TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: Although the C5 variant of cholinesterase is known to be a cause of hypercholinesterasemia, the pathophysiological significance of the C5 variant and the C5 variant-related hypercholinesterasemia in cardiovascular diseases remain unclear. The present study aimed to clarify the pathophysiological significance of the C5 variant as a risk or protective factor for coronary artery disease (CAD) in patients with severe hypercholinesterasemia.', 'Severe hypercholinesterasemia was defined as serum cholinesterase (ChE) activity >= 450 IU/L (>= 2.0 SD). We screened 11,648 consecutive outpatients between 2005 and 2011 at Toho University, Sakura Medical Center. In patients with severe hypercholinesterasemia, phenotyping of the C5 variant was conducted using polyacrylamide gel electrophoresis and alpha-naphthyl butyrate staining.', '157 subjects (1.4% of 11,648 outpatients screened) were diagnosed with severe hypercholinesterasemia (mean serum ChE activity 574 ± 109 IU/L), and the frequency of the C5 variant was 45.2%. Subjects with the C5 variant had higher age, lower body mass index, milder dyslipidemia and liver dysfunction, and lower rates of hypertension and CAD compared with subjects without the C5 variant. Multivariate logistic regression model demonstrated that the presence of C5 variant independently lowered the risk of CAD, with odds ratio 0.071 (95% confidence interval (CI) 0.007 - 0.763, p = 0.029).\Question: Is c5 variant associated with decreased risk of coronary artery disease in outpatients with severe hypercholinesterasemia?

SOLUTION: The prevalence of the C5 variant was relatively high, and the C5 variant is associated with decreased risk of CAD in outpatients with severe hypercholinesterasemia.

PROBLEM: Context: Inflammation has been implicated in the initiation, progression and manifestation of hypertensive heart disease. We sought to determine the role of monocytes/macrophages in hypertension and pressure overload induced left ventricular (LV) remodeling.', 'We used two models of LV hypertrophy (LVH). First, to induce hypertension and LVH, we fed Sabra salt-sensitive rats with a high-salt diet. The number of macrophages increased in the hypertensive hearts, peaking at 10 weeks after a high-salt diet. Surprisingly, macrophage depletion, by IV clodronate (CL) liposomes, inhibited the development of hypertension. Moreover, macrophage depletion reduced LVH by 17% (p<0.05), and reduced cardiac fibrosis by 75%, compared with controls (p=0.001). Second, to determine the role of macrophages in the development and progression of LVH, independent of high-salt diet, we depleted macrophages in mice subjected to transverse aortic constriction and pressure overload. Significantly, macrophage depletion, for 3 weeks, attenuated LVH: a 12% decrease in diastolic and 20% in systolic wall thickness (p<0.05), and a 13% in LV mass (p=0.04), compared with controls. Additionally, macrophage depletion reduced cardiac fibrosis by 80% (p=0.006). Finally, macrophage depletion down-regulated the expression of genes associated with cardiac remodeling and fibrosis: transforming growth factor beta-1 (by 80%) collagen type III alpha-1 (by 71%) and atrial natriuretic factor (by 86%).\Question: Do macrophages dictate the progression and manifestation of hypertensive heart disease?

SOLUTION: Macrophages mediate the development of hypertension, LVH, adverse cardiac remodeling, and fibrosis. Macrophages, therefore, should be considered as a therapeutic target to reduce the adverse consequences of hypertensive heart disease.

PROBLEM: Context: 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.', 'Plasma lipids, lipoproteins, apoB, and apoA-I were measured in 69,030 men and 57,168 women above 40 years of age. After a mean follow-up of 98 months, 1183 men and 560 women had died from a myocardial infarction in this prospective apolipoprotein-related mortality risk (AMORIS) study.', '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 <3.6 mmol/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.\Question: Is the apoB/apoA-I ratio better than the cholesterol ratios to estimate the balance between plasma proatherogenic and antiatherogenic lipoproteins and to predict coronary risk?

SOLUTION:
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.

