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Objectives: To evaluate the optimal lipid to measure in monitoring patients, we assessed three factors that influence the choice of monitoring tests: (1) clinical validity; (2) responsiveness to therapy changes and (3) the size of the long-term 'signal-to-noise' ratio., Design: Longitudinal analyses of repeated lipid measurement over 5 years., Setting: Subsidiary analysis of a Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study-a clinical trial in Australia, New Zealand and Finland., Participants: 9014 patients aged 31-75 years with previous acute coronary syndromes., Interventions: Patients were randomly assigned to 40 mg daily pravastatin or placebo., Primary and Secondary Outcome Measures: We used data on serial lipid measurements-at randomisation, 6 months and 12 months, and then annually to 5 years-of total cholesterol; low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and their ratios; triglycerides; and apolipoproteins A and B and their ratio and their ability to predict coronary events., Results: All the lipid measures were statistically significantly associated with future coronary events, but the associations between each of the three ratio measures (total or LDL cholesterol to HDL cholesterol, and apolipoprotein B to apolipoprotein A1) and the time to a coronary event were better than those for any of the single lipid measures. The two cholesterol ratios also ranked highly for the long-term signal-to-noise ratios. However, LDL cholesterol and non-HDL cholesterol showed the most responsiveness to treatment change., Conclusions: Lipid monitoring is increasingly common, but current guidelines vary. No single measure was best on all three criteria. Total cholesterol did not rank highly on any single criterion. However, measurements based on cholesterol subfractions-non-HDL cholesterol (total cholesterol minus HDL cholesterol) and the two ratios-appeared superior to total cholesterol or any of the apolipoprotein options. Guidelines should consider using non-HDL cholesterol or a ratio measure for initial treatment decisions and subsequent monitoring.

Objective: Association between lipoprotein(a) (Lp(a)) level and a first-ever coronary (CHD) event is recognized. Less is evident in patients with overt CHD and stable symptoms in whom we investigated associations between Lp(a) and future events., Approach and Results: Relationships between Lp(a) concentration and CHD and cardiovascular disease outcomes during 6 years' median follow-up were evaluated in the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study. Lp(a) concentrations were measured in plasma from 7863 patients who had sustained a previous coronary event and been randomized to pravastatin or placebo. Lp(a) levels were categorized by lowest half, third quartile, 75th to 90th percentile, and highest decile. The prognostic value of Lp(a) on outcomes was assessed by fitting a Cox proportional-hazards model after adjustment for other risk factors and baseline cardiovascular disorders. The prognostic value of a change in Lp(a) at year 1 categorized by quartiles was assessed using Cox regression in a landmark model incorporating the above factors and baseline levels. Baseline Lp(a) concentration was associated with total CHD events (P<0.001), total cardiovascular disease events (P=0.002), and coronary events (P=0.03). Greatest risk occurred at >73 mg/dL, upper decile. For events after year 1, an increase in Lp(a) at 1 year was associated with adverse outcomes for total CHD events and total cardiovascular disease events (P=0.002 each)., Conclusions: In the LIPID study, baseline Lp(a) was associated with future cardiovascular disease and CHD events. Increased Lp(a) concentrations after 1 year were also associated with future events, supporting measurement of Lp(a) for risk assessment of patients with known CHD.

Background: Cardiovascular mortality is higher in New Zealand compared to Australia, but reasons for this difference are uncertain. This study describes differences in cardiovascular risk factors and cardiovascular mortality in Australians and New Zealanders with stable coronary artery disease stratified by socioeconomic status., Methods: Socioeconomic status was estimated from the residential area of 5949 Australians and 2784 New Zealanders with a history of myocardial infarction or unstable angina who participated in the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study. Socioeconomic and international differences in cardiovascular risk factors, medical treatments, and cardiovascular mortality during a median follow-up period of 7.8 years were evaluated., Results: Cardiovascular mortality increased as the median residential-area income decreased in both Australia (hazard ratio [HR]/income tertile 1.20, 95% confidence interval [CI] 1.08-1.32) and New Zealand (HR 1.16, 95%CI 1.02-1.31), but was higher in New Zealand across all socioeconomic groups (HR 1.42, 95%CI 1.25-1.61). Obesity, smoking, and a high white blood cell count at baseline were associated with higher cardiovascular mortality and were more common in lower-income areas in both countries. The total:HDL cholesterol ratio was higher in New Zealand, but similar across all socioeconomic groups. In both countries there were socioeconomic gradients in open-label usage of cholesterol-lowering medication, percutaneous coronary intervention, and coronary artery bypass surgery. However, Australians in all socioeconomic groups were more likely than New Zealanders to receive these treatments., Conclusions: Although there is an important socioeconomic gradient in cardiovascular mortality in both Australia and New Zealand, cardiovascular mortality is higher in New Zealanders than Australians with stable coronary disease from all socioeconomic groups.

Background: Comparisons of the relation of diet with coronary heart disease (CHD) between countries with similar socioeconomic environments have been few. Patients in Australia and New Zealand (n = 9014) who participated in a large secondary prevention trial had significantly different CHD mortality rates., Objective: The objective of this study was to ascertain the effects of nutrient consumption on cardiovascular disease risk in patients from the 2 countries., Design: Nutrient consumption patterns were surveyed in a subgroup of 1077 patients on 3 occasions over 4 y during an intervention trial with a statin., Results: Within the entire cohort of 9014 patients, the New Zealanders had significantly (40%) more cardiovascular deaths than did the Australians. In the subgroup of 1077 patients, the New Zealanders were found at entry to have eaten significantly more total (69.34 +/- 12.35 compared with 66.45 +/- 12.9 g/d) and saturated (26.23 +/- 8.41 compared with 24.37 +/- 7.36 g/d) fat (P < 0.001 for each) and to have significantly (4%) higher concentrations of LDL cholesterol (3.96 +/- 0.74 compared with 3.8 +/- 0.76 mmol/L; P < 0.001) than did the Australians. At baseline, patients with previous coronary artery bypass grafting had diets that were significantly different from those of patients without previous coronary artery bypass grafting. Relations between nutrients and plasma lipids confirmed the direct effects of saturated fatty acids on LDL cholesterol and of alcohol on plasma triacylglycerol and HDL cholesterol. Dietary counseling throughout the trial led to significant improvements in compliance with guidelines. However, neither the baseline nor the improved 1-y nutrient intakes predicted future changes in cardiovascular events., Conclusion: Differences in CHD mortality and in LDL-cholesterol concentrations between 2 populations with similar socioeconomic and cultural backgrounds were consistent with the amounts and types of fats eaten.

Background: Depression after myocardial infarction has been associated with increased cardiovascular mortality. This study assessed whether depressive symptoms were associated with adverse outcomes in people with a history of an acute coronary syndrome, and evaluated possible explanations for such an association., Methods and Results: Depressive symptoms were assessed using the General Health Questionnaire at least 5 months after hospital admission for acute myocardial infarction or unstable angina in 1130 participants of the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study, a multicentre, placebo-controlled, clinical trial of cholesterol-lowering treatment. Cardiovascular symptoms, self-rated general health, cardiovascular risk factors, employment status, social support and life events were also assessed at the baseline visit. Cardiovascular death (n=114), non-fatal myocardial infarction (n=108), non-fatal stroke (n=53) and unstable angina (n=274) were documented during a median follow-up period of 8.1 years. Individuals with depressive symptoms (General Health Questionnaire score >/=5; 22% of participants) were more likely to report angina, dyspnoea, claudication, poorer general health, not being in paid employment, few social contacts and/or adverse life events (P<0.05 for all). There was a modest association between depressive symptoms and cardiovascular events (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.13-1.77), but not cardiovascular death (HR 1.12. 95% CI 0.71-1.77). After adjustment for symptoms related to cardiovascular disease, the HR for cardiovascular events was 1.22 (95% CI 0.97-1.53). After further adjustment for employment status, social support and life events, the HR was 1.13 (95% confidence interval 0.87-1.47)., Conclusions: There was no significant association between depressive symptoms and fatal or non-fatal cardiovascular events after adjustment for cardiovascular symptoms associated with poorer prognosis. Previously observed associations between depression and cardiovascular mortality may not be causal.

Objective: To measure the cost-effectiveness of cholesterol-lowering therapy with pravastatin in patients with established ischaemic heart disease and average baseline cholesterol levels., Design: Prospective economic evaluation within a double-blind randomised trial (Long-Term Intervention with Pravastatin in Ischaemic Disease [LIPID]), in which patients with a history of unstable angina or previous myocardial infarction were randomised to receive 40 mg of pravastatin daily or matching placebo., Patients and Setting: 9014 patients aged 35-75 years from 85 centres in Australia and New Zealand, recruited from June 1990 to December 1992., Main Outcome Measures: Cost per death averted, cost per life-year gained, and cost per quality-adjusted life-year gained, calculated from measures of hospitalisations, medication use, outpatient visits, and quality of life., Results: The LIPID trial showed a 22% relative reduction in all-cause mortality (P < 0.001). Over a mean follow-up of 6 years, hospital admissions for coronary heart disease and coronary revascularisation were reduced by about 20%. Over this period, pravastatin cost $A4913 per patient, but reduced total hospitalisation costs by $A1385 per patient and other long-term medication costs by $A360 per patient. In a subsample of patients, average quality of life was 0.98 (where 0 = dead and 1 = normal good health); the treatment groups were not significantly different. The absolute reduction in all-cause mortality was 3.0% (95% CI, 1.6%-4.4%), and the incremental cost was $3246 per patient, resulting in a cost per life saved of $107 730 (95% CI, $68 626-$209 881) within the study period. Extrapolating long-term survival from the placebo group, the undiscounted cost per life-year saved was $7695 (and $10 938 with costs and life-years discounted at an annual rate of 5%)., Conclusions: Pravastatin therapy for patients with a history of myocardial infarction or unstable angina and average cholesterol levels reduces all-cause mortality and appears cost effective compared with accepted treatments in high-income countries.

Background: In two large secondary prevention trials of pravastatin, risk reduction was not significant in participants who had low baseline LDL-C concentrations (that is, <125 mg/dL). We conducted exploratory analyses of participant characteristics, lipid risk factors, and risk reduction in this group., Methods and Results: Among 13 173 participants with coronary heart disease (CHD), 2607 had baseline LDL-C <125 mg/dL. Those with LDL-C <125 compared with > or =125 mg/dL were more likely to be diabetic (15% versus 9%), hypertensive (46 versus 41%), and male (89% versus 83%); they had higher triglycerides (169 versus 154 mg/dL), lower HDL-C (36.5 versus 38 mg/dL), and similar body mass index (27 kg/m2); and pravastatin lowered their LDL-C by 36 mg/dL (32%) versus 45 mg/dL (29%). During 5.8-year (mean) follow-up, HDL-C and triglycerides were both significantly stronger predictors of recurrent CHD events in participants with LDL-C <125 than > or =125 mg/dL. In diabetic participants with low LDL-C, pravastatin decreased CHD events from 34% to 22% (relative risk, 0.56; 95% CI, 0.37 to 0.83; P=0.004), significantly different from the effect in nondiabetic participants with low LDL-C (P interaction, 0.005) (event rate, 21%; relative risk, 1.06 [95% CI, 0.89 to 1.27]). There were trends toward risk reduction in smokers and in those with low HDL-C, <40 mg/dL., Conclusions: Among patients with CHD who have low LDL-C, diabetics have much higher subsequent CHD event rates than do nondiabetics. Pravastatin reduced the event rate in diabetics to that of nondiabetic participants. The results also suggest enhanced therapeutic potential for improving HDL-C and triglycerides in patients with CHD who have low LDL-C concentrations.

The Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) study was designed when considerable disagreement existed as to relative benefits and risks of cholesterol reduction. Between June 1990 and December 1992, 9,014 patients aged 31-75 years were randomized to receive either pravastatin 40 mg once daily or placebo. These patients had experienced either acute myocardial infarction or unstable angina within the preceding 3 months to 3 years and had total cholesterol levels of 155-271 mg/dl (4.0-7.0 mmol/liter). All patients received dietary advice. The LIPID study is projected for conclusion in 1997, after a follow-up period of at least 5 years. The primary study endpoint is mortality due to coronary artery disease (CAD). The Scandinavian Simvastatin Survival Study (4S) is the first secondary prevention trial to show a reduction in total mortality with lipid-lowering therapy. However, the LIPID study should continue for the following reasons: (1) important differences exist between the LIPID study and 4S cohorts. Overall, > 80% of the LIPID patients could not have been included in 4S on the basis of their cholesterol level, age, or history of CAD; (2) the LIPID study will also provide important information on noncoronary mortality and on other groups, such as women and diabetic patients, who have been underrepresented in previous trials; (3) the LIPID study design allows for clinical management, including lipid-lowering therapy, to be at the discretion of the physician managing a trial patient. The 4S results have been brought to the attention of all LIPID investigators, Institutional Ethics Committees, the physicians of the individual patients, and the patients themselves.(ABSTRACT TRUNCATED AT 250 WORDS)