Plasma Mannose Associated Parameter Levels in Nondiabetic Coronary Artery Disease
Condition: Coronary Artery Disease; Hyperlipidemias
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Hyperlipidemias
Study type: Observational

Summary: 
      Aims: Nondiabetic patients have been studied to determine whether modest elevations in plasma
      mannose levels may be associated with a greater incidence of coronary artery disease (CAD).

      Methods: The plasma mannose, lipids (triglyceride, LDL, HDL, LDL, VLDL) and LDH levels were
      successfully will be evaluated with respect to subsequent coronary artery disease using
      records 120 nondiabetic patients and 120 healthy volunteers. CAD was identified from
      myocardial infarction and new diagnoses of angina.

      The associations between mannose levels and serum lipid parameters will be investigated.
    

Detailed description: 
      Coronary artery disease (CAD), also known as coronary heart disease (CHD) or ischemic heart
      disease (IHD), entails a decrease of blood flow to the heart muscle as a result of plaque
      build-up in the arteries of the heart. CAD are among the world's leading causes of mortality
      and morbidity, following rapid change and advancement of cardiovascular diagnosis and
      treatment methods.

      The broad range of lipid molecular species in human plasma and their possible role in human
      health and disease are topics of great interest. Plasma lipidome is now progressively
      recognized as a potentially important marker of chronic diseases, but the exact degree of its
      contribution to the interindividual phenotypic variation in family studies is uncertain .

      Associative evidence gathered from plasma lipidomic studies promises vital contributions to
      biomarker research-an important cornerstone of ongoing efforts to prevent chronic disease.
      The plasma lipidomic profile of humans is associated with various conditions including
      obesity and disorders of glucose metabolism, hypertension , cardiovascular diseases.

      Plasma lipids are solubilized and distributed by associating them with different protein
      groups. Most free fatty acids and associated structures with carboxyl functional groups
      interact with albumin, while more complex lipids are transported and distributed using plasma
      lipoproteins.

      Glycerolipids account for a high proportion of total lipids in plasma and include
      triacylglycerols (TAGs), diacylglycerols (DAGs), and ether-linked glycerolipids. The total
      plasma concentration of TAGs, allocated between chylomicrons and very-low-density lipoprotein
      (VLDL), depends on food intake. It is well known that various acquired or secondary risk
      factors (including genetic determinants, uncontrolled diabetes mellitus, obesity, and
      sedentary lifestyle) can cause hypertriglyceridemia, a prevalent type of dyslipidemia that is
      often associated with premature coronary artery disease.

      D-mannose, one of the stereoisomers forms, is a structural isomer of D-glucose and commonly
      found in biological systems, but L-mannose is generally not found in biological systems.
      Mannose is transported to mammalian cells by hexose transporters primarily by glucose
      transporters (GLUTs) present in the plasma membrane. Studies demonstrated that plasma mannose
      levels in human are associated with incident type 2 diabetes mellitus and cardiocascular
      diseases. On the other hand, molecular mechanism by which the pathway is induced is still
      unclear. A recent study showed that human plasma lipidome is pleiotropically associated with
      the cardiovascular risk factors and death.

      In mammalian cells, mannose is joined in glycolysis and gluconeogenesis pathways catalyzed by
      mannose phosphate isomerase. Mannose is a constituent of normal blood plasma and its
      concentration is generally elevated in diabetes mellitus and chronic glomerulonephritis .
      However, studies showed that fructose and mannose levels are significantly reduced in obese
      individuals . Currently, we have reported that elevated baseline mannose in plasma triggered
      to GLUT4 and Heksokinase-1 (HK1) associated with a progressive risk of CAD with time.

      A cytoplasmic enzyme of lactate dehydrogenase (LDH) found in all body cells which transfers a
      hydride from one molecule to another. LDH catalyzes the reversible conversion of pyruvate to
      lactate as a unit of Cori cycle. A cardiac marker of LDH is expressed extensively in body
      cells and a marker of heart failure .

      The aims of the study were to determine whether modest elevations in plasma mannose
      concentrations, and serum lipids [triglyceride, low density lipoprotein (LDL), high density
      lipoprotein (HDL) and very-low density lipoprotein (VLDL)] may be associated with a greater
      incidence of CAD among nondiabetic patients. Because hyperglycemia and/or hydrophilicity is
      associated with additional risk factors for CAD including hypertension, obesity, aging.
      Additionally, identifying the molecular and biochemical parameters in plasma associated with
      risk factors for CAD may have strategic importance in the treatment of these diseases.

      The patient and control groups will be initially informed about the study and obtained a
      written consent. Patients who underwent angiography at the Department of Cardiology and newly
      diagnosed as coronary artery disease and who weren't on statin treatment will be included in
      the patient group. The control group will be consisted of healthy people with normal coronary
      arteries angiographically. Patients with chronic renal failure, chronic liver disease,
      inflammatory disease, diabetes, insulin resistance, major metabolic or endocrine disease will
      be also excluded. For this purpose, age and sex matched 120 patients and 120 healthy
      volunteers will be admitted to study.

      Blood samples will be collected as described earlier into EDTA and citrate vacutainers.Total
      cholesterol, high-density lipoprotein and triglycerides will be measured by a commercially
      available enzymatic colorimetric assay (Roche, Basel,Switzerland). Glucose, creatinine and
      the other blood profiles will be determined by standard methods.The samples will be
      centrifuged at 400xg for 10 min to separate the serum.Biochemical parameters will be measured
      by using an Abbott ARCHITECH c800(Abbott Laboratories, USA) auto analyser and commercial
      kits. Serum mannose levels will be determined by enzymatic methods using in the ELISA.

      Kolmogrov-Smirnov test will be used to determine whether the group was parametrically
      distributed. Categorical variables were given as numbers and percentages. If the parameters
      are parametrically distributed, continuous variables will be expressed as mean ± standard
      deviation; if the parameters are non-parametrically distributed, continuous variables will be
      expressed as median (IQR). When parametric test assumptions will be provided, the
      significance test of difference between two means and one-way analysis of variance will be
      used to compare independent group differences. When parametric test assumptions were not
      provided, Mann-Whitney U test will be used to compare independent group differences. The
      relationships between continuous variables will be analyzed using Spearman correlation
      analysis, chi-square test will be used for analyzing categorical variables. Furthermore,
      Receiver Operating Characteristic (ROC) curve analysis was used for the discriminant
      performance serum mannose levels under investigation. In addition, the relationships between
      continuous variables will be examined by Spearman correlation analysis. P <0.05 will be
      considered statistically significant in all examinations.
    

Intervention name(s): Laboratory parameter levels in blood samples
Intervention type(s): Other
Intervention description(s): Mannose and lipid parameters (triglyceride, LDL, HDL, VLDL) will be analysed in blood samples by using ELISA method.
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        The patient and control groups will be initially informed about the study and obtained a
        written consent. Patients who underwent angiography at the Department of Cardiology and
        newly diagnosed as coronary artery disease and who weren't on statin treatment will be
        included in the patient group. The control group will be consisted of healthy people with
        normal coronary arteries angiographically. Patients with chronic renal failure, chronic
        liver disease, inflammatory disease, diabetes, insulin resistance, major metabolic or
        endocrine disease will also be excluded. For this purpose, age and sex matched 120 patients
        and 120 healthy volunteers will be admitted to study.
      
Biospecimen description: 
      Blood samples will be used.