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M.578 Associations between physical activity and cardiovascular risk factors in young adults: The cardiovascular risk in young finns study
134
Miscellaneous
Mansego
45 Kb distributed in 18 exons. To date, more than 850 different mutations have been described. Clinical diagnosis of FH is complex and uncertain, only genetic diagnostic is unequivocal. Due to LDLr gene structural characteristics (length, GC-rich, Alu elements) there is a huge number of different types of mutations that make its analysis difficult. We have developed a method that allows the detection of point mutations as well as short and large man'angements. Point mutations and short rearrangements were analyzed by 8 multiplex-PCR reactions performed simultaneously on an Applied Biosystems GeneAmp 9700, followed by automatic capillary sequencing performed on an Amersham Pharl'nacia MegaBACE 1000. Sequence analysis was computel~assisted. All steps have been optimized to increase speed and productivity and to decrease costs. Large rearrangements were analyzed by LA-PCR (Long and Accurate Polymerase Chain Reaction). The whole LDLr gene was amplified simultaneusly into 5 fi'agments and they were analyzed on agarose 0,5% gel electrophomsis in order to search for size and/or intensity changes. In conclusion, using an Applied Biosystems GeneAmp 9700 and an Amersham Pharl'nacia MegaBACE 1000 we ale able to analyze the enth'e LDLr gene in 12 patients daily.
•]
MECHANISMS IMPLICATED IN THE OXIDATIVE STRESS OF HYPERTENSION
M.L. Mansego, S. Blesa, V. Gonz lez, M.C. Torrno, O. Espinosa, G. S ez, F.J. Chaves, J. Redon. Unidad Mixta de Investigaci n-Lab. Estudios
Gen ticos; Hospital (2l nico Universitario de Valencia; Depto. de Bioqu mica y Biolog a Molecular; Facultad de Medicina; Universidad de Valencia; Servicio de Medicina Interna, Hospital (2l nico Universitario de Valencia, Valencia, Spain An increase of oxidative staess and a reduction in the antioxidant enzyme activities have been demonsta'ated in hypertensive subjects. Whether or not the low antioxidant enzyme activities are primary or secondary to theft" inactivation by oxidative s~ess has not been established. Patients and Methods: Mononuclear cells were extracted fi'om peripheral blood and GSH, GSSG and activity catalase, Cu/Zn SOD, MnSOD were measured. The mRNA levels were measured using real-time quantitative RT-PCR and normalized to GAPDH mRNA. Results: Hypertensive subjects shown an increase in oxidative s~ess parameters and a decrease in antioxidant enzyme activity. The mRNA of Cu/Zn SOD, MnSOD, as well as of GSS and GSR, were also significantly decreased in cases. The relationship between the enzymatic activity and the mRNA expression indicates a blunted capacity to increase the mRNA generation despite the enzymatic deficiency. After three months of antihypertensive ~eatment, the increment in enzymatic antioxidant activity was followed by a further decrease in the mRNA expression (Table 1). Conn'ols (n=12) GSS GSR CAT MnSOD Cu/ZnSOD
18±7" 52 ± 20 17 ± 2 230 ± 60* 35 ± 10"
Hypertensives baseline (n=48)
Hypertensives during n'eatment (n=33)
9±2 36 ± 10 18 ± 2 158 ± 30 22 ±10
2 ± 1"* 7 ± 1"* 16 ± 2 56 ± 10"* 8 ± 2**
Data as x 103; *'/)<0.05 between hypertensivesand controls; **'/)<0.05between baseline and treatment Conclusion: In hypertension, the low enzymatic antioxidant activity is not only consequence of consumption due to the increased reactive oxygen species but also is produced by an impafl-ment on the capacity to generate enough antioxidant enzymes. A better understanding of the mechanisms implicated in the oxidative stress may help us in to define therapeutic targets to reduce hypertension-induced organ damage.
~ 8 ]
ASSOCIATIONS BETWEEN PHYSICAL ACTIVITY AND CARDIOVASCULAR RISK FACTORS IN YOUNG ADULTS: THE CARDIOVASCULAR RISK IN YOUNG FINNS STUDY
K. Mansikkaniemi, J. Viikari, R. Telama, J. Marniemi, O. Raitakari.
University of Turku, University of Jyv skyl , Social Insurance Institution of Finland, Turku, Finland Objective Physical activity may reduce the risk of coronary heart disease (CHD) by inducing beneficial changes in risk factors. The objective of this
study was to analyse the associations between physical activity and CHD risk factors in young adults. Methods As a part of the longitudinal follow-up study, we measured waist cfl'cumference, blood pressure, serum lipids, C-reactive protein (CRP), homocysteine and insulin in 2,031 subjects aged 24 to 39 years. Daily smoking was assessed by a questionnafl'e and hypertension was defined as blood pressure over 130/85 mmHg. The level of physical activity (PA) was estimated by assessing the duration, intensity and fiequency of leisure-time PA. Results In both sexes, PA was strongly and inversely associated with waist circumference (p<0.0001) and age (p<0.0001). After adjustment for waist and age, PA remained inversely associated with smoking (women p=0.008; men p<0.0001) and dfl'ectly with serum high density lipoprotein cholesterol (women p<0.05; men p=0.002). In men, but not in women, PA associated also inversely with serum insulin (p<0.0001) and glucose (p=0.005). In women, but not in men, PA associated inversely with CRP (p<0.05). PA was not significantly associated with serum homocysteine levels in either sex. Conclusion We conclude that leisure-time PA is associated with a favourable CHD risk factor profile both among men and women during early adulthood in dose-related manner. These results are consistent with the idea that the beneficial effects of PA on CHD risk are mediated by influences on risk factors. IMMEDIATE EFFECT ON OXIDATIVE M•.579] SIMVASTATIN STRESS IN HYPERLIPIDAEMIC SUBJECTS M. Marketou, E. Zacharis, D. Nikitovits, E. Ganotakis, G. Kochiadakis, E. Simantfl-akis, P. Vardas. Cardiology and Internal Medicine Departments,
Heraklion University Hospital, Heraklion, Greece Introduction: Long-terrn statin therapy has a beneficial effect on lipoprotein oxidation, one of the first steps in atherogenesis, however the time period during which the benefits become effective have not yet been clarified. We assessed the effect of simvastatin on oxidative s~ess in hyperlipidaemic patients early after ~eatrnent initiation. Methods: Twenty-five hyperlipidaemic subjects (15 men, aged 49 -4-7years, total cholesterol> 239mg/dl, LDL> 160rag/all) were randomized to receive either simvastatin or placebo. None had diabetes, hypertension, coronary disease or any inflammatory disease. Fifteen patients received 80rag simvastatin on the first day, followed by 40rag/day, while ten patients received placebo. Blood samples were taken before, and 2 hours, 24 hours and 7 days after simvastatin administa'ation. Lipid peroxides (analyzed by a photometa'ic assay, Oxystat, Biomedica), total and LDL-cholesterol were evaluated each time. Results: Lipid peroxides (l~mol/L) were significantly reduced immediately after the first dosage of simvastatin:
Baseline Simvastatin Placebo
2 hours
376.5±99.5 329.7±90.8* 363.4±76.7 368±83.8
24 hours
7 days
310.1±69.2" 382±96.5
306.8±100.4" 380± 110.2
*p<0.005 There was a trend, though not significant, towards decreased cholesterol during the study period (cholesterol: fi'om 269.2-4-47 mg/dl to 251.7-4-94.9 mg/dl, p:0.06, LDL: fi'om 186.2-4-68 mg/dl to 178.4-4-81.1 mg/dl, p:NS). Conelusions:Simvastatin administration in hyperlipidaemic subjects resuits in the immediate reduction of oxidative stress upon initiation of treatment, independently of the hyperlipidaemic effect of the drug.
•0•
ANTIOXIDANT VITAMINS (A, E AND C) IN THE RISK PROFILE OF CARDIOVASCULAR DISEASE IN DYSLIPIDEMIC PATIENTS
M. Marquez, C. Yepez, S. Rosalia, M. Tolxes, M. Rincon, M. Mu oz, M. Leal, R. Oviedo. University of Carabobo, Valencia, Venezuela As part of heart disease risk profile together with classic risk factors (CRF), impact of antioxidants as non-classic risk factor (NCRF) has been little studied in Venezuela. With the aim of testing antioxidant vitamins status, anthropometa'y, plasma lipids and serum levels of vitamins alpha tocopherol, retinol (by HPLC) and ascorbic acid, were evaluated 40 dyslipidemic adults (DA) and 26 conta'ols (CT). Body mass index (BMI) was high in half of DA, 80% showed a high risk level according to waist/hip relation (W/H),
74th EAS Congress, 17-20 April 2004, Seville, Spain
Miscellaneous
Mansego
45 Kb distributed in 18 exons. To date, more than 850 different mutations have been described. Clinical diagnosis of FH is complex and uncertain, only genetic diagnostic is unequivocal. Due to LDLr gene structural characteristics (length, GC-rich, Alu elements) there is a huge number of different types of mutations that make its analysis difficult. We have developed a method that allows the detection of point mutations as well as short and large man'angements. Point mutations and short rearrangements were analyzed by 8 multiplex-PCR reactions performed simultaneously on an Applied Biosystems GeneAmp 9700, followed by automatic capillary sequencing performed on an Amersham Pharl'nacia MegaBACE 1000. Sequence analysis was computel~assisted. All steps have been optimized to increase speed and productivity and to decrease costs. Large rearrangements were analyzed by LA-PCR (Long and Accurate Polymerase Chain Reaction). The whole LDLr gene was amplified simultaneusly into 5 fi'agments and they were analyzed on agarose 0,5% gel electrophomsis in order to search for size and/or intensity changes. In conclusion, using an Applied Biosystems GeneAmp 9700 and an Amersham Pharl'nacia MegaBACE 1000 we ale able to analyze the enth'e LDLr gene in 12 patients daily.
•]
MECHANISMS IMPLICATED IN THE OXIDATIVE STRESS OF HYPERTENSION
M.L. Mansego, S. Blesa, V. Gonz lez, M.C. Torrno, O. Espinosa, G. S ez, F.J. Chaves, J. Redon. Unidad Mixta de Investigaci n-Lab. Estudios
Gen ticos; Hospital (2l nico Universitario de Valencia; Depto. de Bioqu mica y Biolog a Molecular; Facultad de Medicina; Universidad de Valencia; Servicio de Medicina Interna, Hospital (2l nico Universitario de Valencia, Valencia, Spain An increase of oxidative staess and a reduction in the antioxidant enzyme activities have been demonsta'ated in hypertensive subjects. Whether or not the low antioxidant enzyme activities are primary or secondary to theft" inactivation by oxidative s~ess has not been established. Patients and Methods: Mononuclear cells were extracted fi'om peripheral blood and GSH, GSSG and activity catalase, Cu/Zn SOD, MnSOD were measured. The mRNA levels were measured using real-time quantitative RT-PCR and normalized to GAPDH mRNA. Results: Hypertensive subjects shown an increase in oxidative s~ess parameters and a decrease in antioxidant enzyme activity. The mRNA of Cu/Zn SOD, MnSOD, as well as of GSS and GSR, were also significantly decreased in cases. The relationship between the enzymatic activity and the mRNA expression indicates a blunted capacity to increase the mRNA generation despite the enzymatic deficiency. After three months of antihypertensive ~eatment, the increment in enzymatic antioxidant activity was followed by a further decrease in the mRNA expression (Table 1). Conn'ols (n=12) GSS GSR CAT MnSOD Cu/ZnSOD
18±7" 52 ± 20 17 ± 2 230 ± 60* 35 ± 10"
Hypertensives baseline (n=48)
Hypertensives during n'eatment (n=33)
9±2 36 ± 10 18 ± 2 158 ± 30 22 ±10
2 ± 1"* 7 ± 1"* 16 ± 2 56 ± 10"* 8 ± 2**
Data as x 103; *'/)<0.05 between hypertensivesand controls; **'/)<0.05between baseline and treatment Conclusion: In hypertension, the low enzymatic antioxidant activity is not only consequence of consumption due to the increased reactive oxygen species but also is produced by an impafl-ment on the capacity to generate enough antioxidant enzymes. A better understanding of the mechanisms implicated in the oxidative stress may help us in to define therapeutic targets to reduce hypertension-induced organ damage.
~ 8 ]
ASSOCIATIONS BETWEEN PHYSICAL ACTIVITY AND CARDIOVASCULAR RISK FACTORS IN YOUNG ADULTS: THE CARDIOVASCULAR RISK IN YOUNG FINNS STUDY
K. Mansikkaniemi, J. Viikari, R. Telama, J. Marniemi, O. Raitakari.
University of Turku, University of Jyv skyl , Social Insurance Institution of Finland, Turku, Finland Objective Physical activity may reduce the risk of coronary heart disease (CHD) by inducing beneficial changes in risk factors. The objective of this
study was to analyse the associations between physical activity and CHD risk factors in young adults. Methods As a part of the longitudinal follow-up study, we measured waist cfl'cumference, blood pressure, serum lipids, C-reactive protein (CRP), homocysteine and insulin in 2,031 subjects aged 24 to 39 years. Daily smoking was assessed by a questionnafl'e and hypertension was defined as blood pressure over 130/85 mmHg. The level of physical activity (PA) was estimated by assessing the duration, intensity and fiequency of leisure-time PA. Results In both sexes, PA was strongly and inversely associated with waist circumference (p<0.0001) and age (p<0.0001). After adjustment for waist and age, PA remained inversely associated with smoking (women p=0.008; men p<0.0001) and dfl'ectly with serum high density lipoprotein cholesterol (women p<0.05; men p=0.002). In men, but not in women, PA associated also inversely with serum insulin (p<0.0001) and glucose (p=0.005). In women, but not in men, PA associated inversely with CRP (p<0.05). PA was not significantly associated with serum homocysteine levels in either sex. Conclusion We conclude that leisure-time PA is associated with a favourable CHD risk factor profile both among men and women during early adulthood in dose-related manner. These results are consistent with the idea that the beneficial effects of PA on CHD risk are mediated by influences on risk factors. IMMEDIATE EFFECT ON OXIDATIVE M•.579] SIMVASTATIN STRESS IN HYPERLIPIDAEMIC SUBJECTS M. Marketou, E. Zacharis, D. Nikitovits, E. Ganotakis, G. Kochiadakis, E. Simantfl-akis, P. Vardas. Cardiology and Internal Medicine Departments,
Heraklion University Hospital, Heraklion, Greece Introduction: Long-terrn statin therapy has a beneficial effect on lipoprotein oxidation, one of the first steps in atherogenesis, however the time period during which the benefits become effective have not yet been clarified. We assessed the effect of simvastatin on oxidative s~ess in hyperlipidaemic patients early after ~eatrnent initiation. Methods: Twenty-five hyperlipidaemic subjects (15 men, aged 49 -4-7years, total cholesterol> 239mg/dl, LDL> 160rag/all) were randomized to receive either simvastatin or placebo. None had diabetes, hypertension, coronary disease or any inflammatory disease. Fifteen patients received 80rag simvastatin on the first day, followed by 40rag/day, while ten patients received placebo. Blood samples were taken before, and 2 hours, 24 hours and 7 days after simvastatin administa'ation. Lipid peroxides (analyzed by a photometa'ic assay, Oxystat, Biomedica), total and LDL-cholesterol were evaluated each time. Results: Lipid peroxides (l~mol/L) were significantly reduced immediately after the first dosage of simvastatin:
Baseline Simvastatin Placebo
2 hours
376.5±99.5 329.7±90.8* 363.4±76.7 368±83.8
24 hours
7 days
310.1±69.2" 382±96.5
306.8±100.4" 380± 110.2
*p<0.005 There was a trend, though not significant, towards decreased cholesterol during the study period (cholesterol: fi'om 269.2-4-47 mg/dl to 251.7-4-94.9 mg/dl, p:0.06, LDL: fi'om 186.2-4-68 mg/dl to 178.4-4-81.1 mg/dl, p:NS). Conelusions:Simvastatin administration in hyperlipidaemic subjects resuits in the immediate reduction of oxidative stress upon initiation of treatment, independently of the hyperlipidaemic effect of the drug.
•0•
ANTIOXIDANT VITAMINS (A, E AND C) IN THE RISK PROFILE OF CARDIOVASCULAR DISEASE IN DYSLIPIDEMIC PATIENTS
M. Marquez, C. Yepez, S. Rosalia, M. Tolxes, M. Rincon, M. Mu oz, M. Leal, R. Oviedo. University of Carabobo, Valencia, Venezuela As part of heart disease risk profile together with classic risk factors (CRF), impact of antioxidants as non-classic risk factor (NCRF) has been little studied in Venezuela. With the aim of testing antioxidant vitamins status, anthropometa'y, plasma lipids and serum levels of vitamins alpha tocopherol, retinol (by HPLC) and ascorbic acid, were evaluated 40 dyslipidemic adults (DA) and 26 conta'ols (CT). Body mass index (BMI) was high in half of DA, 80% showed a high risk level according to waist/hip relation (W/H),
74th EAS Congress, 17-20 April 2004, Seville, Spain