Research On Association Of Coronary Heart Disease With Serum Cathepsin K And Osteoporosis In Elderly People

Background and purpose:Coronary heart disease(CHD)is the leading cause of death and disability in the elderly.Although its survival rate has improved in recent years,the number of death caused by CHD still ranks first.As the population of elderly grows more and more in the latest century,osteoporotic fracture largely results in inevitable death in people over 50 years old in China.The relationship between osteoporosis and CHD has attracted the attention of many researchers all over the world,and kept being a focus in the related field of research.Many clinical studies have shown that the incidence of CHD increases with the decrease of bone mineral density(BMD),but the mechanisms of this association involved are still not clearly elucidated.Cathepsin K(Cat K)is a member of the papain super family of lysosomal cysteine proteases,which is a cysteine protease with the highest expression and the strongest osteolytic activity in osteoclasts.Cat K also plays a critical role in bone resorption.Currently,the treatment of osteoporosis with Cat K inhibitors has been on the stage of clinical trials.It has been found that Cat K was closely related to intimal injury and atherosclerotic plaque formation,but no agreement has been made among researchers on how the Cat K level in serum correlates to CHD.The induction and expression of Cat K can be regulated by many cytokines.Tumor necrosis factor alpha(TNF-α)has been verified to regulate gene transcription through complex signaling pathways,thus maintaining the bone homeostasis.It is well known that heredity has influence on CHD,and TNF-α is one of the most promising candidate target genes to research on.The purpose of this study is to explore whether the serum level of Cat K is involved in the occurrence and development of atherosclerosisby measuring the serum level of Cat K in elderly people,and whether this process of atherosclerosis is related to inflammation,so as to provide some new ideas in the clinical treatment to prevent or slow down the progress of CHD.Methods:From June 2015 to June 2017,A total of 133 inpatients in geriatrics department of our hospital were enrolled,aged 60-93 years,with an average age of(74.8 ± 8.4)years.According to the diagnostic criteria of CHD established by the World Health Organization(WHO)in 1979,the CHD group(68 cases)was determined according to the results of coronary angiography,while the rest were nonCHD group(65 cases),excluding unstable angina pectoris,myocardial infarction,heart failure,secondary osteoporosis diseases,previous fractures andpatients who received anti-osteoporosis treatments or took drugs can lead to osteoporosis.All the enrolled patients were collected medical history,measured heightsand weights,anddetected theserum biochemistry,bone metabolism indexes,Cat K,matrix metalloproteinase(MMP)-9,osteoprotegerin(OPG),TNF-α.The BMD of lumbar spine 1-4(L1-4),femoral neck,intertrochanteric region,triangle area and trochanter of the enrolled patients were measured by dualenergy X-ray absorptiometry(DEXA).According to the diagnostic criteria of osteoporosis established by the WHO in 1998,the BMDmeasurements were divided into osteoporosis,osteopenia andnormal bone mass.The latter two were called non-osteoporosis in this study.Analyses were conducted on the correlations between Cat K and bone metabolism indexes and that between Cat K and CHD.SPSS 22.0 statistical software was applied for the data analysis.Results:1.The serum Cat K concentration and the prevalence of OP in CHD group were significantly higher than that in non-CHD group(P<0.05).2.Serum Cat K was positively associated with TNF-α 、 age 、 type 1 collagen cross-linked Ctelopeptide(CTX)、alkaline phosphatase(ALP)and high density lipoproteincholesterol(HDL-C)(P<0.01),contrary negatively associated with serum calcium(P<0.01),according to the linear regression analysis.3.Multiple logistic regression analysis showed that the serum Cat K(OR=1.022,95%CI 1.008~1.036,P<0.01)and BMD(OR=2.402,95%CI 1.294 ~ 4.462,P<0.01)were correlated with the morbidity of CHD in the elderly.Conclusion:The incidence of CHD in the elderly is closely related to the increase of serum Cat K level and the decrease of BMD.Serum Cat K may be expected to become a potential indicator for predicting the risk of CHD in the elderly with low bone mineral density.