- Email: [email protected]
C-reactive protein and family history of myocardial infarction
Thursday, 27 May 1999 Workshop: Risk factors for coronary heart disease and stroke and prevention strategies of any confounding differences between the treatment groups on-treatment in blood pressure, smoking levels or in any other major risk factor. WOSCOPS was supported by a grant from the Bristol-Myers Squibb Pharmaceutical Research Institute.
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overlap. Subsequent ischaemic event rates were estimated for each vascular involvement pattern. Results: More than one vascular bed was involved in 34.4% of patients. CVD risk (MI, ischaemic stroke, vascular death) was 25% higher with two beds involved, versus one, and 51% higher with involvement in all three beds. In these high-risk populations, application o f the 8.7% relative risk reduction observed with clopidogrel in CAPRIE translates to an estimated 13 and 16 events prevented, respectively, per 1,000 PY over aspirin. Conclusion: Involvement of multiple vascular beds is common in actual practice and these patients have a much higher risk of subsequent CVD events. This needs to be taken into account when evaluating a new therapy as it has a major impact on the benefits that a given relative risk reduction yields. m
C-REACTIVE PROTEIN AND FAMILY HISTORY MYOCARDIAL INFARCTION
References
OF
M. Margaglione, G. Cappucci, D. Colaizzo, G. Vecchione, E. Grandone, G. Di Minno. Unita' di Aterosclerosi e Trombosi. LR.C.C.S. "Casa Sollievo
[1] J Shepherd e! al. NEJM 1995; 333:1301-1307 [2] F M Sacks et al. Circulation 1998; 97:1446-1452
della Sofferenza", S. Giovanni Rotondo; lstituto di Medicina lnterna e Geriatria. Universitd di Palermo, Italy
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3 m
CORONARY ARTERY DISEASE IN FAMILIAL COMBINED HYPERLIPIDEMIA (FCHL) PROBANDS AND THEIR RELATIVES C. Pette, T.W.A. de Bruin. Department of Medicine. Academic Hospital
Maastricht; Cardiovascular Research Institute, Maastricht Universi~., The Netherlands FCHL is a complex genetic disease with a seriously increased risk on coronary artery disease (CAD). However, quantitative data on the risk of CAD in FCHL relatives are lacking. Therefore, the clinical consequences for relatives of FCHL probands remain unclear. In the present cross-sectional study, 18 unrelated Dutch probands were identified with a primary combined hyperlipidemia (hypercholesterolemia and hypertriglyceridemia), at least one first degree relative with a different hyperlipidemic phenotype and a positive family history of premature CAD. Subsequently, 109 first degree relatives, I11 second degree relatives and 175 spouses were identified. In these relatives, the presence of CAD was evaluated and an extensive fasting lipid and lipoprotein profile was obtained, in combination with measurements of insulin and glucose plasma concentrations. CAD was defined as a documented history of myocardial infarction, bypass surgery or angioplasty. The group of spouses was used as an environmental- and diet matched control group. Plasma lipid and glucose traits were invariably elevated in probands and first degree relatives, compared to spouses. Second degree relatives showed normal traits, but were younger then spouses (35+1.6 y in second degree relatives versus 48+1.2 y in spouses, P < 0.0001) Kaplan-Meier curves showed that not only FCHL probands, but also firstand second relatives had a markedly reduced CAD-free life-span (logrank versus spouses: P < 0.01, P < 0.001 and P = 0.03 respectively). After adjusting for age and gender, probands showed an odds-ratio (OR) of 15.2 (P < 0.0001 ) compared to spouses. The OR was 6.2 for first degree relatives (P = 0.0003) and 3.1 for second degree relatives (P = 0.07). The OR for CAD in all relatives combined was 5.5 (P = 0.0005), excluding probands. These data show that not only FCHL probands, but also first- and second degree relatives have a severely increased risk for CAD. We therefore conclude that after identifying an FCHL proband as decribed, it is of major importance to screen first and second degree relatives for risk factors and to treat them at an early stage with lipid lowering agents. INVOLVEMENT OF MULTIPLE VASCULAR BEDS, CVD RISK, AND THE BENEFITS OF PREVENTION J.J. Carol., K. Migliaccio-Walle~, I. Thizon-de Gaulle 2, A.A. Coniglio3, H. Kelley 1. tCara Research," 3Bristol-Myers Squibb, USA; 2Sanofi, France
Background: CVD risk has been studied mainly in relation to a patient's most recent event. Most clinical trials of secondary prevention of CVD enroll patients at an arbitrary point in their disease. In CAPR1E, randomization was according to the most recent manifestation of CVD, yet fully understanding a new therapy's impact requires knowledge of the effect of involvement o f multiple vascular beds on CVD risk. Methods: Records back to 1980 for all 12,931 patients identified in the CAPRA study were evaluated to determine extent of vascular disease
Background: The relevance of elevated levels of C-reactive protein in cardiovascular disease is gaining increasing recognition. A family history of coronary artery disease is a major determinant of coronary artery disease in the offspring. We have investigated the relationships between C-reactive protein levels and a family history of myocardial infarction in a cohort of 999 apparently healthy individuals. Methods and Results: We have measured C-reactive protein, fibrinogen, plasminogen activator inhibitor-l, total cholesterol, triglycerides and some genetic polymorphisms: plasminogen activator inhibitor-I (4G/5G), fibrinogen (Bl~-chain G- > A-455), and angiotensin-converting enzyme (I/D). Clinical data were collected by a WHO-modified questionnaire for cardiovascular disease. When compared to subjects without (n = 838), subjects whose first-degree relatives had suffered from a myocardial infarction (n = 161) had elevated total plasma cholesterol (p < 0.001) and median age (p = 0.001); were more often homozygotes for the deleted allele (4G/4G) of the plasminogen activator inhibitor-I gene (p = 0.005) and exhibited raised plasma fibrinogen (p < 0.003), and C-reactive protein levels > 0.33 mg/L (p = 0.005). In a multiple logistic regression analysis, age (odds ratio, 1.03 [95 percent confidence interval, 1.00 to 1.05]), total cholesterol (odds ratio, 1.26 [95 percent confidence interval, 1.05 to 1.52]), plasminogen activator inhibitor-I 4G/4G (odds ratio, 1.66 [95 percertt confidence interval, 1.15 to 2.39]), and C-reactive protein levels > 0.33 mg/L (odds ratio, 1.91 [95 percent confidence interval, 1.13 to 3.21]), were all independently associated with a positive family history. Conclusions: Raised levels of C-reactive protein independently identify the offspring of patients with a myocardial infarction. LIPIDS AND OTHER RISK FACTORS FOR CORONARY HEART DISEASE IN TYPE 2 DIABETES MELLITUS D.D. Trifunovic-Zamaklar t , S. Kapor2, A.D. Ristic I , D. Simeunovic 1, PM. Seferovic 1, B. Trifunovic. llnstitutefor Cardiovascular disease,
Belgrade, 21NER Zemun, Yugoslavia Lipid profile risky for coronary heart disease (CHD) is frequently present in type2 Diabetes. The aim of this study was to compare serum lipids, lipid peroxidation and insulin level (IL) in Type 2 diabetics with and without CHD, in period of gnod metabolic control(HbAlc<8%).lnvestigation was performed in 25 patients without CHD (groupA) and in 27 patients with CHD(groupB).Groups were similar in ages o f patients, duration o f diabetes and in sex ratio. Triglycerides (TG-mmol/1), total cholesterol (TCh-mmolfl) and HDL cholesterol (HDLChmmol/l) were measured by enzymatic methods. LDL cholesterol (LDLChmmol/I) was calculated. Lp(a) (nmol/ml) was determined by immunonephelometry and IL(mU/I) by RIA.Lipid peroxidation (LP- nmol/ml) were estimated by colorimetric method.TG were elevated in both groups but without significant differences(groupA vs group B:2.43 +/-0.15 vs.2.68 +/0.18, p>0.05).We founded significant higher TCh in group B (7.25+/-0.14) compared with group CA 6.38+/-0.15, p<0.05) as well as significant higher LDLCh in group B (4.85+/- 0.12)than in group A (3.68+/-0.20). HDLCh was significantly lower in patients with CHD (Group A vs Group B: 1.42 +/-0.05 vs. 1.1 i+/-0.03, p<0.05). Also, in diabetics with CHD Lp(a) was considerably higher (Group A vs Group B: 0.24+/- 0.04 vs 0.36+/-0.03,
71st EAS Congress and Satellite Symposia
[~al)
17
overlap. Subsequent ischaemic event rates were estimated for each vascular involvement pattern. Results: More than one vascular bed was involved in 34.4% of patients. CVD risk (MI, ischaemic stroke, vascular death) was 25% higher with two beds involved, versus one, and 51% higher with involvement in all three beds. In these high-risk populations, application o f the 8.7% relative risk reduction observed with clopidogrel in CAPRIE translates to an estimated 13 and 16 events prevented, respectively, per 1,000 PY over aspirin. Conclusion: Involvement of multiple vascular beds is common in actual practice and these patients have a much higher risk of subsequent CVD events. This needs to be taken into account when evaluating a new therapy as it has a major impact on the benefits that a given relative risk reduction yields. m
C-REACTIVE PROTEIN AND FAMILY HISTORY MYOCARDIAL INFARCTION
References
OF
M. Margaglione, G. Cappucci, D. Colaizzo, G. Vecchione, E. Grandone, G. Di Minno. Unita' di Aterosclerosi e Trombosi. LR.C.C.S. "Casa Sollievo
[1] J Shepherd e! al. NEJM 1995; 333:1301-1307 [2] F M Sacks et al. Circulation 1998; 97:1446-1452
della Sofferenza", S. Giovanni Rotondo; lstituto di Medicina lnterna e Geriatria. Universitd di Palermo, Italy
i
i
C [
3 m
CORONARY ARTERY DISEASE IN FAMILIAL COMBINED HYPERLIPIDEMIA (FCHL) PROBANDS AND THEIR RELATIVES C. Pette, T.W.A. de Bruin. Department of Medicine. Academic Hospital
Maastricht; Cardiovascular Research Institute, Maastricht Universi~., The Netherlands FCHL is a complex genetic disease with a seriously increased risk on coronary artery disease (CAD). However, quantitative data on the risk of CAD in FCHL relatives are lacking. Therefore, the clinical consequences for relatives of FCHL probands remain unclear. In the present cross-sectional study, 18 unrelated Dutch probands were identified with a primary combined hyperlipidemia (hypercholesterolemia and hypertriglyceridemia), at least one first degree relative with a different hyperlipidemic phenotype and a positive family history of premature CAD. Subsequently, 109 first degree relatives, I11 second degree relatives and 175 spouses were identified. In these relatives, the presence of CAD was evaluated and an extensive fasting lipid and lipoprotein profile was obtained, in combination with measurements of insulin and glucose plasma concentrations. CAD was defined as a documented history of myocardial infarction, bypass surgery or angioplasty. The group of spouses was used as an environmental- and diet matched control group. Plasma lipid and glucose traits were invariably elevated in probands and first degree relatives, compared to spouses. Second degree relatives showed normal traits, but were younger then spouses (35+1.6 y in second degree relatives versus 48+1.2 y in spouses, P < 0.0001) Kaplan-Meier curves showed that not only FCHL probands, but also firstand second relatives had a markedly reduced CAD-free life-span (logrank versus spouses: P < 0.01, P < 0.001 and P = 0.03 respectively). After adjusting for age and gender, probands showed an odds-ratio (OR) of 15.2 (P < 0.0001 ) compared to spouses. The OR was 6.2 for first degree relatives (P = 0.0003) and 3.1 for second degree relatives (P = 0.07). The OR for CAD in all relatives combined was 5.5 (P = 0.0005), excluding probands. These data show that not only FCHL probands, but also first- and second degree relatives have a severely increased risk for CAD. We therefore conclude that after identifying an FCHL proband as decribed, it is of major importance to screen first and second degree relatives for risk factors and to treat them at an early stage with lipid lowering agents. INVOLVEMENT OF MULTIPLE VASCULAR BEDS, CVD RISK, AND THE BENEFITS OF PREVENTION J.J. Carol., K. Migliaccio-Walle~, I. Thizon-de Gaulle 2, A.A. Coniglio3, H. Kelley 1. tCara Research," 3Bristol-Myers Squibb, USA; 2Sanofi, France
Background: CVD risk has been studied mainly in relation to a patient's most recent event. Most clinical trials of secondary prevention of CVD enroll patients at an arbitrary point in their disease. In CAPR1E, randomization was according to the most recent manifestation of CVD, yet fully understanding a new therapy's impact requires knowledge of the effect of involvement o f multiple vascular beds on CVD risk. Methods: Records back to 1980 for all 12,931 patients identified in the CAPRA study were evaluated to determine extent of vascular disease
Background: The relevance of elevated levels of C-reactive protein in cardiovascular disease is gaining increasing recognition. A family history of coronary artery disease is a major determinant of coronary artery disease in the offspring. We have investigated the relationships between C-reactive protein levels and a family history of myocardial infarction in a cohort of 999 apparently healthy individuals. Methods and Results: We have measured C-reactive protein, fibrinogen, plasminogen activator inhibitor-l, total cholesterol, triglycerides and some genetic polymorphisms: plasminogen activator inhibitor-I (4G/5G), fibrinogen (Bl~-chain G- > A-455), and angiotensin-converting enzyme (I/D). Clinical data were collected by a WHO-modified questionnaire for cardiovascular disease. When compared to subjects without (n = 838), subjects whose first-degree relatives had suffered from a myocardial infarction (n = 161) had elevated total plasma cholesterol (p < 0.001) and median age (p = 0.001); were more often homozygotes for the deleted allele (4G/4G) of the plasminogen activator inhibitor-I gene (p = 0.005) and exhibited raised plasma fibrinogen (p < 0.003), and C-reactive protein levels > 0.33 mg/L (p = 0.005). In a multiple logistic regression analysis, age (odds ratio, 1.03 [95 percent confidence interval, 1.00 to 1.05]), total cholesterol (odds ratio, 1.26 [95 percent confidence interval, 1.05 to 1.52]), plasminogen activator inhibitor-I 4G/4G (odds ratio, 1.66 [95 percertt confidence interval, 1.15 to 2.39]), and C-reactive protein levels > 0.33 mg/L (odds ratio, 1.91 [95 percent confidence interval, 1.13 to 3.21]), were all independently associated with a positive family history. Conclusions: Raised levels of C-reactive protein independently identify the offspring of patients with a myocardial infarction. LIPIDS AND OTHER RISK FACTORS FOR CORONARY HEART DISEASE IN TYPE 2 DIABETES MELLITUS D.D. Trifunovic-Zamaklar t , S. Kapor2, A.D. Ristic I , D. Simeunovic 1, PM. Seferovic 1, B. Trifunovic. llnstitutefor Cardiovascular disease,
Belgrade, 21NER Zemun, Yugoslavia Lipid profile risky for coronary heart disease (CHD) is frequently present in type2 Diabetes. The aim of this study was to compare serum lipids, lipid peroxidation and insulin level (IL) in Type 2 diabetics with and without CHD, in period of gnod metabolic control(HbAlc<8%).lnvestigation was performed in 25 patients without CHD (groupA) and in 27 patients with CHD(groupB).Groups were similar in ages o f patients, duration o f diabetes and in sex ratio. Triglycerides (TG-mmol/1), total cholesterol (TCh-mmolfl) and HDL cholesterol (HDLChmmol/l) were measured by enzymatic methods. LDL cholesterol (LDLChmmol/I) was calculated. Lp(a) (nmol/ml) was determined by immunonephelometry and IL(mU/I) by RIA.Lipid peroxidation (LP- nmol/ml) were estimated by colorimetric method.TG were elevated in both groups but without significant differences(groupA vs group B:2.43 +/-0.15 vs.2.68 +/0.18, p>0.05).We founded significant higher TCh in group B (7.25+/-0.14) compared with group CA 6.38+/-0.15, p<0.05) as well as significant higher LDLCh in group B (4.85+/- 0.12)than in group A (3.68+/-0.20). HDLCh was significantly lower in patients with CHD (Group A vs Group B: 1.42 +/-0.05 vs. 1.1 i+/-0.03, p<0.05). Also, in diabetics with CHD Lp(a) was considerably higher (Group A vs Group B: 0.24+/- 0.04 vs 0.36+/-0.03,
71st EAS Congress and Satellite Symposia