Interactions of medication, physical exer and folic acid supplementation on reduct of blood pressure and/or plasma homocyst in hypertensive subjects Avany F. Pereira, Fábio L. Orsatti, Franz H. P. Bur Maria Dorotéia Borges-Santos, Roberto C. Burini* UNESP Medical School (Botucatu- SP) Brasi w w w.cem enutri.fm b.unesp.br cem enutri@ fmb.unesp.br
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Interactions of medication, physical exercise and folic acid supplementation on reductions
Interactions of medication, physical exercise and folic acid supplementation on reductions of blood pressure and/or plasma homocysteine in hypertensive subjects. Avany F. Pereira, Fábio L. Orsatti, Franz H. P. Burini, Maria Dorotéia Borges-Santos, Roberto C. Burini*. - PowerPoint PPT Presentation
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Interactions of medication, physical exerciseand folic acid supplementation on reductions
of blood pressure and/or plasma homocysteinein hypertensive subjects
Avany F. Pereira, Fábio L. Orsatti, Franz H. P. Burini, Maria Dorotéia Borges-Santos, Roberto C. Burini*
ABSTRACTHyperhomocysteine (HyHcy) and hypertensive states share the role of being risk factors for cardiovascular diseases. Chronic-aerobic exercise and/or reduction of body fat as well as medication are the options to lower blood pressure (BP whereas folic acid (FA) supplement is na efficient way to lower HyHcy. Thiazine a common diuretic used for high BP treatment is related to lower folic availability to the body.PURPOSE: To investigate the interactions of these BP lowering agents were investigated.METHODS: 69 hypertensive patients (HT): 141 15 mmHg/86 10 mmHg, 57 10 yrs old, 22 males and 47 females matched by sex, age and body composition with 50 normotensive subjects (NT): 130 10 mmHg (SBP) and 80 mmHg (DBP) all volunters for the study. After na initial (M0) assessment for medical, anthropometric, dietetic, blood chemists and V02max variables they started a 6 mo. Program of supervised physical exercise (SPE) composed by 80 min-session (60-70% V02max), 3-5 days/wk. The HT group (under BP medication) was divided in subgroups receiving ( HTT, n=32) or not (HTC,n=37) the thiazidic drug.Both HT subgroups were given orally 500 g/d of FA capsules, during 2 mo. In a crossover design with placebo (lactose),interpolated with a 2 mo. washout period. The assessments of BP (24 hours ambulatory BP measurements),food intake, body composition,blood chemists (including Hcy,folic acid and vitamin B12) were repeated every two-month (M0,M1 and M2).RESULTS:At M0 HT showed higher BP and Hcy (14 3 X 10,4 1,8 mol/L) than NT. Subgroups HTT and HTC were similar for all variables. Besides medicated 62% of HT showed uncontrolled BP. Six mo. of SPE downgraded the hypertensive status of HT patients without affecting significantly their body composition or blood chemistry,including Hcy. Folic acid supplementation (2 mo.) increased plasma folate and decreased HyHcy prevalence in HT from 11% (HTT) to 19% (HTC). However Hcy normalization occured only in HT that became normotensive. The remaining HT showed HyHcy downgraded to a borderline levels. The grater response of Hcy occurred with the higher plasma folate,both in the absence of thiazidic (HyHcy decreasing: HTC 71% > HTT 42%).CONCLUSIONS:The normalization of BP by SPE, FA supplementation and drugs was not followed neither by body-weight or general blood changes except by plasma Hcy normalization. SPE alone had no effect on Hcy. The presenceof thiazidic boostered the BP normalization but reduced the HyHcy. Supported by FAPESP and CNPq
INTRODUCTION
TREATMENTS RISK FACTORS
DISEASE
Physical Exercise
Essential Hypertensio
nAtheroscleroti
cCardiovascular
DiseaseHigh plasma Homocystein
e
Drugs
Folate Suppl.
Thiazidic
Body storage-folic acid
(-)
(-)
(-)
(-)
INTRODUCTION
- Hypertension and hyperhomocysteinemia (HyHcy) are risk factorsfor cardiovascular diseases, with potential interrelationship betweenboth factors.
- Physical exercises, reduction of body fat and drugs are the options to lower blood pressure (BP) whereas folic acid (FA) supplementationis the best way to reducing plasma homocysteine.
- Thiazidic has potential anti-folic acid bioavailability actions.
OBJECTIVE
To investigate the interactions of medication, physical exercise and folic acid supplementation as BP loweringagents in hypertensive subjects.
and the study was approved by the Research Ethics Committee of Botucatu Medical School
- UNESP
METHODS Blood hypertension diagnosis: - Clinical (digital OMRON, mod. HEM-413C) - 24 hours Ambulatory BP measurements (Spacelabs-Inc, mod.90207- 50)Anthropometry: - Body-weight and height (150 kg plataform scale -100g precision);- Body Mass Index (BMI) = kg/m2 (standards - WHO,2002)- Electrical Bioimpedance: fat-free mass (Segal et al,1988)- Waist circunference: inelastic tape (0,1cm).Standards: men<102 cm, women < 88 cm.
Plasma Assays:
- Homocysteine (Hcy) - HPLC method (Ubbink et al,1991)
- Folic Acid (FA) and B12 vitamin - Fluorimetric method
(Immulite-DPC,2000)
- Glucose, triglycerides, total and HDL-cholesterol
(Dry chemistry- Johnson & Johnson 750/950)
METHODS (cont.) Folate Supplementation (FS):
- 500 g of folic acid during 2 months, crossed over with lactose as placebo and 2 mo. of washout.
Supervised Physical Exercise Program (SPE):- Daily sessions of 80 min exercises: 10 min warm up, 40 min brisk walk (60-80% max HR/age), 20 min flexibility, 10 min relaxing; Statistical Analysis:
- Association among variables: x2 test corrected by Fisher exact test;
- Mean comparison between groups (Student t test for independent
variables);
- Mean comparison among intragroup moments (Student t test for
dependent variables);
- Significance level 5%
EXPERIMENTAL DESIGN M4washout
** **
G1 NTN=50
**
HTC (n=37)
M0 M2 M6 months
G2 HTN=69
HTT (n=32)
***
FAS
Placebo
Physical ExerciseG1 =control - normotensivesG2 HT= Hypertensive groupHTC= Hypertensive without taking thiazidicHTT= Hypertensive taking thiazidicFAS: Folate supplementation (500g/d)Placebo: lactose * Clinical and Ambulatory BP measurement** BP registry, anthropometric and biochemical assessments
RESULTS- Hypertensives (G2- HT) differed of normotensives (G1- NT) by their higher blood pressure (SBP and DBP) and higher plasma homocysteine levels(Table 1).
- At baseline (M0) 62% of hypertensives (HT) showed uncontrolled blood pressure (BP), mostly females (Fig. 1).
- Hypertensive subjects receiving (HTT) or not (HTC) thiazidic diuretic (TZN) as treatment differed only in plasma Hcy, being higher in HTT (Tables 2a and 2b).
- Physical exercise protocol (2 mo) decreased the prevalence of moderate (6%) and mild (9%) and increased the borderline (16%) hypertension degree (Fig.2)
RESULTS (cont.)
- Physical exercise protocol (2 mo) did not change significantly (M0/M1) neither body composition, blood pressure or plasma Hcy (Table 3).
- Folate supplements (FS) boostered the BP normalization by physical exercises (Table 4).
-The normalization of plasma homocysteine occurred only in normotyensives. On the other hand, the moderated homocysteinemia increases in the borderline (2/6) and mild (10/12) hypertensive patients and decrease in moderated hypertensive (Table 5).
- Folate supplements (FS) increased significantly the plasma folic acid in both thiazidic treated (HTT) and non-treated (HTC) hypertensives (Table 6).
- Folate supplements (FS) decreased the plasma Hcy mainly in hypertensive not receiving thiazidic (HTC) (Table 7).
Table 3. – Effect of physical exercise (PE) on the body composition, blood pressure and plasma Hcy levels of placebo and folic acid supplemented (FS) hypertensive subjects
RESULTS
8/55/8Normotensive
1/43/5Moderate
14/1715/18Mild
9/614/6Borderline
FSHT degrees Placebo
Hypertensive Groups
HT-hypertensive; FS-folate supplementation
Table 4. – Effect of folate supplementation (FS) for 2 months on the frequency of hypertension degrees (M1/M0)
Table 5 – Associations of hypertension degrees and plasma homocysteine estratification
PlasmaHomocysteine (mol/L)
Hypertension degrees
NT BD MILD MOD
Pré Pós Pré Pós Pré Pós Pré Pós
< 10 1 4 1 1 0 0 2 1
10 – 15 10 7 9 16 25 17 5 2
> 15 2 2 2 6 10 12 2 1
All 13 13 12 23 35 29 9 4
NT=normotensive; BD=borderline, MOD=moderate
RESULTS
7,2 2,5/9,2 2,8*
Folic acid
Hcy (mol/L)
HTC HTT
Placebo FS Placebo FS
15,5 3,8/13,3 2,2*
14,3 2,1/14,4 2,7
12,4 4,7/7,4 2,8*
7,0 2,5/ 8,6 3,8
14 2,4/17,3 4,3
13,2 2,4/14,9 3,3*
12,7 5/8,1 3,5*
* statistical significance ( p < 0,05)
Table 6. - Effect of folate supplementation (FS) for 2 months (M1/M0) on plasma homocysteine (Hcy) and folic acid of groups treated (HTT) or not (HTC) with thiazidic diuretic
RESULTS
4/01/1< 10
7/127/28> 15
21/2029/810-15
Hcy levels (mol/L)
Hypertensive Groups
HTT HTC
Hcy-- homocysteine
Table 7. – Effect of folate supplementation (FS) for 2 months (M1/M0) on the plasma homocysteine (Hcy) distribution in the presence (HTT) and absence of thiazidic (HTC)
CONCLUSIONS- The physical exercises downgraded the
hypertension severity by 31% without significant effects on plasma homocysteine,however blood pressure normalization occurred only in the presence of normal plasma homocysteine values.
- The folic acid supplementation (FAS) increased the plasma folate and reduced the hyperhomocysteine prevalence among hypertensives.
- The presence of thiazidic (HTT) lead to a lower response to folic acid supplementation (FAS),suggesting increased needs of FAS in the presence of this drug,
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