108.8
Fibrinogen (mg/dl)
410.8+/-175.4
376.9+/-110.4
0.0499
S. Glucose (mg/dl)
128.9+/-52.2
95.7+/-25.7
Leucocytes
70.8+/-25.1
72.5+/-17.9
0.5376
SmokingIndex
2.15+/-9.27
2.7+/-9.6
0.6915

15. LIPIDS ASPECTS IN THE TWO TERTILES GROUPS (Mg=1&SUA=3 AND Mg>1%SUA<3)

16. INFLAMMATION IN THE STUDY GROUPS (Mg=1&SUA=3 AND Mg>1%SUA<3)

17. Other risk factors analyzed

18. Discussion
About deleterious effects of hypomagnesaemia in patients with CVD: there are a number of papers which underline exacerbation of inflammatory response, endothelial dysfunction, exacerbation of other CVD risk factors such as smoking, diabetes, hypertension.

19. Discussion
A number of studies show that treatment of hypomagnesaemia by diet supplements of magnesium may modify favorable these disorders.

20. Discussion About the effects of hyperuricemia in CVD:
we must retain: promoting of vascular atherosclerosis, relationship with arterial hypertension, exacerbating of inflammation, relationship with metabolic syndrome, endothelial dysfunction. Some studies confirm a possible favorable effect of treatment with anti-uricemic drugs.

21. Discussion
Association of hypomagnesaemia and hyperuricemia seems to have a synergistic effect in atherosclerosis promoting, especially on endothelial dysfunction, inflammation, dyslipidemia, exacerbating of other CVD risk factors.

22. Conclusions
These data offer a new point of view in diagnosis and in treatment possibilities of a special group of patients. In hypomagnesaemia some experimental and clinical studies sustain that diet supplementation with magnesium may reduce these deleterious effects. In hyperuricemia, even in cases with minimal increase of serum level, is possible a treatment by drugs (such as Allopurinol) with favorable changes.