4.1.1. Study I

For study I, a total of 149 consecutive patients with serum cholesterol concentrations above 8 mmol/l referred to the Lipid Clinic of the Oulu University Central Hospital were examined. The presence of tendon xanthomata, a family history of high cholesterol levels, and heart disease or sudden deaths in the first-degree relatives were recorded. The clinical work was completed before the result of the DNA analysis was obtained. Thirty-nine patients with type IV or V hyperlipidemia (fasting plasma triglycerides >4.0 mmol/l) or secondary hyperlipidemia were excluded. The diagnosis of FH was based on the following criteria: serum total cholesterol above 8 mmol/l, LDL cholesterol above the 90th percentile, and tendon xanthomata in the patient or one first-degree relative. The plasma lipids of the study subjects are shown in Table 4-1.

4.1.2. Study II

Forty-nine non-FH patients, 20 women and 29 men, were recruited from the Oulu University Lipid Clinic for study II. All patients were ambulatory throughout the study and they received information on a low-fat, low-cholesterol diet before the study. The patients discontinued their hypocholesterolemic drugs at least two weeks before the study. The patients received 1.0 g of KI daily by mouth in divided doses for 3 days before and throughout the study to inhibit the uptake of radio iodine by the thyroid.

The homologous LDL was obtained from two healthy male volunteers, in whom diseases transmitted through blood transfusion had been excluded. The total cholesterol of donor 1 was 4.62 mmol/l, triglycerides 0.75 mmol/l, and fractional catabolic rate (FCR) for autologous LDL 0.32 pools/day while the values of donor 2 were 4.51 mmol/l, 0.94 mmol/l and 0.37 pools/day, respectively. The FCR of donor 1"s LDL in donor 2 was 0.33 pools/day.

4.1.3. Study III

The patients included in study III had been consecutively referred to one ward of the Oulu University Hospital Department of Medicine for selective coronary angiography because of chest pain or suspected coronary artery disease. The plasma lipid profile and apolipoprotein E phenotype were not determined in 28 patients. In addition, four patients on lipid-lowering therapy were excluded from the study. 122 patients, 95 males and 27 females, with all the data was available were included in the study.

The control group comprised clients of the State Occupational Health Service Station in Oulu, who had volunteered for a survey of lipid values and maximal exercise electrocardiography. Five of the controls were taking beta-blocking agents for hypertension, and this treatment was stopped two days before the examination. The exercise electrocardiography revealed three controls with ST-depressions of more than 1 mm that were planar or down-sloping and persisted for 0.08 seconds after the J point. Their coronary angiographies were normal, and they were included in the control group. The demographic characteristics and medication schedules of the male and female controls and patients with different extensions of coronary artery disease are shown in the Table 4-2 and Table 4-3.

4.1.4. Study IV

Patients of either sex between the ages of 18 and 63 were screened for study IV in four locations in Northern Finland. The inclusion criterion for lovastatin treatment was a total plasma cholesterol >5 mmol/l during an adequate diet and colestipol treatment. 203 patients were screened for the study and 150 patients started the lovastatin treatment. Ten patients were taking colestipol less than 20 g/day due to obstipation or abdominal discomfort, one patient had a cholesterol value lower than 5 mmol/l with lovastatin 20 mg daily, one patient had headache with lovastatin 20 mg/day, one patient had slightly elevated creatine kinase with lovastatin 20 mg/day, and one patient discontinued the study during the lovastatin treatment. The flowchart of study IV is shown in Figure 4-1, and the demographic characteristics of the patients are given in Table 4-4. Familial hypercholesterolemia was defined as plasma cholesterol > 8 mmol/l with tendon xanthomata or a family history of severe hypercholesterolemia and/or coronary artery disease at an early age. Thirty-six patients had the CETP activity measured, half of them were males and half females, 26 had polygenic hypercholesterolemia and ten had FH. Ten patients had undergone coronary artery bypass grafting (CABG) or AMI, seven had the clinical diagnosis of angina pectoris, and 19 had no clinical sign of coronary artery disease.

4.1.5. Study V

Altogether 209 patients were screened for study V by local occupational health services. Twenty-five patients were taking concomitant medications during the active treatment phase: ten b-blocking agents, nine diuretics, seven calcium antagonists, four aspirin, nine nitrates and three angiotensin convertase inhibitors in different combi­nations with a stable regimen during the whole study. Demographic data on the patients and controls participating in the active treatment phase are shown in Table 4-5 and the flowchart in Figure 4-2. Only patients with adequate compliance were included in the efficacy analyses. When assessing the influence of the apo B and apo E polymorphisms on drug efficacy and the effect of RS-86505-007 on Lp(a) concentrations, all patients receiving the active drug 6 mg tid for whom DNA was available were included.