Ingmar Jungner

High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study

BACKGROUND Apolipoprotein B (apoB) and apolipoprotein A-I (apoA-I) are thought to be better predictors of acute myocardial infarction than total cholesterol and LDL-cholesterol. We investigated whether apoB and apoA-I are predictors of risk of fatal myocardial infarction. We also aimed to establish whether apoB and apoA-I add further information about risk of fatal myocardial infarction to that obtained with total cholesterol, triglycerides, and LDL-cholesterol. METHODS We recruited 175553 individuals mainly from screening programmes. We measured concentrations of apoB, apoA-I, total cholesterol, and triglycerides, and calculated apoB/apoA-I ratio and concentrations of LDL-cholesterol and HDL-cholesterol. The relation between death from acute myocardial infarction and initial values for apoB, apoA-I, and the other lipids was examined. FINDINGS Mean follow-up was 66.8 months (SD 41.3) for 98722 men and 64.4 months (41.4) for 76831 women. 864 men and 359 women had fatal myocardial infarction. In univariate analyses adjusted for age and in multivariate analyses adjusted for age, total cholesterol, and triglycerides, the values for apoB and apoB/apoA-I ratio were strongly and positively related to increased risk of fatal myocardial infarction in men and in women. ApoA-I was noted to be protective. In multivariate analysis, apoB was a stronger predictor of risk than LDL-cholesterol in both sexes. INTERPRETATION Although LDL-cholesterol and HDL-cholesterol are known risk factors, we suggest that apoB, apoB/apoA-I, and apoA-I should also be regarded as highly predictive in evaluation of cardiac risk. Although increased throughout the range of values of LDL-cholesterol, apoB and apoA-I might be of greatest value in diagnosis and treatment in men and women who have common lipid abnormalities, but have normal or low concentrations of LDL-cholesterol.

Apolipoproteins versus lipids as indices of coronary risk and as targets for statin treatment

More Nobel prizes have been awarded for the study of cholesterol than for any other molecule. Presently, concentration of LDL cholesterol is the fundamental index of risk of vascular disease. It is an estimate of the mass of cholesterol in the LDL fraction in plasma. By contrast, the value for apolipoprotein B is a measurement of the total number of atherogenic particles. Results of many studies show that apolipoprotein B is a better marker of risk of vascular disease and a better guide to the adequacy of statin treatment than any cholesterol index. Moreover, the ratio of apolipoprotein B/apolipoprotein A-1 seems superior to the ratio of total cholesterol/HDL cholesterol as an overall index of the risk of vascular disease. We review this evidence and include observations that were not previously published. The pathophysiological bases for the superiority of apolipoprotein B to cholesterol as a predictor of risk are reported elsewhere. 1

The apoB/apoA-I ratio: a strong, new risk factor for cardiovascular disease and a target for lipid-lowering therapy--a review of the evidence.

During the last several years interest has focused on the importance of the lipid‐transporting apolipoproteins – apoB transports all potentially atherogenic very low‐density lipoprotein (VLDL), intermediate‐density lipoprotein (IDL) and LDL particles, and apoA‐I transports and acts as the major antiatherogenic protein in the HDL particles. The evidence for the apoB/apoA‐I ratio being a strong, new risk factor for cardiovascular (CV) disease and a target for lipid‐lowering therapy is reviewed. Results from clinical prospective studies and lipid‐lowering trials in healthy subjects and in patients with different clinical manifestations of atherosclerosis are reported. Risk of nonfatal and fatal myocardial infarction and stroke, and manifestations of atherosclerosis documented by angiographic, ultrasound and other techniques has been related to conventional lipids and apolipoproteins (apo). The cholesterol balance determined as the apoB/apoA‐I ratio has repeatedly been shown to be a better marker than lipids, lipoproteins and lipid ratios. The results indicate that the apoB/apoA‐I ratio is a simple, accurate and new risk factor for CV disease – the lower the apoB/apoA‐I ratio, the lower is the risk. Guidelines should be developed in order to recognize the important clinical risk information embedded in the apoB/apoA‐I ratio.

Apolipoprotein B and apolipoprotein A-I: risk indicators of coronary heart disease and targets for lipid-modifying therapy

Although LDL cholesterol (LDL‐C) is associated with an increased risk of coronary heart disease, other lipoproteins and their constituents, apolipoproteins, may play an important role in atherosclerosis. Elevated levels of apolipoprotein (apo) B, a constituent of atherogenic lipoproteins, and reduced levels of apo A‐I, a component of anti‐atherogenic HDL, are associated with increased cardiac events. Apo B, apo A‐I and the apo B/apo A‐I ratio have been reported as better predictors of cardiovascular events than LDL‐C and they even retain their predictive power in patients receiving lipid‐modifying therapy. Measurement of these apolipoproteins could improve cardiovascular risk prediction.

The apoB/apoA-I ratio is better than the cholesterol ratios to estimate the balance between plasma proatherogenic and antiatherogenic lipoproteins and to predict coronary risk

Abstract Background: The apolipoprotein B (apoB)/apoA-I ratio represents the balance of proatherogenic and antiatherogenic lipoproteins. The purpose of this study was to determine whether the apoB/apoA-I ratio was superior to any of the cholesterol ratios – total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C), low-density lipoprotein cholesterol (LDL-C)/HDL-C and non-HDL-C/HDL-C – in predicting the risk of coronary disease. Moreover, we examined whether any lipids, lipoproteins or cholesterol ratios add significant predictive information beyond that provided by the apoB/apoA-I ratio. Methods: Plasma lipids, lipoproteins, apoB, and apoA-I were measured in 69,030 men and 57,168 women above 40years of age. After a mean follow-up of 98months, 1183 men and 560 women had died from a myocardial infarction in this prospective apolipoprotein-related mortality risk (AMORIS) study. Results: High apoB and a high apoB/apoA-I ratio were strongly related to increased coronary risk, while high apoA-I was inversely related to risk. The apoB/apoA-I ratio was superior to any of the cholesterol ratios in predicting risk. This advantage was most pronounced in subjects with LDL-C levels <3.6mmol/l. Addition of lipids, lipoproteins or any cholesterol ratio to apoB/apoA-I in risk models did not further improve the strong predictive value of apoB/apoA-I. Conclusions: These results indicate that the apoB/apoA-I ratio is at present the best single lipoprotein-related variable to quantitate coronary risk. Given the additional advantages apolipoproteins possess – fasting samples are not required, apoB/apoA-I is a better index of the adequacy of statin therapy than LDL-C, and the measurement of apoB and apoA-I are standardized, whereas LDL-C and HDL-C are not – there would appear to be considerable advantage to integrating apolipoproteins into clinical practice.

Uric acid and risk of myocardial infarction, stroke and congestive heart failure in 417 734 men and women in the Apolipoprotein MOrtality RISk study (AMORIS)

Objectives.  Few studies have simultaneously analysed the influence of elevated serum uric acid (UA) on acute myocardial infarction (AMI), ischaemic and haemorrhagic stroke (IS, HS) and congestive heart failure (CHF) in large healthy populations. We, here, examine UA as a risk factor for AMI, stroke and CHF by age and gender in the Apolipoprotein MOrtality RISk (AMORIS) Study.

Lipids, myocardial infarction and ischaemic stroke in patients with rheumatoid arthritis in the Apolipoprotein-related Mortality RISk (AMORIS) Study

Objectives To examine the rates of acute myocardial infarction (AMI) and ischaemic stroke (IS) and to examine the predictive value of total cholesterol (TC) and triglycerides (TG) for AMI and IS in patients with rheumatoid arthritis (RA) and people without RA. Methods In the Apolipoprotein MOrtality RISk (AMORIS) Study 480 406 people (including 1779 with RA, of whom 214 had an AMI and 165 an IS) were followed for 11.8 (range 7–17) years. Cox regression analysis was used to calculate HR per SD increase in TC or TG with 95% CI. All values were adjusted for age, diabetes and hypertension. Results The levels of TC and TG were significantly lower in patients with RA than in people without RA. Despite this, the rate of AMI and IS per 1000 years was at least 1.6 times higher in RA than non-RA. TC was nearly significantly predictive for AMI (HR/SD 1.13 (95% CI 0.99 to 1.29), p=0.07) and significantly predictive for future IS in RA (HR/SD 1.20 (95% CI 1.03 to 1.40), p=0.02). TG had no relationship to development of AMI (1.07, 0.94 to 1.21, p=0.29), but was weakly related to IS (1.13, 0.99 to 1.27, p=0.06). In contrast, both TC and TG were significant predictors of AMI and IS in people without RA. Conclusions Patients with RA had 1.6 times higher rate of AMI and IS than people without RA. TC and TG were significant predictors of AMI and IS in people without RA, whereas the predictive value in RA was not consistent.

Stroke mortality and the apoB/apoA‐I ratio: results of the AMORIS prospective study

Objectives.  LDL cholesterol is a well‐established risk factor for myocardial infarction, but not for stroke. The main objective of the present study was to determine if the risk of stroke is related to the balance between the proatherogenic apoB lipoprotein particles and the antiatherogenic apoA‐I particles as is the case for myocardial infarction.

Apolipoprotein B and A-I in relation to serum cholesterol and triglycerides in 43,000 Swedish males and females.

SummaryAutomated methods for the determination of apolipoprotein B and apolipoprotein A-I were developed, tested, and applied in screening programs of large populations to improve information about the composition and degree of hyperlipoproteinemia. Apolipoproteins B and A-I, total cholesterol, and triglyceride levels were measured in 25659 males and 18 144 females between 20 and 79 years of age, the majority subjectively healthy. The immunoturbidimetric methods used for apolipoproteins B and A-I were shown to be stable over time, and the errors of the methods were below 7%. Apolipoprotein B correlated with total cholesterol (r=0.86,P<0.001) for each age decile group and for both sexes (r=0.82–0.87,P<0.001). For a subsample comparable to the large population, apolipoprotein B correlated with cholesterol in low density (i.e., the atherogenic particle),r=0.89,P<0.001. The mean values for apolipoprotein B increased with age for both sexes, with much higher levels in males than in females under 50 years of age. Apolipoprotein A-I was lower in males than in females in all age-groups. At all cholesterol levels males had higher apolipoprotein B, and at the same triglyceride level, also lower apolipoprotein A-I and hence a higher B/A-I ratio than females. Using apolipoprotein B and A-I (high-density lipoprotein cholesterol) particles and adopting Swedish consensus criteria for the diagnosis of risk of iisk of ischemic heart disease, examples are given showing that many individuals, especially females, with high or borderline total serum cholesterol can be excluded from further investigation/treatment for hypercholesterolemia. In the age-group 40–49 years, a total cholesterol value of 6.5 mmol/l was found to correspond to an apolipoprotein B value of 1.39 g/l for males and to 1.32 g/l for females. Whereas 30% of males and 18% of females had total cholesterol values greater than or equal to 6.5 mmol/l, 19.7% of males and 7.5% of females had apolipoprotein B levels above 1.5 g/l (this cut-off point corresponds to a low-density lipoprotein cholesterol value of 5.0 mmol/l). It is suggested that the determination of apolipoprotein B and A-I levels be used to back up screening and facilitate the diagnosis of atherogenic and treatable high serum lipids.

Prostate cancer risk in the Swedish AMORIS study : the interplay among triglycerides, total cholesterol, and glucose

In a cohort including 5112 prostate cancer (pCa) patients, the authors investigated associations among triglycerides (TG), total cholesterol (TC), and pCa while taking into account glucose.