The Relationship Between HHcy and Contrast-induced Nephropathy in Hypertensive Patients After Coronary Artery Diagnosis and Treatment
Condition: Homocysteine; Coronary Disease; Angioplasty,Balloon,Coronary; Contrast Media; Nephropathy; Hypertension
MeSH terms: Kidney Diseases; Hypertension; Coronary Disease
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Contrast-induced nephropathy has become the third-largest cause of hospital acquired acute
      renal injury, and which morbidity is only less than that of renal hypoperfusion and renal
      toxicity of drugs, about 11%of all cases. Pathophysiologic mechanisms of contrast-induced
      nephropathy(CIN) is not entirely clear yet. May be associated with renal hemodynamic changes,
      medullary ischemia because of renal blood flow reduction, oxidative stress, endothelial
      dysfunction ,contrast agents damage the epithelium of renal tubular directly and so on.
      Currently the studies have proved that inflammation(CRP, TNF-α and NF-қB) played a role in
      CIN.It is well-know that the hyperhomocysteinemia(HHCY) is a independent risk factor for
      cardiovascular diseases, which has pro-inflammatory effects. Researches showed that Hcy
      stimulated CRP generation by the NMDAr-ROS-ERK1 / 2 / p38-NF-қB signaling pathway and
      triggered inflammatory response. We will compare the CIN incidence of different plasma Hcy
      levels in adults hypertensive patients undergoing coronary artery diagnosis and treatment(CAG
      and PCI). CIN was defined as an absolute ≥0.5mg/dl or a relative ≥25% increase in the serum
      creatinine level at 48 hours after the procedure. The relationship between decreased plasma
      Hcy levels and blood pressure values by using Enalapril Maleate and Folic Acid Tablets(as the
      program-based antihypertension) and recovery of CIN has been observed. Using univariate and
      multivariate Logistic regression to analyse the relationship between HHcy and CIN, and taking
      receiver operating characteristic (ROC) curve to select the best Hcy plasma levels that which
      can predict the CIN and the probability. This study will help us to understand the
      relationship between HHcy and CIN that course of the procedure in adults hypertensive
      patients, preoperative plasma Hcy levels can predict the incidence of CIN and whether
      Enalapril Maleate Folic Acid tablets can reduce the CIN of hypertensive patients with HHcy.
      Which has important clinical significance. This study also offer feasibility for further
      research that HHcy plays a role in pathogenesis and specific signaling pathways of CIN.
    

Detailed description: 
      The first stage: the establishment of hypothesis of the relationship between HHcy and CIN The
      demographic and laboratory data were retrieved from the His system. Hypertensive patients who
      underwent coronary artery diagnosis and treatment(CAG or PCI) at Fuling Central Hospital of
      Chongqing City from June 2013 to August 2015 were initially included in the present study.
      The baseline characteristics of the hypertensive patients according to the tertile of plasma
      homocysteine level will be analysed, and investigating the incidence of CIN and relevant
      factors.

      The second stage: To verify the hypothesis of relationship between HHcy and CIN in patients
      with hypertension CER research method

        1. patients who accepted the coronary artery diagnosis and treatment(CAG and PCI ) in
           departments of Geriatrics and Cardiovascular within one year were initially participate
           in. According to the statistics that we finished, the proportion of hypertension in the
           total patients who underwent procedure has reached about 80%, so there has more than
           4000 patients with hypertension within 1 year will be involved. The levels of plasma Hcy
           in the total patients will be detected. The patients will divided into 2 groups
           according to the plasma Hcy levels,The hypertensive patients(adults) with their plasma
           Hcy levels ≥10 umol/L will take Enalapril Maleate and Folic Acid Tablets(as the
           program-based antihypertension), The hypertensive patients(adults) with their plasma Hcy
           levels <10 umol/L will take Enalapril Maleate Tablets(as the program-based
           antihypertension).The procedure will be carried out after blood pressure valves within
           normal range.

        2. All patients will be followed up for 3 months, they will return to hospital 3 times(once
           a month) after discharged. Urine routine and renal function will be tested, to register
           blood pressure,any change of body condition and other related factors per months, and
           plasma Hcy levels will be detected in the hypertensive patients with
           higher-homocysteinemia at second and third months after discharged.

        3. Data collection and data statistics will be carried out per 2 months. All patients who
           undergoing coronary artery diagnosis and treatment(CAG and PCI)will be divided into
           group A without hypertension, group B that the hypertensive patients with their plasma
           Hcy levels <10 umol/L and group C that the hypertensive patients with plasma Hcy levels
           ≥10 umol/L. To compare CIN incidence of the 3 groups at each time point, the CIN
           incidence of group B and group C will be compared, and association between CIN and the
           levels of blood pressure and plasma Hcy will be analyzed by multivariate logistic
           regression analysis according to the ROC curve.
    

Intervention name(s): Enalapril Maleate Tablets(as the program-based antihypertension); Enalapril Maleate and Folic Acid tablets(as the program-based antihypertension); Placebo
Intervention type(s): Drug; Drug; Drug
Intervention MeSH terms: Folic Acid; Enalapril; Enalaprilat; Maleic acid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Hyperhomocysteinemia; Coronary angiography; Percutaneous coronary intervention; Hypertension; Contrast-induced nephropathy