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Aim: To evaluate dyslipidemia as predictor of myocardial infarction (MI) in subjects with or without chronic kidney disease (CKD)., Methods: In 142,394 middle-aged Swedes referred for laboratory evaluation, glomerular filtration rates (GFR) were estimated using the Modification of Diet in Renal Disease study equation. CKD was defined as GFR 15-60 mL/min/1.73 m(2). Subjects were stratified into presence or absence of CKD, and lipid measures were related to MI using Cox's proportional hazards regression., Results: During 12 years of follow-up there were 5,466 MIs. The adjusted hazard ratio for MI for the highest versus the lowest quartile of the apolipoprotein (apo) B/apoA-1 ratio among individuals without CKD was 2.88 (95% confidence interval 2.54-3.26) and for those with CKD 3.35 (2.25-4.91). The corresponding estimates for the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio were 3.13 (2.78-3.52) and 3.54 (2.43-5.17), respectively. Receiver operator characteristics analyses showed an advantage in the prediction of MI for the apoB/apoA-1 ratio as compared to conventional lipids (P < 0.0001)., Conclusions: The ratio of apoB/apoA-1, the ratio of total cholesterol/HDL cholesterol, and non-HDL cholesterol were all strong predictors of myocardial infarction, both among subjects with and without renal dysfunction, with a possible advantage for the apoB/apoA-1 ratio.

Aims: Few studies have analysed the influence of lipoprotein components (LC) on the development of congestive heart failure (HF) in large healthy populations. We examined LC together with glucose, haptoglobin (Hp), and uric acid (UA) as risk factors for HF in the Apolipoprotein MOrtality RISk (AMORIS) study. We also explored the possible interaction between these factors and the apolipoprotein B to apolipoprotein A-1 ratio (apoB/apoA-1) in HF., Methods and Results: This was a prospective study of HF conducted over 11.8 years through links with the Swedish hospital discharge and mortality registers. Lipoprotein components and other risk factors were measured in 84 740 men and women during health check-ups. All LC were strongly associated with HF per gender adjusted for risk factors. Relationships were stronger for men than for women. Among LC the apoB/apoA-1 ratio was the strongest risk factor for HF in men and triglycerides (TG) in women, but differences in strength were not large. The Hp and UA added predictive information to that of the apoB/apoA-1 ratio, but glucose did not. There was no detectable interaction (synergistic effects) on relative risk between apoB/apoA-1 and these three additional factors., Conclusion: Over and above adjustment factors, the apoB/apoA-1 ratio and TG were the most predictive of the LC, but all LC were highly significantly related to the development of HF.

Background: Few studies have analysed the importance of haptoglobin (Hp) as a risk factor for acute myocardial infarction (AMI), stroke, and heart failure (HF) in large healthy populations., Aims: We examined Hp as risk factor for AMI, stroke, and HF in the Apolipoprotein MOrtality RISk (AMORIS) Study and compared its predictive strength with that of total serum cholesterol (TC)., Methods: Prospective study (11.8 years) of AMI, stroke, and HF through linkage with Swedish hospital discharge and mortality registers with measurements of Hp in 342,125 subjects., Results: Hp is a significant risk factor of AMI, stroke, and HF. Relationships were stronger for men than women with regard to stroke and HF, but not AMI. Hp was almost as predictive as TC for AMI and about equally predictive of stroke with a stronger relationship to ischaemic than haemorrhagic stroke. A 4.2-fold increase in risk of AMI was observed comparing subjects in the joint lower quartiles of TC and Hp to those in the upper. For stroke, the risk increase was 2-fold, and 1.5-fold for HF., Interpretation: The inflammation marker Hp carried as much additional predictive information value on AMI and stroke as TC. Hp was also a risk factor of HF.

Age is by far the most powerful risk factor for cardiovascular disease. Moreover, the consequences of age are considered inevitable and irreversible. In this study, we examined whether age is, to a major degree, a modifiable risk factor. In the subjects in the Apolipoprotein-related Mortality Risk (AMORIS) study, we show that fatal myocardial infarction (MI) is uncommon in men before the sixth decade and in women before the seventh. In age-adjusted analyses, the risk of fatal MI increase successively with each decile of the apolipoprotein (apo) B/apoA-I ratio, confirming the importance of the balance of the atherogenic and antiatherogenic lipoproteins as a fundamental determinant of the likelihood of clinical events. We then determined the risk of fatal acute MI over time in the highest decile of the apoB/apoA-I ratio compared with the lowest decile. For the purposes of this analysis, we assume that all events in the lowest decile of the apoB/apoA-I ratio represent the nonmodifiable adverse effects of age. This assumption maximizes the irreversible effects of age. Because the change in age is identical for the subjects in both deciles, the difference in risk between the lowest and highest deciles of the apoB/apoA-I ratio represents the consequence of exposure over time to very high values of this ratio. Exposure is the modifiable element of risk, and it contributed to most of the risk. In conclusion, it appears that not all of the effects of age are irreversible. therefore, outcomes with early prevention might be much more favorable than usually assumed.

Purpose of Review: To compare the potential of high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I, the major protein in HDL particles, in predicting cardiovascular risk. Pros and cons for using these risk markers are discussed., Recent Findings: Both HDL cholesterol and apoA-I are in most clinical conditions antiatherogenic - the higher the values, the lower the cardiovascular risk. Methodological and physiological factors speak in favour of using apoA-I rather than HDL cholesterol as a marker of risk. In prospective risk studies and in lipid-lowering trials it has been shown that the apoB/A-I ratio, which reflects the cholesterol balance between all potentially atherogenic (apoB) and antiatherogenic lipoproteins (apoA-I), is a better risk marker than low-density lipoprotein cholesterol, HDL cholesterol and lipid ratios in predicting cardiovascular risk and response to lipid lowering induced by statins. Practical advantages speak in favour of using apoB and apoA-I - fasting is not needed to analyze and interpret the values of apoB and apoA-I., Summary: New guidelines should be developed in which target values for apoB and apoA-I are defined to enable the use of these new strong risk markers/factors in clinical practice.

The lipoprotein-related risk of coronary artery disease is determined principally by the balance between atherogenic lipoprotein particles, i.e., the lipoprotein that contain apolipoprotein-B (apo-B), and the antiatherogenic particles, i.e., high-density lipoprotein particles that contain apo-A-I. However, there is also considerable evidence that patients with predominantly small dense low-density lipoprotein (LDL) have more adverse clinical outcomes than do those with large buoyant LDL. The AMORIS study prospectively examined the relative importance of lipoprotein lipids versus apolipoproteins on the risk of fatal myocardial infarction in a large Swedish cohort. This updated analysis includes 69,029 men and 57,167 women who were followed for a mean of 10.3 years. Our objective was to determine whether LDL size as reflected by the LDL cholesterol/apo-B ratio added significant predictive power to apo-B or the apo-B/apo-A-I ratio. Although apo-A-I added significantly to the predictive power of apo-B, categorical and continuous multivariate analyses showed that this is not the case for LDL size. The strongest single lipoprotein-related risk factor was the apo-B/apo-A-I ratio. In conclusion, these results provide further confirmation of the importance of determining apo-B and apo-A-I in routine clinical practice.

In order to make an appropriate evaluation of cardiac risk related to lipids for a given individual, measurements of the "bad" LDL and the "good" HDL should be performed. Often a value of total cholesterol can be misleading. Cholesterol and triglycerides in the blood are bound to and transported by apolipoproteins (apo). ApoB only occurs in the atherogenic lipoproteins, mainly in LDL, whereas apoA-I is bound only to HDL. We review prospective epidemiological trials and clinical trials in which statins have been used to reduce cardiac risk. The results indicate that apoB, apoA-I, and especially the balance of apoB/apoA-I, are more closely related to cardiac risk and to clinical outcome than LDL or HDL. Methodological advantages speak in favour of measuring apoB and apoA-I in clinical practice.

Background: The long-term trajectories of lipid and glucose levels in subjects who experience a major cardiovascular (CV) event at a young age has not been well studied. Our objective was to investigate lipid, lipoprotein, apolipoprotein (apo), and glucose levels in individuals experiencing a CV event before 50 years of age. Methods and findings: A first CV event [non-fatal myocardial infarction (MI), coronary revascularisation, or CV related death] before age 50 was recorded in 2,939 (cumulative incidence 1.2% in males and 0.3% in females) of 361,353 individuals included in the prospective Swedish AMORIS (Apolipoprotein-related MOrtality RISk) study with health examinations 1985–1996 and follow-up through 2011. In a nested case-control analysis, cases with a CV event were matched to randomly selected controls. Population risk factor trajectories were calculated up to 20 years prior to an event. Total cholesterol (TC), triglyceride (TG), and glucose levels were higher in cases than in controls as early as 20 years prior to the event with differences increasing over time. Low density lipoprotein, apoB, and the apoB/apoA-1 ratio were higher and increased over time, while HDL and apoA-1 were lower in cases compared to controls. The odds ratio was 2.5 (95% confidence interval 1.6–3.7) for TC ≥5 mmol/L and TG ≥1.7 mmol/L in cases versus controls. The adjusted population-attributable fractions including lipids, glucose, diabetes, smoking, hypertension, and obesity indicated that about 50% of CV events before age 50 may be associated with elevated lipid and glucose levels. Conclusions: Elevated TC, TG, LDL, apoB, and glucose levels and high apoB/apo A-1 ratio documented two decades before a CV event in subjects younger than 50 years may account for about half of CV events before age 50, which calls for early recognition and possibly treatment of modifiable CV risk factors in young individuals. [ABSTRACT FROM AUTHOR]

Background. Few studies have tested differences in relationships between hemoglobin (Hb) and long-term risk of major cardiovascular diseases according to age and gender in healthy subjects as opposed to anemia. Aims. Such relationships were examined and risk-tested in relation to Hb values in the Apolipoprotein MOrtality RISk (AMORIS) Study. Methods. Using data from AMORIS and the Swedish hospital discharge and mortality registers, a prospective cohort study of 114,159 subjects with mean follow-up of 11.8 years, the association between Hb and risk of acute myocardial infarction (AMI), ischemic stroke (IS), and congestive heart failure (CHF) by Cox regression analysis according to age and gender was studied. Results. Elevated Hb levels were associated to acute myocardial infarction (AMI) (HR 1.10 (1.06-1.13) per SD change), mostly confined to men and younger subjects but with greater sex similarity trends for CHF. Slightly increased risks were seen for the lowest Hb levels in the elderly and in females. IS risk was positively and more linearly associated to Hb. Interpretation. In AMORIS the highest AMI and CHF risks were found in the upper region of the distribution, but different shapes of relationships according to age and gender were found. IS associated positively with Hb. Key words: [ABSTRACT FROM AUTHOR]

Abstract: LDL (Low Density Lipoprotein) is considered the major atherogenic lipoprotein whereas HDL (High Density Lipoprotein) is anti-atherogenic. In recent years also non-HDL cholesterol as well as TG (triglycerides) are included in guidelines defining cardiovascular (CV) risk and target values during lipid lowering treatment. In recent years apolipoproteins (apo) B, reflecting atherogenic, and apoA-I reflecting anti-atherogenic lipoproteins, have been shown to be superior to conventional lipids in predicting risk and reduction of events in lipid lowering trials using statins. These new data are reviewed. The apoB/apoA-I ratio, which reflects the cholesterol balance of the “bad” and “good” lipids, is a simple and accurate summary index of CV risk and it is better than the conventional LDL and other lipids as a risk marker and taget for therapy. [Copyright &y& Elsevier]

Hypercholesterolemia and hypertriglyceridemia are risk factors for cardiovascular disease. The potentially atherogenic very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), large buoyant, and small dense low-density lipoprotein (LDL) particles are all transported by apolipoprotein (apo) B, one protein per particle. The anti-atherogenic HDL contains apoA-I. In the apolipoprotein-related mortality risk (AMORIS) study, 98,722 males and 76,831 females aged 20–80 years were investigated at health check-ups. They were followed for 98 months, and 1267 males and 586 females died from myocardial infarction. The aim of the study is to investigate if apoB and apoA-I are more closely related to cardiac risk than lipids. The most common lipid phenotype in those who died was combined hypercholesterol- and hypertriglyceridemia (type IIB, 48%), followed by isolated hypercholesterolemia (type IIA, 40%). However, irrespective of lipid phenotype, and also in subjects with normal lipids, the highest CV risk was seen in those with a high apoB/apoA-I (>0.9 in males, >0.8 in females) compared with those with values below these cut-points. It is concluded that the balance of apoB/apoA-I is a simple and precise indicator strongly reflecting CV risk irrespective of lipid levels or combinations of lipids. [Copyright &y& Elsevier]

Background and aims Previous epidemiological studies have shown positive associations between serum calcium concentration and risk of cardiovascular disease (CVD), but results differ by definition of CVD. We examined the association of circulating calcium with incident and fatal CVD, myocardial infarction (MI), and stroke in the Swedish AMORIS cohort. Methods We included 441,738 participants of the AMORIS database linked for follow-up information on morbidity and mortality. Concentrations of total calcium were fully automated measured using a colorimetric method; concentrations of albumin were measured with a bromocresol green method between 1985 and 1995. The association of albumin-corrected calcium concentration and risk of incident and fatal CVD, MI, and stroke, respectively, was assessed with multivariable adjusted Cox proportional hazards models. Results Until December 31, 2011, during a median follow-up time of 21 years, 90,866 incident cases of CVD, 21,271 of MI, and 25,810 of stroke were identified. High serum calcium concentrations were associated with increased risk of non-fatal CVD (Hazard ratio [HR] = 1.12, 95% CI 1.10–1.14, top [≥2.40 nmol/L] vs. bottom [≤2–25 nmol/L] quintile), MI (1.19, 1.14–1.25), and stroke (1.11, 1.06–1.15) and fatal disease (CVD: 1.41, 1.35–1.47; MI: 1.41, 1.31–1.51; stroke: 1.30, 1.20–1.41). Effect modification by sex was observed for incident disease such that associations were stronger among women than men. Serum calcium was positively associated with both incident and fatal ischemic stroke and with fatal hemorrhagic stroke, but not with incident hemorrhagic stroke. In a sub-groups analysis, the results remained significant after adjustment for smoking. Conclusions The results support a modest positive association between serum calcium and risk of CVD, but the underlying mineral metabolism and the exact mechanisms are currently unclear. [ABSTRACT FROM AUTHOR]