**7.3. The apo-ratio in relation to chronic kidney disease and MI risk in the AMORIS study**

Some previous studies have shown apoB to be increased and apoA-I to be decreased in patients with renal insufficiency. In the much larger AMORIS study Holzmann et al. (93) performed in 142,394 middle-aged mainly healthy men and women it was shown that the apo-ratio, the TC/HDL-C ratio, and non-HDL-C all are strong predictors of first MI, among both men and women, with or without chronic kidney disease (CKD). Those with the lowest glomerular filtration rate (estimated GFR mL/min/1.73 m2, n = 5,838) had the highest aporatio. In Receiver Operator Characteristics (ROC) analysis the area under the curve (AUC) for the apo-ratio was 0.77 for men and 0.83 for women without CKD, and 0.65 and 0.74 among men and women with CKD, respectively analyses. These and other data reflect a certain advantage in the prediction of MI for the apo-ratio as compared to conventional lipids. Furthermore, the findings also indicate the presence of severe atherosclerosis both in the kidney and in the coronary arteries.

#### **7.4. The apo-ratio and risk of stroke in the AMORIS study**

High LDL-C is a major risk factor for MI. However, LDL-C is rarely increased in those who suffer any type of stroke. A low HDL-C and some abnormalities in either apoB and/or apoA-I have previously been found in patients with ischaemic stroke (94-99). In 2006 Walldius et al. published the first report on risk of stroke based on the AMORIS-population (100). The relationships between different types of fatal stroke and the lipid fractions, apoB, apoA-I and the apo-ratio were examined in 98,722 men and 76,831 women followed for a mean of 10.3 years. High apoB and low apoA-I values were significantly related to risk of stroke. The odds ratio comparing the upper 10th vs. the 1st decile of the apo-ratio for all strokes adjusted for age, gender, TC and TG was 2.07 (95% CI: 1.49–2.88, p < 0.0001). The apo-ratio was linearly related to the risk of stroke although the slope was less than observed for the risk of fatal MI (**Figure 6, left)**. Low apoA-I was a common abnormality in all stroke subtypes including subarachnoidal and haemorrhagic strokes. In multivariate analyses the apo-ratio was a significantly stronger risk predictor than TC/HDL-C and LDL-C/HDL-C ratios.

**Figure 6.** Risk of total stroke (left) (reference 3 and 100) and ischemic stroke (right) (reference 101). Both figures from the AMORIS study.

In a prospective follow-up study (mean observation age 11.8, range 7–17 years) based on the AMORIS population (n = 148,600). Holme et al. focused on risk of fatal and non-fatal ischaemic and haemorrhagic stroke in relation to all lipids and apos (101). Hazard ratio of non-fatal and fatal ischaemic and haemorrhagic stroke for 1 SD difference in lipoprotein components was calculated by gender, adjusted for age, MI, diabetes and hypertension. Ischaemic stroke was more common than haemorrhagic stroke (5:1), but case fatality was higher in haemorrhagic stroke. The apo-ratio, non-HDL-C and TG as well as low HDL-C and a high TC/HDL-C ratio were all predictors of ischemic stroke **(Figure 6, right)** and all cerebrovascular events (n=7,480) with somewhat stronger relations for non-fatal than fatal events. The apo-ratio was significantly stronger than the TC/HDL-C ratio in the patients with ischaemic stroke as reflected by chi-squared information value, adjusted for hypertension, diabetes, AMI, age and gender. The strongest association was for ischaemic stroke in those < 65 years of age and also for those with LDL-C < 3.0 mmol/L. There were no lipid relations to risk of haemorrhagic stroke other than a high apo-ratio related to risk in women.

#### **7.5. Other findings from AMORIS indicating that the apo-ratio predicts CV risk**

In addition, the risk of death from aortic aneurysms (n = 241) was significantly related to the apo-ratio (p< 0.0039) (3) adding to the importance of the apo-ratio as a predictor of severe ischaemic complications related to atherosclerosis. In that paper we also noted that, there was no relationship between the apo-ratio and risk of cancer (n = 4,423), motor vehicle accidents (n =100) or dementia (n = 255).
