4. Análisis e interpretación de resultados de investigación
4.1. Desarrollo histórico de laexportación lanera
A group o f 17 unrelated hyperiipidaemic individuals on whom fractional catabolic rate o f LDL studies have been determined by in vivo turnover studies o f autologous LDL (Shepherd et al., 1979). Familial hypercholesterolaemia was excluded on the basis o f standard criteria, and the patients have been described in Demant et al, (1988) (Section 1.5.4).
2.2.2 Sheffield
A group o f 22 unrelated men on whom fractional catabolic rate o f LDL had also been performed (Turner et al. 1984, International Collaborative Study Group, 1986). Familial hypercholesterolaemia was excluded on the basis o f standard criteria, these individuals have been described in Houlston et al. (1988) (Section 1.5.4).
2.2.3 North Karelia . Finland
A group o f 89 unrelated men and women, with no history o f hyperlipidaemia, from a rural community in North Karelia, Finland. This population has been very stable for several hundred years with no influence o f Swedish speaking individuals. They have been described in detail elsewhere (Ehnholm et al. 1982, 1984, Kuusi et al. 1985). Ag phenotyping, and apoB RFLP genotyping have also been previously described (Xu et al. 1989, Tikkanen et al. 1989).
2.2.4 Finnish
A second group o f 24 Ag phenotyped, unrelated Finnish individuals was also examined. Phenotyping and apoB genotyping has been described by Dunning et al. (1988).
2.2.5 Swedish controls
patient group described below. These individuals were free o f symptoms and clinical signs o f CAD. Data on lipid, lipoprotein, apoprotein, haemostatic and metabolic variables have been presented elsewhere (Hamsten et al. 1986b, 1987). ApoB genotyping has been described in Peacock et al. (1993J. One individual with a serum triglyceride level > 3.0mM was excluded from the lipid and lipoprotein analyses. Mean serum levels o f certain lipid traits and apoB together with the amount o f phenotypic variance explained by age and BMI are given in Table 2 .2.5.
Table 2.2.5 Mean serum lipid and lipoprotein traits and phenotypic variance explained bv age and BMI in the Swedish control group.
Mean ( ± SD) serum level Phenotypic variance explained by differences in age and BMI
Total Cholesterol mmol/l 6 . 1 1 ± 1.18 3 .0 %
Total Triglyceride mmol/l 1.51 ± 1.36 13%
LDL Cholesterol mmol/l 3 .9 9 ± 0 .9 3 3 .7 %
HDL Cholesterol mmol/l 1.42 ± 0 .3 4 13%
ApoB mg/100ml 108 .27 ± 18.9 4 .5 %
2.2.6 Swedish patients
The patient group consisted o f 143 male and female individuals from Stockholm county, Sweden, who had suffered a myocardial infarction below the age o f 45 years. Recruitment details, data on lipid, lipoprotein, apoprotein, and metabolic variables and descriptions o f DNA preparation for these individuals have been presented elsewhere (Hamsten et al. 1986b, 1987). ApoB genotyping has been described in Peacock et al. (1991). Individuals with serum cholesterol levels > 9.5m M , and/or triglyceride levels > 3.0m M , or with a diagnosis o f familial hypercholesterolaemia, diabetes or porphyria were excluded from
the lipid and lipoprotein analyses. Mean serum levels of certain lipid traits and apoB together with the amount of phenotypic variance explained by age, sex and BMI are given in Table 2.2.6.
Table 2.2.6 Mean serum lipid and lipoprotein traits and phenotypic variance explained bv age, sex and BMI in the Swedish patient group.
Mean ( ± SD) serum level Phenotypic variance explained by differences in age, sex and BMI
Total Cholesterol mmol/l 7 .1 7 ± 1.32 3 .8 %
Total Triglyceride mmol/l 2 .1 3 ± 1.70 4 .9 %
LDL Cholesterol mmol/l 4.81 ± 1.14 5 .7 %
HDL Cholesterol mmol/l 1.15 ± 1.26 2 5 %
ApoB mg/100ml 1 2 4 .8 ± 22 .3 6 .1 %
2.2.7 Chinese
A group o f 83 healthy Chinese males, mean age 36 years, living in Singapore. A detailed description o f this sample including apoB genotype data is presented in Saha et al. (1992a).
2.2.8 Afro-Carihheans
A group o f 47 healthy individuals aged 45 to 74 years (mean age 55 years), with at least three grandparents o f Afro-Caribbean origin, drawn from family practitioner registers in two North-West London health centres. This sample has been described in detail in Miller et al. (1989).
1.2.9 South Asians
A random subset o f 152 men drawn from a sample o f 1433 South Asian men aged 40-65, living in the west o f London, who have been investigated for CAD risk factors. The original sample was assembled from four factories and lists o f general practitioners in west London. 89% o f the men were Punjabi Sikhs and the rest were evenly divided between Gujarati and Punjabi Hindus. (McKeigue et al. 1991). ApoB genotyping is given in Renges et al. (1991).
2.2.10 St Thomas’ Atherosclerosis Regression Study (STARS)
A group o f 70 British patients, under 66 years o f age with CAD as determined by coronary angiography. Patients included in the study had untreated plasma cholesterol levels between 6.0 and lO.Ommol/1 and triglycerides below 4mmol/l. Patients who had suffered a myocardial infarction in the previous eight weeks, or who suffered from diabetes, hypertension, cardiac failure or malignancy were excluded from the study. After baseline assessment, patients were assigned into one o f three treatment groups: lipid-lowering diet alone, cholestyramine plus the lipid-lowering diet or no treatment and were followed for three years before repeat angiography (Watts et al. 1992). ApoB genotyping is given in Peacock et al. (199/p.
2.2.11 Camberlev
A group o f 364 Caucasian men attending a general practitioner’s surgery in Surrey, UK . All were aged between 50 and 61 years and had no clinical evidence o f CAD (Humphries et al. 1993).
2.2.12 ECTIM ^asbourg patients.
A group o f 211 men aged between 25 and 64 years, who had survived a myocardial infarction three to nine months prior to inclusion in the study. Their families had been resident in the Bas-Rhin department o f north-east France for the previous two generations and all four grandparents had been bom in Europe (Moreel et al. 1992).
2.2.13 ECTIM Strasbourg controls.
A group o f 194 men, age-matched with the patient group drawn from the Strasbourg electoral rolls (Moreel et al. 1992)