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Outcome comparison of cholesterol screening vs dietary advice: The clearest study
232 Implications of Regression Trial8 for Clinical Practice.
Wynn
H F Oliver Institute for Metabolic London, NW8 9SQ
Research,
Recent results of regression trials in patients with CBD indicate obstructive coronary lesions >50% respond most to LDL lowering. An implication is that reduction of raised LDL reduces obstructive lesions to a degree where the incidence of thrombosis is low. Commensurate improvement in blood flow and clinical events probably occurs, but the degree of absolute improvement in luminal diameter is small. Whether less fissuring of plaques with a reduction in sudden cardiac death will also occur has yet to be established. Lipid analysis of stable and unstable plaques will be presented. Regression of milder lesions may be much slower, possibly depending on their lipid composition, and in keeping with the 5-7 year delay in reduction of non-fatal myocardial infarction related to reduction of hypercholesterolaemia in primary prevention trials. While the prevention of the development of new lesions by calcium antagonists is encouraging, comparable reduction in clinical events has not yet hr?eIldnmonatrnted.
Free Communications TREATMENTOFSEVEREHYPERCHOLESTEROLEMIA ANDCORONARYHEARTDlSEASERYSlMVASTATIN ANDLDLAPHERKSIS(HELP)-EFFECTSONCORONARY LESIONS
&lFJJ. Pfalxcr B, Rcktor W, Lund G, Bcisicgcl U, Hamm CW. Gretcn H. Univcrsitits-Krankcnhaus Eppcndorf, Dep. of Inlcrnal Mcdicinc, Martinstr.52,2OGO Hamburg 20, FRG
Progression of coronary heart discasc (CHD) in patients with hypcrcholcstcrolcmia can bc rcduccd by lipid lowering Ihcrapy. In scvcrc hypcrcholcstcrolcmia maximal rcduclion of plasma cholesterol can bc achicvcd by additional LDL aphcrcsis. Therefore, 10 padcnts (6 males, 4 fcmalcs, mean age 45 yrs) with severe CHD and primary hypcrcholcstcrolcmia ( plasma cholesterol 437f69 mg/dl) wcrc trcatcd with a combined regimen of diet, simvastatin and intcrmittcnt LDL-aphcrcsis (HELP) for 2 years. Progression of coronary arlcry discasc was monitored by clinical evaluation, rcpcat angiography and szintigraphy. Results: Plasma LDL cholcstcrol (LDL chol)was rcduccd from 36258mg/dl al basclinc IO 138_+30mg/dl after 2 years ( LDL chol 88f21 mg/dl after LDL aphcrcsis, LDL chol 187+35 mg/dl bcforc next LDL aphcrcsis ), HDL chol incrcascd from 4h?rlO mg/dl 10 55f14mg/dl, and Lp(a) was rcduccd from 147?74 mg/dl at basclinc to 99?33 mg/dl (bctwccn aphcrcscs). No adverse clinical cvcnt occurred and clinical signs of ischcmia were unchanged. Stress-induced ischcmia (thallium-201 szinligraphy) was dccrcascd in 2 pu and incrcascd in 2 pLs. maximal heart rateprcssurc product slightly incrcascd (+8%). Quantitative computcrassistcd evaluation ol angiograms (6 pts, 57 scgmcnls were analyzed) showed rcgrcssion in g/57 scgmcnls (14%) and progression in 7/57 scgmcnh (12%).
OUTCOME COMPARISON OF CHOLESTEROL SCREENING VS DIETARY ADVICE: THE CLEAREST STUDY. MJ Brown, M Hughes,RWhite,J Ashby-Swain, D Truhvein, M Bailie, R Hopper and CR Molton Clinical PharmacologyUnit,University of Cambridge, Addenbrooke’s Hospital, Cambridge, CB2 2QQ Our objective is to compare the incidence of myocardial infarction (MI) during 5 years in 20,ooO subjects aged 4069 who are random&l to cholesterol (C) screening and appropriate treatment, and 20000 matched subjects who receive advice on healthy eating without C screening. The study is PROBE in design (prospective, randomised, open, with blind endpoint determination). Subjects with hypertension, diabetes or family history of MI under the age of 45 arc excluded. Over 16,000 subjects have so far been recruited during 2 years of invited screens in 28 general practices in East Anglia. Those subjects with an initial C >6.2 mrnol/L are re-screened after 2 months dietary treatment, after which 41% have reduced their C to <6.2 mmol/L. The best response to diet is in subjects with phenotypic FH. Drug treatment in the remainder, randomised according to both C and HDL, is (statin or fibrate) and/or (aspirin or vitamin E) with ‘no treatment’ controls for each. Of interest among the initial data, a multiple regression analysis of age, sex, BP, C, weight, height, BMI, waist/hip ratio and birthweight (recalled in 820 subjects) confirms that BP and C are negatively correlated with birthweight (pcorr=O. 10, p <0.02), but for C there is an additional negative correlation with height that accounts for more than half the correlation between C and BMI.
Wynn
H F Oliver Institute for Metabolic London, NW8 9SQ
Research,
Recent results of regression trials in patients with CBD indicate obstructive coronary lesions >50% respond most to LDL lowering. An implication is that reduction of raised LDL reduces obstructive lesions to a degree where the incidence of thrombosis is low. Commensurate improvement in blood flow and clinical events probably occurs, but the degree of absolute improvement in luminal diameter is small. Whether less fissuring of plaques with a reduction in sudden cardiac death will also occur has yet to be established. Lipid analysis of stable and unstable plaques will be presented. Regression of milder lesions may be much slower, possibly depending on their lipid composition, and in keeping with the 5-7 year delay in reduction of non-fatal myocardial infarction related to reduction of hypercholesterolaemia in primary prevention trials. While the prevention of the development of new lesions by calcium antagonists is encouraging, comparable reduction in clinical events has not yet hr?eIldnmonatrnted.
Free Communications TREATMENTOFSEVEREHYPERCHOLESTEROLEMIA ANDCORONARYHEARTDlSEASERYSlMVASTATIN ANDLDLAPHERKSIS(HELP)-EFFECTSONCORONARY LESIONS
&lFJJ. Pfalxcr B, Rcktor W, Lund G, Bcisicgcl U, Hamm CW. Gretcn H. Univcrsitits-Krankcnhaus Eppcndorf, Dep. of Inlcrnal Mcdicinc, Martinstr.52,2OGO Hamburg 20, FRG
Progression of coronary heart discasc (CHD) in patients with hypcrcholcstcrolcmia can bc rcduccd by lipid lowering Ihcrapy. In scvcrc hypcrcholcstcrolcmia maximal rcduclion of plasma cholesterol can bc achicvcd by additional LDL aphcrcsis. Therefore, 10 padcnts (6 males, 4 fcmalcs, mean age 45 yrs) with severe CHD and primary hypcrcholcstcrolcmia ( plasma cholesterol 437f69 mg/dl) wcrc trcatcd with a combined regimen of diet, simvastatin and intcrmittcnt LDL-aphcrcsis (HELP) for 2 years. Progression of coronary arlcry discasc was monitored by clinical evaluation, rcpcat angiography and szintigraphy. Results: Plasma LDL cholcstcrol (LDL chol)was rcduccd from 36258mg/dl al basclinc IO 138_+30mg/dl after 2 years ( LDL chol 88f21 mg/dl after LDL aphcrcsis, LDL chol 187+35 mg/dl bcforc next LDL aphcrcsis ), HDL chol incrcascd from 4h?rlO mg/dl 10 55f14mg/dl, and Lp(a) was rcduccd from 147?74 mg/dl at basclinc to 99?33 mg/dl (bctwccn aphcrcscs). No adverse clinical cvcnt occurred and clinical signs of ischcmia were unchanged. Stress-induced ischcmia (thallium-201 szinligraphy) was dccrcascd in 2 pu and incrcascd in 2 pLs. maximal heart rateprcssurc product slightly incrcascd (+8%). Quantitative computcrassistcd evaluation ol angiograms (6 pts, 57 scgmcnls were analyzed) showed rcgrcssion in g/57 scgmcnls (14%) and progression in 7/57 scgmcnh (12%).
OUTCOME COMPARISON OF CHOLESTEROL SCREENING VS DIETARY ADVICE: THE CLEAREST STUDY. MJ Brown, M Hughes,RWhite,J Ashby-Swain, D Truhvein, M Bailie, R Hopper and CR Molton Clinical PharmacologyUnit,University of Cambridge, Addenbrooke’s Hospital, Cambridge, CB2 2QQ Our objective is to compare the incidence of myocardial infarction (MI) during 5 years in 20,ooO subjects aged 4069 who are random&l to cholesterol (C) screening and appropriate treatment, and 20000 matched subjects who receive advice on healthy eating without C screening. The study is PROBE in design (prospective, randomised, open, with blind endpoint determination). Subjects with hypertension, diabetes or family history of MI under the age of 45 arc excluded. Over 16,000 subjects have so far been recruited during 2 years of invited screens in 28 general practices in East Anglia. Those subjects with an initial C >6.2 mrnol/L are re-screened after 2 months dietary treatment, after which 41% have reduced their C to <6.2 mmol/L. The best response to diet is in subjects with phenotypic FH. Drug treatment in the remainder, randomised according to both C and HDL, is (statin or fibrate) and/or (aspirin or vitamin E) with ‘no treatment’ controls for each. Of interest among the initial data, a multiple regression analysis of age, sex, BP, C, weight, height, BMI, waist/hip ratio and birthweight (recalled in 820 subjects) confirms that BP and C are negatively correlated with birthweight (pcorr=O. 10, p <0.02), but for C there is an additional negative correlation with height that accounts for more than half the correlation between C and BMI.