1.Distribution and influencing factors of lipoprotein (a) levels in non-arteriosclerotic cardiovascular disease population in China
Yalei KE ; Lang PAN ; Jun LYU ; Dianjianyi SUN ; Pei PEI ; Yiping CHEN ; Ling YANG ; Huaidong DU ; Robert CLARKE ; Junshi CHEN ; Zhengming CHEN ; Xiao ZHANG ; Ting CHEN ; Runqin LI ; Litong QI ; Liming LI ; Canqing YU
Chinese Journal of Epidemiology 2024;45(6):779-786
Objective:To describe the distribution of lipoprotein (a) [Lp(a)] levels in non-arteriosclerotic cardiovascular disease (ASCVD) population in China and explore its influencing factors.Methods:This study was based on a nested case-control study in the CKB study measured plasma biomarkers. Lp(a) levels was measured using a polyclonal antibody-based turbidimetric assay certified by the reference laboratory and ≥75.0 nmol/L defined as high Lp(a). Multiple logistic regression model was used to examine the factors related to Lp(a) levels.Results:Among the 5 870 non-ASCVD population included in the analysis, Lp(a) levels showed a right-skewed distribution, with a M ( Q1, Q3) of 17.5 (8.8, 43.5) nmol/L. The multiple logistic regression analysis found that female was associated with high Lp(a) ( OR=1.23, 95% CI: 1.05-1.43). The risk of increased Lp(a) levels in subjects with abdominal obesity was significantly reduced ( OR=0.68, 95% CI: 0.52-0.89). As TC, LDL-C, apolipoprotein A1(Apo A1), and apolipoprotein B(Apo B) levels increased, the risk of high Lp(a) increased, with OR (95% CI) for each elevated group was 2.40 (1.76-3.24), 2.68 (1.36-4.93), 1.29 (1.03-1.61), and 1.65 (1.27-2.13), respectively. The risk of high Lp(a) was reduced in the HDL-C lowering group with an OR (95% CI) of 0.76 (0.61-0.94). In contrast, an increase in TG levels and the ratio of Apo A1/Apo B(Apo A1/B) was negatively correlated with the risk of high Lp(a), with OR (95% CI) of 0.73 (0.60-0.89) for elevated triglyceride group, and OR (95% CI) of 0.60 (0.50-0.72) for the Apo A1/B ratio increase group (linear trend test P≤0.001 except for Apo A1). However, no correlation was found between Lp(a) levels and lifestyle factors such as diet, smoking, and physical activity. Conclusions:Lp(a) levels were associated with sex and abdominal obesity, but less with lifestyle behaviors.
2.Protocol for the development and validation of a clinical measurement tool for fear of disease progression and recurrence in cardiac patients
Clarke Sarah T. ; Le Grande MICHAEL ; Murphy Barbara M. ; Robert HESTER ; Jackson Alun C.
Chronic Diseases and Translational Medicine 2024;10(3):195-204
Introduction::One in two cardiac patients fear having another heart event or their heart condition getting worse. Research in other chronic illnesses demonstrates that screening for fear of progression and recurrence is vital for adequately addressing such concerns in clinical care. The current project aims to develop and validate a measure for fear of progression and recurrence in cardiac patients.Methods::The Fear of Cardiac Recurrence and Progression Scale (FCRP) will be developed through a multistep process. An initial item pool will be generated through a review of the literature and existing measures and consultation with and feedback from key informants. The item pool will be tested in a sample of over 250 adults who have ever had an acute coronary event, undergone cardiac surgery, or a chronic cardiac condition. Exploratory factor analysis will be used to identify the underlying factors, and Rasch analysis will be used to reduce the number of items. A short form version of the FCRP will be developed for use as a brief screening tool, informed by clinical relevance and Rasch psychometric indices.Discussion::While many cardiac patients experience fears related to the progression or recurrence of their illness, there remains the need for a validated tool with which these concerns can be identified and measured. It is expected that the design and validation of the FCRP will aid identification of cardiac patients suffering from clinically significant levels of fear of progression and recurrence and facilitate the design of tailored psychological interventions to target these fears.
3.Protocol for the development and validation of a clinical measurement tool for fear of disease progression and recurrence in cardiac patients
Clarke Sarah T. ; Le Grande MICHAEL ; Murphy Barbara M. ; Robert HESTER ; Jackson Alun C.
Chronic Diseases and Translational Medicine 2024;10(3):195-204
Introduction::One in two cardiac patients fear having another heart event or their heart condition getting worse. Research in other chronic illnesses demonstrates that screening for fear of progression and recurrence is vital for adequately addressing such concerns in clinical care. The current project aims to develop and validate a measure for fear of progression and recurrence in cardiac patients.Methods::The Fear of Cardiac Recurrence and Progression Scale (FCRP) will be developed through a multistep process. An initial item pool will be generated through a review of the literature and existing measures and consultation with and feedback from key informants. The item pool will be tested in a sample of over 250 adults who have ever had an acute coronary event, undergone cardiac surgery, or a chronic cardiac condition. Exploratory factor analysis will be used to identify the underlying factors, and Rasch analysis will be used to reduce the number of items. A short form version of the FCRP will be developed for use as a brief screening tool, informed by clinical relevance and Rasch psychometric indices.Discussion::While many cardiac patients experience fears related to the progression or recurrence of their illness, there remains the need for a validated tool with which these concerns can be identified and measured. It is expected that the design and validation of the FCRP will aid identification of cardiac patients suffering from clinically significant levels of fear of progression and recurrence and facilitate the design of tailored psychological interventions to target these fears.
4.Minimal improvement in coronary artery disease risk prediction in Chinese population using polygenic risk scores: evidence from the China Kadoorie Biobank.
Songchun YANG ; Dong SUN ; Zhijia SUN ; Canqing YU ; Yu GUO ; Jiahui SI ; Dianjianyi SUN ; Yuanjie PANG ; Pei PEI ; Ling YANG ; Iona Y MILLWOOD ; Robin G WALTERS ; Yiping CHEN ; Huaidong DU ; Zengchang PANG ; Dan SCHMIDT ; Rebecca STEVENS ; Robert CLARKE ; Junshi CHEN ; Zhengming CHEN ; Jun LV ; Liming LI
Chinese Medical Journal 2023;136(20):2476-2483
BACKGROUND:
Several studies have reported that polygenic risk scores (PRSs) can enhance risk prediction of coronary artery disease (CAD) in European populations. However, research on this topic is far from sufficient in non-European countries, including China. We aimed to evaluate the potential of PRS for predicting CAD for primary prevention in the Chinese population.
METHODS:
Participants with genome-wide genotypic data from the China Kadoorie Biobank were divided into training ( n = 28,490) and testing sets ( n = 72,150). Ten previously developed PRSs were evaluated, and new ones were developed using clumping and thresholding or LDpred method. The PRS showing the strongest association with CAD in the training set was selected to further evaluate its effects on improving the traditional CAD risk-prediction model in the testing set. Genetic risk was computed by summing the product of the weights and allele dosages across genome-wide single-nucleotide polymorphisms. Prediction of the 10-year first CAD events was assessed using hazard ratios (HRs) and measures of model discrimination, calibration, and net reclassification improvement (NRI). Hard CAD (nonfatal I21-I23 and fatal I20-I25) and soft CAD (all fatal or nonfatal I20-I25) were analyzed separately.
RESULTS:
In the testing set, 1214 hard and 7201 soft CAD cases were documented during a mean follow-up of 11.2 years. The HR per standard deviation of the optimal PRS was 1.26 (95% CI:1.19-1.33) for hard CAD. Based on a traditional CAD risk prediction model containing only non-laboratory-based information, the addition of PRS for hard CAD increased Harrell's C index by 0.001 (-0.001 to 0.003) in women and 0.003 (0.001 to 0.005) in men. Among the different high-risk thresholds ranging from 1% to 10%, the highest categorical NRI was 3.2% (95% CI: 0.4-6.0%) at a high-risk threshold of 10.0% in women. The association of the PRS with soft CAD was much weaker than with hard CAD, leading to minimal or no improvement in the soft CAD model.
CONCLUSIONS
In this Chinese population sample, the current PRSs minimally changed risk discrimination and offered little improvement in risk stratification for soft CAD. Therefore, this may not be suitable for promoting genetic screening in the general Chinese population to improve CAD risk prediction.
Male
;
Humans
;
Female
;
Coronary Artery Disease/genetics*
;
Biological Specimen Banks
;
East Asian People
;
Risk Assessment/methods*
;
Genetic Predisposition to Disease/genetics*
;
Risk Factors
;
Genome-Wide Association Study
5.Breast Stem Cells.
Dongho CHOI ; Robert B CLARKE ; Min Hyuk LEE
Journal of Korean Breast Cancer Society 2004;7(1):1-7
Mammary gland development and function would not be possible without tissue-specific stem cells. The mammalian reproductive cycles of pregnancy-associated proliferation, lactational differentiation, apoptosis and remodelling following weaning may occur many times during a female's reproductive years. Such processes necessitate a population of tissue-specific stem cells that have a near unlimited capacity to generate the short-lived, differentiated breast cells. In contrast to the functional cells, breast stem cells must last throughout the life of an organism. Because of this longevity, stem cells may accumulate genetic alterations that eventually lead to cancer. Breast tumors contain a population with stem-cell characteristics. Current tumour therapy modalities target proliferative cells, and be successful in causing tumor regression. Targeting these tumor stem cells will be an important goal of future research.
Apoptosis
;
Breast Neoplasms
;
Breast*
;
Longevity
;
Mammary Glands, Human
;
Neoplastic Stem Cells
;
Stem Cells*
;
Weaning

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