Longitudinal Study Of Early Cardiovascular Outcomes And Risk Factors In Cancer Patients Receiving Anthracycline Chemotherapy In Tanzania

ObjectiveThe purpose of this study was to investigate the early cardiovascular outcomes and risk factors of cancer patients receiving anthracycline chemotherapy in Tanzania.To understand the early cardiovascular outcome of cancer patients receiving anthracycline chemotherapy drugs through a scope review,and to analyze the changes in early cardiovascular outcome indicators and the risk factors affecting early cardiovascular outcomes of cancer patients based on longitudinal studies.In order to understand the cardiovascular effects of receiving anthracycline chemotherapy drugs on cancer patients,timely identified and prevented cardiotoxicity in clinical patients after chemotherapy in advance.Taking targeted primary and secondary prevention measures to reduce adverse cardiovascular outcomes caused by anthracycline chemotherapy drugs and better ensure patient safety.MethodsThis study was a longitudinal study of early cardiovascular outcomes and their risk factors in cancer patients receiving anthracycline chemotherapy in Tanzania,which was divided into three parts.The first part was a review of the scope of early cardiovascular outcomes in cancer patients receiving anthracyclines.The scope of literature review was conducted,and the search strategy was as follows:The results included studies published through August 30,2018,Six Chinese and English databases,including Web of science,Pubmed,the Cochrane Library,CNKI,Wan Fang Database and VIP Database,were used.Specific Me SH(medical subject words)terms and keywords related to cardiotoxicity in cancer patients induced by anthracyclines chemotherapy drugs,combined terms related to heart disease,anthracyclines or drug therapy or chemotherapy were used,such as English search terms: "anthracycline," "doxorubicin," "epirubicin," "daunorubicin," "valrubicin," "blood pressure," "cardiomyopathy," "cardiac failure ",Chinese search words: "anthracyclines","doxorubicin","epirubicin","daunorubicin","valorubicin","blood pressure","heart failure","cardiomyosis",etc.,were cross-examined.Screening of studies on the effects of anthracyclines on early cardiovascular outcomes,inclusion and exclusion criteria: use Note Express,a literature management software,to download and merge all retrieved citations,review the study title and abstract,and then read the full article for inclusion.Minimum inclusion criteria: Studies that explored the effects of anthracyclines on early cardiovascular outcomes in cancer patients.The study design included randomized controlled trials,cohort studies,cross-sectional studies,and retrospective analyses.The study subjects were patients diagnosed with cancer and treated with anthracycline chemotherapy,regardless of age,gender,ethnicity,location,duration,or type of disease.Exclusion criteria: repeated literature,review,review articles,case reports,etc.,unable to view the abstract and full text of the literature;Literature reading and data and data extraction were conducted independently by two researchers according to the inclusion and exclusion criteria of literature.In case of any difference,the third reviewer reviewed the literature and reached a consensus after discussion.A selfdesigned standardized data extraction table was used to extract data,and thematic analysis of early cardiovascular outcomes was performed.The second part was an assessment of early cardiovascular outcomes in cancer patients receiving anthracyclines to explore differences in early cardiovascular outcome indicators before and 6 months after treatment.Cardiovascular data were collected from 430 new cancer patients who were newly diagnosed with cancer and were about to begin anthracycline chemotherapy at the Ocean Road Cancer Institute(ORCI)in Dar es Salaam,Tanzania,between January 2019 and September 2021,before beginning anthracycline treatment and six months after treatment.Include serum biochemical indicators(high density lipoprotein cholesterol,HDL-C;low density lipoprotein cholesterol,LDL-C;triglyceride,TG;cardiac troponin I,c Tn I);blood pressure(systolic blood pressure,SBP;diastolic blood pressure,DBP),and ECG information(heart rate,Bazett QT interval).The paired T-test and Chi-square test were used to compare baseline and early cardiovascular outcomes at 6 months using SPSS 26.0.P < 0.05 was considered statistically significant.The third part was an analysis of risk factors for changes in early cardiovascular outcomes in cancer patients receiving anthracyclines.A total of 430 new cancer patients who were newly diagnosed with cancer and were about to begin anthracycline chemotherapy at the ORCI in Dares Salaam,Tanzania,between January 2019 and September 2021,Patient demographic information(age,sex,marital status,occupation,education,type of cancer,any drugs used),cardiovascular risk factors(diabetes,history of high blood pressure,and history of other cardiovascular diseases,alcohol,diet,physical activity,smoking,and current dietary habits)were collected before beginning anthracycline treatment.Cardiovascular data were collected before treatment and 6 months after treatment(same as part2).SPSS 26.0 was used to analyze the cardiovascular risk factors of patients with anthracycline chemotherapy by single factor analysis using T-test,analysis of variance and rank sum test.Multivariate analysis of cardiovascular disease risk factors in cancer patients receiving anthracycline chemotherapy was performed using a linear mixing model(linear mixed model,LMM).Results1.Results of the Scoping ReviewA total of 8051 literature were retrieved from both Chinese and English databases,all of which were imported into Note Express software.6797 literature were obtained after excluding duplicate literature,236 literature were obtained after reading titles and abstracts,and review,animal experiments and other literature were excluded.14 literature were finally included after reading the full text and sifting the literature.There are 10 articles in English and 4 in Chinese.Subject analysis was carried out on the data and information,and basic information related to the research question was extracted from 14 literature,including author,year,title,DOI number,country,research type,research object,outcome index measurement tool,outcome index and results.A total of 22 indicators related to three categories of early cardiovascular outcomes were summarized as follows: Biochemical indicators(c Tn I,B-type natriuretic peptide(BNP),NT-pro BNP,ST2,lipids(TC,TG,HDL-C,LDL-C,Apo A-1,Apo-B),myocardial ischemia),Blood pressure related indicators(blood pressure,diastolic dysfunction(DD),left ventricular ejection fraction(LVEF)),ECG information(heart rate/rhythm,ST-T,QRS,conduction disorders,congestive heart failure,cardiotoxicity),etc.Nine articles reported the effects of anthracyclines on serum troponin,BNP and lipids(TC,TG,HDL-C,LDL-C,Apo-B and Apo-A1)in cancer patients.The results of the seven-article study showed that the use of anthracycline chemotherapy drugs may lead to changes in blood pressure,LVEF,and DD.Eight articles showed that the use of anthracyclines resulted in cardiotoxicity in patients,including arrhythmias,heart rate variability,myocardial ischemia,decreased QRS voltage,ST-T changes,prolonged QTc interval,conduction disorders,and congestive heart failure.2.Results of comparison of early cardiovascular outcome measures before and after treatmentPatients’ cardiovascular data were collected before beginning anthracycline treatment and six months after treatment.The questionnaire was adapted from the World Health Organization(World Health Organization,WHO)and modified to fit the objectives of the study.A total of 11,188 newly diagnosed cancer patients were obtained from January2019 to September 2021,of which 6,944 patients received anthracyclinebased chemotherapy.After routine laboratory examination and screening of inclusion criteria,only 1029 patients qualified for the study,89 patients who did not agree to participate in the study were excluded,and 34 patients who did not complete the treatment cycle were excluded.Finally,systematic sampling was carried out,with 2 participants at intervals taking samples successively until enough sample size was drawn.A total of 430 cases were eventually included.Comparison of SBP before and after treatment,SBP increased after treatment(t=5.200,P <0.001);comparing DBP before and after treatment,DBP increased after treatment(t=8.259,P <0.001).Comparison of the average levels of biochemical indicators before and after treatment,HDLC decreased after treatment(t=3.437,P=0.001);both TG and c Tn I rose after treatment(Z=-4.512,P <0.001;t=4.570,P <0.001);there was no significant difference in LDL-C and cholesterol before and after treatment(P> 0.05).Comparison of the mean ECG levels before and after treatment,RR(ms)decreased after treatment(t=3.131,P=0.002);QT(ms),QTc(ms),and heart rate(HR)all increased after treatment(t=1.999,P=0.046;t=4.797,P <0.001;t=3.859,P <0.001).3.Results of risk factor analysis of changes in early cardiovascular outcomes in cancer patients receiving anthracycline chemotherapyThe influence of CVDs risk factor on the clinical,biochemical,and electrophysiological outcomes of anthracycline chemotherapy was collected before beginning treatment.These risk factors include: physical inactivity,smoking,dyslipidemia,diabetes,stress,gout,periodontal disease,family history,alcohol consumption,high blood pressure,obesity,age and gender.A total of 430 patients were included in the study.Risk factors for cardiovascular disease were depression(42.3%),insufficient physical activity(37.9%),BMI over 30(30%),insufficient fruit intake(27%),lack of vegetables in the diet(19%),heavy drinking(11.4%),smoking(8.6%),history of high blood pressure(7.9%),family history of cardiovascular disease(6%),men aged 55(5.6%),diabetes(5.1%),and women(4.5%)aged 65 or older.Univariate analysis showed BMI and the change of DBP before and after treatment with or without a history of depression were statistically significant(P<0.05),suggesting that BMI and a history of depression may be risk factors for changes in DBP.The changes of SBP before and after treatment were statistically significant in marital status,BMI,second-hand smoke,anthracyclines,and types of physical activity(P<0.05)which showed that marital status,BMI,secondhand smoke,anthracycline treatment period,and type of physical activity may be risk factors for changes in SBP.HDL-C changes before and after treatment showed statistically significant differences in BMI and blood pressure history(P<0.05).This suggests that BMI and blood pressure history may be risk factors for HDL-C changes.The change of LDL-C before and after treatment showed that the difference of LDL-C between different genders before and after treatment was statistically significant(P < 0.05),suggesting that gender may be a risk factor for LDL-C change.The change of triglyceride before and after treatment showed that the change of triglyceride before and after treatment had a statistically significant difference in BMI(P<0.05).BMI may be a risk factor for triglyceride change.The change of troponin before and after treatment showed that the change of cardiac troponin I before and after treatment had a statistically significant difference in the history of hypertension(P < 0.05).This suggests that a history of hypertension may be a risk factor for changes in cardiac troponin I.Heart rate change before and after treatment showed that there were statistically significant differences in different BMI,exercise intensity,and exercise categories(P < 0.05),indicating that different BMI,exercise intensity,and exercise types may be risk factors for heart rate change.The changes of Bazett QT interval before and after treatment showed statistically significant differences in gender and fruit intake(P<0.05).The results suggest that different sex and fruit intake may be risk factors for Bazett QT interphase change.Changes in early cardiovascular outcomes in patients with new cancers induced by anthracyclines before and after treatment were used as dependent variables,and risk factors such as gender,age,and marital status were used as covariates.A linear mixed model was used for analysis to identify risk factors that might contribute to changes in early cardiovascular outcome indicators in cancer patients receiving anthracyclines.The results showed that gender and diabetes mellitus were risk factors for changes in DBP(P<0.05).Sex,marital status,education level,cancer type,BMI,and diabetes history were risk factors for changes in SBP(P<0.05).Marital status,educational level,and smoking history were risk factors for changes in HDL-C(P<0.05).Education level,income occupation,alcohol consumption history,physical activity intensity,history of diabetes mellitus diabetes,family history of cardiovascular disease,fruit intake,and fruit diet were risk factors for changes in LDL-C(P<0.05).Education,smoking history,BMI,diabetes history,and diabetes were risk factors for triglyceride changes(P <0.05).Type of cancer,history of alcohol,history of diabetes,family history of diabetes cardiovascular,vegetable intake plant diet were risk factors for changes in cardiac troponin I(P<0.05).Education,BMI,history of diabetes,and diabetes were risk factors for heart rate variation(P<0.05).Marital status,education level,cancer type,age,and secondhand smoke were the risk factors for the Bazett QT interval change(P<0.05).ConclusionCardiotoxicity is a common complication of chemotherapy with anthracyclines.In this study,cancer patients in Tanzania who received anthracyclines showed changes in early cardiovascular outcomes,including blood pressure,serum biochemical indices,and electrophysiological ECG indices.Risk factors for early cardiovascular outcomes in cancer patients who received anthracyclines were type of cancer,BMI,diabetes,high blood pressure,and history of other cardiovascular diseases,alcohol,diet,physical activity,smoking,and current dietary habits.