Serum inflammatory markers in relation to prostate cancer severity and death in the Swedish AMORIS study.

Inflammation is a well-documented driver of cancer development and progression. However, little is known about its role in prostate carcinogenesis. Thus, we examined the association of C-reactive protein (CRP), haptoglobin, albumin and white blood cells (WBC) with prostate cancer (PCa) severity (defined by PCa risk category and clinicopathological characteristics) and progression (defined by PCa death). We selected 8,471 Swedish men with newly diagnosed PCa who had exposure measurements taken approximately 14 years prior to diagnosis. We calculated odds ratio (OR) and 95% confidence interval (CI) for the associations between the inflammatory markers and PCa severity using logistic regression, while Cox proportional hazard regression was used for the associations with overall and PCa death. Serum CRP levels were associated with increased odds of high risk and metastatic PCa, and high PSA levels (≥20 µg/L) (OR: 1.29; 95% CI: 1.06-1.56, 1.32; 1.05-1.65 and 1.51; 1.26-1.81, respectively). Similarly, higher haptoglobin levels were associated with increased odds of metastatic PCa, high PSA level and possibly high grade PCa (1.38; 1.10-1.74, 1.50; 1.17-1.93 and 1.25; 1.00-1.56, respectively). Albumin was positively associated with Gleason 4 + 3 tumour (1.38; 1.02-1.86) and overall death (HRunit increase in log : 1.60; 95% CI: 1.11-2.30), but inversely associated with high risk PCa and high PSA levels (≥20 µg/L) (0.71; 0.56-0.89 and 0.72; 0.5 9-0.90). WBC was associated with increased odds of T3-T4 PCa. Except for albumin, none of these markers were associated with PCa death or overall death. Systemic inflammation as early as 14 years prior to diagnosis may influence prostate cancer severity.

Low fructosamine and mortality - A long term follow-up of 215,011 non-diabetic subjects in the Swedish AMORIS study.

BACKGROUND AND AIMS: Both high and low fasting glucose has been associated with an increased mortality among individuals without diabetes. This J-shaped association has also been shown for HbA1c in relation to all-cause mortality. High fructosamine is associated with increased mortality. In this study we aim to evaluate if low fructosamine is also associated with increased mortality in non-diabetic subjects. METHODS AND RESULTS: We included 215,011 subjects from the AMORIS cohort undergoing occupational health screening or primary care in Stockholm, Sweden. Cause specific mortality was obtained from the Swedish Cause-of-Death Register by record linkage. Hazard ratios for the lowest decile of fructosamine were estimated by Cox regression for all-cause (n = 41,388 deaths) and cause-specific mortality during 25 years of follow-up. We observed gradually increased mortality with lower fructosamine in a large segment of the population. In the lowest decile of fructosamine the sex, age, social class and calendar adjusted hazard ratio was 1.20 (95% CI; 1.18-1.27) compared to deciles 2-9. This increased mortality was attenuated after adjustment for six other biomarkers (HR = 1.11 (95% CI; 1.07-1.15)). Haptoglobin, an indicator of chronic inflammation, made the greatest difference in the point estimate. In sensitivity analyses we found an association between low fructosamine and smoking and adjustment for smoking further attenuated the association between low fructosamine and mortality. CONCLUSION: Low levels of fructosamine in individuals without diabetes were found to be associated with increased mortality. Smoking and chronic inflammation seem to at least partially explain this association but an independent contribution by low fructosamine cannot be excluded.

Fructosamine is a risk factor for myocardial infarction and all-cause mortality - Longitudinal experience from the AMORIS cohort.

BACKGROUND AND AIMS: Glycation is linked to microvascular complications of diabetes and also to macrovascular events. Fructosamine is a biomarker of glycation but its associations to macrovascular complications are not well documented. The aim of this study was to evaluate fructosamine as a predictor of myocardial infarction and all-cause mortality in a large population based cohort. METHODS AND RESULTS: Information on glucose and fructosamine was obtained from subjects of the AMORIS cohort (n = 338,443) followed for 19 years on average. Incident cases of myocardial infarction and death from any cause were identified from national patient and cause of death register respectively. The incidence of myocardial infarction (n = 21,526 cases) and all-cause mortality (n = 73,458 deaths) increased at a fructosamine of 2.30 mmol/L or above. For myocardial infarction, the sex-age- fasting- and entry period adjusted hazard ratio in subjects above 2.70 mmol/L vs. reference range subjects was 2.88 (95% CI: 2.70-3.07). The corresponding hazard ratio for all-cause mortality was 2.31 (95% CI: 2.21-2.41). These associations remained basically unchanged after adjustment for total cholesterol, triglycerides, albumin, social class, smoking and hypertension. When additional adjustment for glucose was performed the associations were attenuated but remained. In a sub cohort with simultaneous measurements of fructosamine, HbA1c and fasting glucose respectively similar associations were observed (n = 9746). CONCLUSION: There is a strong association between fructosamine and myocardial infarction and death from any cause when major cardiovascular risk factors are accounted for. In addition, this association could only partly be explained by glucose levels.

Renal function assessed by two different formulas and incidence of myocardial infarction and death in middle-aged men and women.

BACKGROUND: Chronic kidney disease predicts mortality in the general population, but less is known about the association with incidence of first myocardial infarction. We evaluated glomerular filtration rates (GFR) estimated by the Modification of Diet in Renal Disease study (GFR-MDRD) equation and the Mayo formula (GFR-Mayo) as predictors of myocardial infarction and death. METHODS: In 571 353 Swedish men and women, undergoing health controls, with mean age 45 years, and no previous myocardial infarction, hazard ratios were calculated to assess the association between renal function and incidence of myocardial infarction and all-cause mortality, respectively. Glomerular filtration rate 60-90, 30-60 and <30 mL per minute per 1.73 m(2), was defined as mildly, moderately and severely decreased GFR, respectively. RESULTS: There were 19 510 myocardial infarctions and 56 367 deaths during 11.6 years of follow-up. Hazard ratios (and 95% confidence intervals) for myocardial infarction, using GFR-Mayo were 1.11 (1.06-1.16) for mildly, 1.32 (1.18-1.48) for moderately and 2.54 (1.90-3.40) for severely decreased GFR. The corresponding figures for GFR-MDRD were 1.01 (0.96-1.05), 1.23 (1.14-1.32) and 2.49 (1.85-3.35). Mortality was increased at all levels of reduced GFR-Mayo and at moderately or severely decreased GFR-MDRD. CONCLUSIONS: Already mildly decreased GFR increase the risk of myocardial infarction and death in the general population. The association with adverse outcomes is stronger when GFR-Mayo rather than GFR-MDRD is used to assess renal function.

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.

Relationships between lipoprotein components and risk of ischaemic and haemorrhagic stroke in the Apolipoprotein MOrtality RISk study (AMORIS).

OBJECTIVES: To compare lipoprotein components associated with ischaemic and haemorrhagic stroke by age and gender in the Apolipoprotein MOrtality RISk (AMORIS) Study (n=148 600). DESIGN: Prospective follow-up study (11.8, range 7-17 years) of fatal and nonfatal ischaemic and haemorrhagic stroke through linkage with Swedish hospital discharge and mortality registers. SETTING: Measurements of lipoprotein components from health check-ups in the larger Stockholm area. RESULTS: Ischaemic stroke was more common than haemorrhagic stroke (5 :1), but case fatality was higher in haemorrhagic stroke. An elevated apoB/apoA-1 ratio and triglycerides, non-HDL cholesterol, low HDL cholesterol, and the total cholesterol to high-density cholesterol (TC/HDL-C) ratio were associated with increased incidence of nonfatal and fatal ischaemic stroke as well as all cerebrovascular events (n=7480) in both genders. The associations were somewhat stronger for nonfatal than fatal events. In ischaemic stroke the apoB/apoA-1 ratio was a stronger predictor than the TC/HDL-C ratio in all subjects, in those below 65 years of age and in those with LDL-C below 3 mmol L(-1). Haemorrhagic stroke was not associated with elevated atherogenic lipoproteins except for increased risk of fatal haemorrhagic stroke in women with a high apoB/apoA-I ratio. CONCLUSIONS: Dyslipidaemia is associated with an increased risk of ischaemic stroke but few relations were seen in haemorrhagic stroke. Use of the apoB/apoA-I ratio as a marker of dyslipidaemia is at least as efficient as conventional lipids, for the identification of subjects at increased risk of stroke, especially ischaemic stroke. Practical advantages, fasting is not needed, speak in favour of using apoB and apoA-1 in stroke risk prediction.

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. DESIGN: Prospective study (11.8 years, range 7-17) of fatal and nonfatal acute myocardial infarction, stroke and CHF through linkage with Swedish hospital discharge and mortality registers. SETTINGS: Measurements of uric acid in 417,734 men and women from health check-ups in Stockholm area. RESULTS: There was a gradual increase in risk of AMI, stroke and CHF by increasing UA levels. Women had a stronger relationship between UA and both AMI and IS than men. Predictions of AMI were at least as powerful in the elderly as in the young, but not so for IS. Associations were markedly attenuated when adjusted for total cholesterol, triglycerides, hospital hypertension and diabetes status. The association between UA and HS was U-shaped in both genders. CHF was more strongly related to UA than AMI and stroke and less affected by the adjustment factors. CONCLUSIONS: Already moderate levels of UA appear to be associated with an increased incidence of AMI, stroke and CHF in middle-aged subjects without prior cardiovascular disease. These associations seem to increase gradually from lower to higher levels of UA. UA may be an important complementary indicator of cardiovascular risk in the general population.

Relationships between lipoprotein components and risk of myocardial infarction: age, gender and short versus longer follow-up periods in the Apolipoprotein MOrtality RISk study (AMORIS).

OBJECTIVES: Examine and compare lipoprotein components associated with fatal and nonfatal acute myocardial infarction (AMI) by time period in the Apolipoprotein MOrtality RISk (AMORIS) Study. DESIGN: Prospective follow-up study of nonfatal and fatal myocardial infarction through linkage with Swedish hospital discharge and Swedish mortality registers. SETTING: Measurements of lipoprotein components from health check-ups in the larger Stockholm area. SUBJECTS: The AMORIS subjects (n = 149 121) free of AMI at blood sampling were followed from 1985 to 2002 with respect to n = 6794 first cases of AMI. RESULTS: Hazard ratios of nonfatal and fatal AMI by lipoprotein parameters were highly significant and about equally strong in both genders. Apolipoprotein B (apoB), nonhigh density cholesterol and low density cholesterol predicted nonfatal AMI (NFAMI) better than fatal AMI, but high density cholesterol or apolipoprotein A-1 did not. Atherogenic components were weaker predictors after 1997 than before. In multivariate analyses apoB/apoA-1 was a better predictor than TC/HDL-C. ApoB/apoA-1 added clinically significant information to TC/HDL-C in men as reflected by a net reclassification improvement (NRI) of 9.4% (P < 0.0001). CONCLUSION: ApoB, apoB/apoA-1 and non-HDL-C were found about equally predictive with LDL-C being slightly less, but multivariate analyses showed apoB/apoA-1 to be the strongest predictor. Attenuation of prediction ability between nonfatal and fatal AMI may be due to modern treatment of CHD after a NFAMI and attenuation of hazard ratios after 1997 may be due to selection of lower risk subjects surviving to 1997.

Lipoprotein(a): levels in a Swedish population in relation to other lipid parameters and in comparison with a male Sri Lankan population.

OBJECTIVE: To evaluate differences in Lipoprotein (a) [Lp(a)] concentrations between a Swedish and Sri Lankan population. METHODS: The distribution of Lp(a) and its relation to other lipid parameters, measured with an automated turbidimetric method, in 4646 Swedes (1944 females and 2702 males) undergoing health screening and 757 randomly selected Sri Lankan males (667 non-CHD and 80 CHD subjects) was evaluated. RESULTS: The distribution was highly skewed towards low values in both the Swedish population and the Sri Lankan male population. The Swedish population had a median of 0.16 g/L (reported as total mass) whereas the Sri Lankan population median of 0.06 g/L was much lower. For the Swedes, there was a small significant difference of 0.03 g/L between the sexes (F < M; p < 0.001) and Lp(a) was significantly higher in subjects > 50 years of age in both sexes (p < 0.002(F); p < 0.02(M)). 29% had Lp(a) values > 0.30 g/L. In the Sri Lankan males population Lp(a) was also significantly higher in subjects > 50 years of age (p < 0.009) but only 7% had an Lp(a) concentration of > 0.30 g/L. In the CHD subgroup, though not significant, subjects > 50 years of age had a lower Lp(a) concentration, indicating that Lp(a) may be a more significant risk factor in younger subjects. Both the Swedish female and male hypercholesterolemic subgroups had significantly higher Lp(a) concentrations than normolipemic subgroups and the male hypertriglyceridemic subgroups significantly lower Lp(a) concentrations than normolipemic. Great differences in Lp(a) levels are thus found between the two populations. The differences are similar in normolipemic subjects and probably they reflect mainly genetic differences. Lipid/lipoprotein concentrations were also found to differ. It is being investigated if this reflects differences in CHD prevalence. CONCLUSION: Our data support the importance of including Lp(a) measurements when assessing the risk profile for premature development of CHD in the individual patient.

Serum urate, serum glucose and diabetes.

We have studied the relationship between serum glucose and urate in 260,699 men and 214,118 women from Sweden, and 140,084 men and 30,653 women from the UK. We found an increase in mean serum urate with increasing glucose concentrations up to 7.0 mmol/L in men and 9.0 mmol/L in women. Thereafter increasing glucose values were accompanied by a statistically significant decrease in urate concentrations. This fall was particularly marked in younger subjects. We believe this may have important implications for the free radical status of diabetics.

The History of the AutoChemist®: From Vision to Reality.

OBJECTIVES: This paper discusses the early history and development of a clinical analyser system in Sweden (AutoChemist, 1965). It highlights the importance of such high capacity system both for clinical use and health care screening. The device was developed to assure the quality of results and to automatically handle the orders, store the results in digital form for later statistical analyses and distribute the results to the patients' physicians by using the computer used for the analyser. RESULTS: The most important result of the construction of an analyser able to produce analytical results on a mass scale was the development of a mechanical multi-channel analyser for clinical laboratories that handled discrete sample technology and could prevent carry-over to the next test samples while incorporating computer technology to improve the quality of test results. The AutoChemist could handle 135 samples per hour in an 8-hour shift and up to 24 possible analyses channels resulting in 3,200 results per hour. Later versions would double this capacity. Some customers used the equipment 24 hours per day. CONCLUSIONS: With a capacity of 3,000 to 6,000 analyses per hour, pneumatic driven pipettes, special units for corrosive liquids or special activities, and an integrated computer, the AutoChemist system was unique and the largest of its kind for many years. Its follower - The AutoChemist PRISMA (PRogrammable Individually Selective Modular Analyzer) - was smaller in size but had a higher capacity. Both analysers established new standards of operation for clinical laboratories and encouraged others to use new technologies for building new analysers.

The History of the Data Systems AutoChemist® (ACH) and AutoChemist- PRISMA (PRISMA®): from 1964 to 1986.

OBJECTIVES: This paper presents the history of data system development steps (1964 - 1986) for the clinical analyzers AutoChemist®, and its successor AutoChemist PRISMA® (PRogrammable Individually Selective Modular Analyzer). The paper also partly recounts the history of development steps of the minicomputer PDP 8 from Digital Equipment. The first PDP 8 had 4 core memory boards of 1 K each and was large as a typical oven baking sheet and about 10 years later, PDP 8 was a "one chip microcomputer" with a 32 K memory chip. The fast developments of PDP 8 come to have a strong influence on the development of the data system for AutoChemist. Five major releases of the software were made during this period (1-5 MIACH). RESULTS: The most important aims were not only to calculate the results, but also be able to monitor their quality and automatically manage the orders, store the results in digital form for later statistical analysis and distribute the results to the physician in charge of the patient using thesame computer as the analyzer. Another result of the data system was the ability to customize AutoChemist to handle sample identification by using bar codes and the presentation of results to different types of laboratories. CONCLUSIONS: Digital Equipment launched the PDP 8 just as a new minicomputer was desperately needed. No other known alternatives were available at the time. This was to become a key success factor for AutoChemist. That the AutoChemist with such a high capacity required a computer for data collection was obvious already in the early 1960s. That computer development would be so rapid and that one would be able to accomplish so much with a data system was even suspicious at the time. In total, 75; AutoChemist (31) and PRISMA (44) were delivered Worldwide. The last PRISMA was delivered in 1987 to the Veteran Hospital Houston, TX USA.

The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases.

Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.

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.

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. SUBJECTS AND DESIGN: A total of 98 722 men and 76 831 women were recruited from screening programmes. The prospective risk and the relationships between five different types of fatal strokes and the lipid fractions, apoB, apoA-I and the apoB/apoA-I ratio (automated immunoturbidimetry) were examined. The results were compared with the risks of other ischaemic and non-ischaemic fatalities. RESULTS: Mean follow-up was 10.3 years. High apoB and low apoA-I values were significantly related to risk of stroke. The odds ratio comparing the upper 10th versus the 1st decile of the apoB/apoA-I ratio for all strokes adjusted for age, gender, total cholesterol (TC) and triglycerides (TG) was 2.07 (95% CI: 1.49-2.88), P < 0.0001. The strongest association was for ischaemic stroke. Low apoA-I was a common abnormality in all stroke subtypes including subarachnoidal and haemorrhagic strokes. In multivariate analyses the apoB/apoA-I ratio was a stronger risk predictor than total/HDL and LDL/HDL cholesterol ratios. The apoB/apoA-I ratio was linearly related to the risk of stroke although the slope was less than observed for the risk of fatal myocardial infarction. For all ischaemic events pooled together the age-, gender-, TC- and TG-adjusted odds ratio, 10th vs. 1st decile, was 3.13 (95% CI: 2.66-3.69), P < 0.0001. By contrast, there was no relationship between the apoB/apoA-I ratio and risk of cancer or any other non-ischaemic causes of death. CONCLUSIONS: These observations link the apoB/apoA-I ratio to the risk of fatal stroke in a similar fashion as for myocardial infarction and other ischaemic events. Our findings indicate that the apoB/apoA-I ratio, which indicates the 'cholesterol balance', is a robust and specific maker of virtually all ischaemic events.

Errors that result from using the TC/HDL C ratio rather than the apoB/apoA-I ratio to identify the lipoprotein-related risk of vascular disease.

The objective of this analysis was to demonstrate the frequency and extent of error that results from using the TC/HDL C ratio rather than the apoB/apoA-I ratio to estimate the lipoprotein-related risk of vascular disease within 94,667 men and 75,675 women in the Apoprotein-related Mortality Risk (AMORIS) cohort. The odds ratio (OR) for the risk of fatal myocardial infarction was determined for 1 SD change in the apoB/apoA-I ratio and all the conventional cholesterol ratios--TC/HDL C ratio, LDL C/HDL C ratio, non-HDL C/HDL C ratio. In both men and women, the apoB/apoA-I ratio was significantly greater than any of the cholesterol ratios, which, in fact, differed little. Therefore, the apoB/apoA-I ratio was taken as the most accurate index of the lipoprotein-related risk of vascular disease. Using Receiver Operating Characteristic analysis, it was demonstrated that the diagnostic accuracy of the apoB/apoA-I ratio was significantly greater than any cholesterol ratio in those with an LDL cholesterol <3.6 mmol L(-1) compared to those with an LDL cholesterol >3.6 mmol L(-1). Indeed, the difference between the apoB/apoA-I OR compared with the TC/HDL C OR progressively widened as risk increased. This suggests that the advantage of the apoB/apoA-I ratio is greatest in the population at highest risk. The distribution of subjects by quintiles showed in both genders that whilst agreement was greatest at the extremes, even at these points there was substantial discordance between the TC/HDL C and the apoB/apoA-I ratios. Within the middle of the distribution, less than 50% of the values were concordant. Finally, when comparing the ORs, the TC/HDL C ratio underestimated risk in 69.4% of male subjects and overestimated risk in 26.1% of male subjects, whereas in the female subjects, the TC/HDL C ratio underestimated risk in 84.9% of the subjects and overestimated risk in 12.0%. Thus, using the conventional cholesterol ratios rather than the apoB/apoA-I ratio results in frequent and substantial error in the estimation of the lipoprotein-related risk of vascular disease.

Apo B versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirty-person/ten-country panel.

There is abundant evidence that the risk of atherosclerotic vascular disease is directly related to plasma cholesterol levels. Accordingly, all of the national and transnational screening and therapeutic guidelines are based on total or LDL cholesterol. This presumes that cholesterol is the most important lipoprotein-related proatherogenic risk variable. On the contrary, risk appears to be more directly related to the number of circulating atherogenic particles that contact and enter the arterial wall than to the measured concentration of cholesterol in these lipoprotein fractions. Each of the atherogenic lipoprotein particles contains a single molecule of apolipoprotein (apo) B and therefore the concentration of apo B provides a direct measure of the number of circulating atherogenic lipoproteins. Evidence from fundamental, epidemiological and clinical trial studies indicates that apo B is superior to any of the cholesterol indices to recognize those at increased risk of vascular disease and to judge the adequacy of lipid-lowering therapy. On the basis of this evidence, we believe that apo B should be included in all guidelines as an indicator of cardiovascular risk. In addition, the present target adopted by the Canadian guideline groups of an apo B <90 mg dL(-1) in high-risk patients should be reassessed in the light of the new clinical trial results and a new ultra-low target of <80 mg dL(-1) be considered. The evidence also indicates that the apo B/apo A-I ratio is superior to any of the conventional cholesterol ratios in patients without symptomatic vascular disease or diabetes to evaluate the lipoprotein-related risk of vascular disease.

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.