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

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

Magnesium 5. 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.

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

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.

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

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

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

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%).

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

Patients grouping on serum magnesium tertiles Serum magnesium mg/dl (Tertiles) Tertiles 1 2 3 Serum level 0.7-1.9 mg/dl 2.0-2.19 mg/dl >2.19 mg/dl No patients 304 297 336

Patients grouping on serum uric acid tertiles Serum uric acid-mg/dl (Tertiles) Tertiles 1 2 3 Serum level 0.96-4.40 mg/dl 4.40-5.73 mg/dl >5.73 mg/dl No patients 282 278 270

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

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

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

Other risk factors analyzed

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.

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

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.

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.

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.