Circulating Stem/Progenitor Cells as Prognostic Biomarkers in Macro- and Microvascular Disease: A Narrative Review of Prospective Observational Studies

2018 ◽  
Vol 25 (35) ◽  
pp. 4507-4517 ◽  
Author(s):  
Mauro Rigato ◽  
Gian Paolo Fadini

Background: Circulating progenitor cells (CPCs) and endothelial progenitor cells (EPCs) are immature cells involved in vascular repair and related to many aspects of macro and microvascular disease. <p> Objective: We aimed to review studies reporting the prognostic role of CPCs/EPCs measurement on development of cardiovascular disease and microangiopathy. <p> Methods and Results: We reviewed the English language literature for prospective observational studies reporting the future development of cardiovascular disease or microangiopathy in patients having a baseline determination of CPCs/EPCs. We retrieved 34 studied reporting on cardiovascular outcomes and 2 studies reporting on microvascular outcomes. Overall, a reduced baseline level of CPCs/EPCs was associated with a significant increased risk of cardiovascular events, all-cause death, and onset/progression of microangiopathy. The most predictive phenotypes were CD34+ and CD34+CD133+. The main limitation was related to the high heterogeneity among studies in terms of patient characteristics and cell phenotypes. <p> Conclusion: The present review shows that a reduced level of circulating progenitor cells is a risk factor for the development of future cardiovascular events and death. In addition, low CPCs/EPCs levels predict the onset or worsening of microalbuminuria and retinopathy in diabetic patients.

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Lance S Longmore ◽  
Kimberly J Reid ◽  
Mikhail Kosiborod ◽  
Frederick A Masoudi ◽  
Verna Welch ◽  
...  

While diabetes is known to be associated with increased mortality after MI, whether these differences in outcome are due to patient characteristics, treatment, or other biological factors is unknown. We analyzed a contemporary cohort of MI survivors to comprehensively adjust for demographics, comorbidities, psychosocial, health status, clinical and treatment factors to determine if residual disparities in outcomes exist. We studied 2481 hospital survivors of MI in the prospective, 19-center PREMIER study (29% with diabetes). Multivariable models with sequential adjustment were employed to identify the extent to which variation in a wide range of patient characteristics (Figure ) accounted for differences in 3-year mortality in patients with and without diabetes. Unadjusted mortality was more than 2.5-fold greater for patients with diabetes (HR 2.55, 95% CI 2.08–3.14). Mortality was most attenuated by diabetes-related comorbidities (Figure ). The fully-adjusted model identified a significant, albeit attenuated, excess 3-year mortality among patients with diabetes (HR 1.57, 95% CI 1.22–1.99). Patients with diabetes experience a substantially increased risk for 3-year mortality after MI, even after accounting for a wide range of patient and treatment characteristics. This suggests that unmeasured, biologic variables associated with diabetes may mediate this difference. Further inquiry into the pathogenesis of diabetic cardiovascular disease is needed to identify new opportunities to improve the prognosis of patients with diabetes.


2016 ◽  
Vol 118 (12) ◽  
pp. 1930-1939 ◽  
Author(s):  
Mauro Rigato ◽  
Angelo Avogaro ◽  
Gian Paolo Fadini

Rationale: Circulating progenitor cells (CPCs), including endothelial progenitor cells (EPCs) are biologically related to many aspects of cardiovascular disease, as they promote angiogenesis and vascular repair. Objective: We herein aimed to meta-analyze studies reporting the prognostic role of the CPC/EPC measure on cardiovascular outcomes and death. Methods and Results: We screened the English-language literature for longitudinal studies reporting the association between baseline CPC/EPC levels, future cardiovascular events, and death. We retrieved 28 studies, 21 of which contained poolable data and entered the meta-analysis, for a total of 4155 patients, mostly with a high baseline cardiovascular risk. Sixty percent of the studies met at least 11 of 16 items of quality assessment. Overall, reduced CPC/EPC levels were associated with a ≈2-fold increased risk of future cardiovascular events and cardiovascular death. The most predictive phenotype was CD34 + CD133 + : low versus high levels predicted cardiovascular events, restenosis after endovascular intervention, cardiovascular death, and all-cause mortality. Heterogeneity among studies and according to the CPC/EPC phenotype was generally high. Excluding studies for which the risk estimate had to be extrapolated or limiting the analyses to higher quality studies still indicated a significant risk for future cardiovascular events and death in patients with low versus high progenitor cell counts. Conclusions: This meta-analysis shows that a reduction in the levels of circulating cells putatively provided with vasculoregenerative properties represents a risk factor for adverse cardiovascular outcomes and death.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaojing Chen ◽  
Per-Olof Hansson ◽  
Erik Thunström ◽  
Zacharias Mandalenakis ◽  
Kenneth Caidahl ◽  
...  

AbstractThe QRS complex has been shown to be a prognostic marker in coronary artery disease. However, the changes in QRS duration over time, and its predictive value for cardiovascular disease in the general population is poorly studied. So we aimed to explore if increased QRS duration from the age of 50–60 is associated with increased risk of major cardiovascular events during a further follow-up to age 71. A random population sample of 798 men born in 1943 were examined in 1993 at 50 years of age, and re-examined in 2003 at age 60 and 2014 at age 71. Participants who developed cardiovascular disease before the re-examination in 2003 (n = 86) or missing value of QRS duration in 2003 (n = 127) were excluded. ΔQRS was defined as increase in QRS duration from age 50 to 60. Participants were divided into three groups: group 1: ΔQRS < 4 ms, group 2: 4 ms ≤ ΔQRS < 8 ms, group 3: ΔQRS ≥ 8 ms. Endpoints were major cardiovascular events. And we found compared with men in group 1 (ΔQRS < 4 ms), men with ΔQRS ≥ 8 ms had a 56% increased risk of MACE during follow-up to 71 years of age after adjusted for BMI, systolic blood pressure, smoking, hyperlipidemia, diabetes and heart rate in a multivariable Cox regression analysis (HR 1.56, 95% CI:1.07–2.27, P = 0.022). In conclusion, in this longitudinal follow-up over a decade QRS duration increased in almost two out of three men between age 50 and 60 and the increased QRS duration in middle age is an independent predictor of major cardiovascular events.


2002 ◽  
Vol 2 (1_suppl) ◽  
pp. S4-S8
Author(s):  
Erland Erdmann

Diabetes is a common risk factor for cardiovascular disease. Coronary heart disease and left ventricular dysfunction are more common in diabetic patients than in non-diabetic patients, and diabetic patients benefit less from revascularisation procedures. This increased risk can only partly be explained by the adverse effects of diabetes on established risk factors; hence, a substantial part of the excess risk must be attributable to direct effects of hyperglycaemia and diabetes. In type 2 diabetes, hyperinsulinaemia, insulin resistance and hyperglycaemia have a number of potential adverse effects, including effects on endothelial function and coagulation. Risk factor modification has been shown to reduce the occurrence of cardiovascular events in patients with diabetes; indeed, diabetic patients appear to benefit more in absolute terms than non-diabetic patients. There is thus a strong case for intensive treatment of risk factors, including insulin resistance and hyperglycaemia, in patients with type 2 diabetes.


2020 ◽  
Vol 11 ◽  
Author(s):  
Ha Young Jang ◽  
Jae Hyun Kim ◽  
Yun-Kyoung Song ◽  
Ju-Young Shin ◽  
Hae-Young Lee ◽  
...  

Aims: Conflicting data exist on whether an association exists between antidepressants and the risk of major adverse cardiovascular events (MACEs) in patients with depression. This may be due to the use of various study designs and residual or unmeasured confounding. We aimed to assess the association between antidepressant use and the risk of MACEs while considering various covariates, including severity of depression and the cardiovascular disease (CVD) risk score.Methods: Patients newly diagnosed with depression with no history of ischemic heart disease and stroke were followed-up from 2009 to 2015. We conducted Cox proportional hazard regression analysis to estimate hazard ratios (HRs) for each antidepressant for MACE risk.Result: We followed-up (median, 4.4 years) 31,830 matched patients with depression (15,915 antidepressant users and 15,915 non-users). In most patients (98.7%), low-dose tricyclic antidepressants (TCAs) were related with a significantly increased risk of MACEs [adjusted HR = 1.20, 95% confidence interval (CI) = 1.03–1.40]. Duration response relationship showed a gradually increasing HR from 1.15 (95% CI = 0.98–1.33; &lt;30 days of use) to 1.84 (95% CI = 1.35–2.51; ≥365 days of use) (p for trend &lt;0.01). High Korean atherosclerotic CVD risk score (≥7.5%) or unfavorable lifestyle factors (smoking, alcohol intake, and exercise) were significantly associated with MACEs.Conclusion: Even at low doses, TCA use was associated with MACEs during primary prevention. Longer duration of TCA use correlated with higher HR. Careful monitoring is needed with TCA use in patients with no known CVD history.


Author(s):  
Marco Righetti

AbstractIn Italy, the mortality rate of hemodialysis patients is approximately 14% per year. Cardiovascular disease is the most important cause of morbidity and mortality in hemodialysis patients. High plasma homocysteine levels are commonly detected in these patients, but hyperhomocysteinemia and cardiovascular mortality are not always strictly correlated. The Dialysis Outcomes and Practice Pattern Study (DOPPS) showed a direct association between regular use of water-soluble vitamins and lower cardiovascular mortality. We recently performed a long-term prospective trial to study the effects of folic acid therapy on cardiovascular events in hemodialysis patients. We observed not only a lower rate of combined cardiovascular events in patients treated with folate, but also a direct correlation between hyperhomocysteinemia and cardiovascular morbidity. On the contrary, the distribution of deaths was similar in treated and untreated patients, because, almost certainly, sudden death is not always due to atherosclerotic events, and non-cardiovascular deaths, such as cachexia, septicemia and malignancy were characterized by low levels of homocysteine, which may be, in addition, a nutritional index similar to albumin and protein catabolic rate. As it is known that diabetic hemodialysis patients have a higher mortality rate, but lower homocysteine levels as compared to non-diabetic patients, we performed an equal allocation of diabetic patients in treated and untreated groups. We observed a similar homocysteine reduction rate in diabetic patients as compared to non-diabetic patients, and a trend towards a lower rate of composite cardiovascular events in treated diabetic patients as compared to untreated diabetic patients. To summarize, the strong relationship between homocysteine and nutritional, inflammatory markers may hide its association with cardiovascular disease. Homocysteine-lowering vitamin B therapy may lower cardiovascular events in dialysis patients. It is mandatory to perform large prospective trials to confirm our results.Clin Chem Lab Med 2007;45:1586–9.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Jie Wang ◽  
Yangjing Xue ◽  
Saroj Thapa ◽  
Luping Wang ◽  
Jifei Tang ◽  
...  

Data on the association between age-related macular degeneration (AMD) and cardiovascular disease and mortality are conflicting. The purpose of this report is to conduct a systematic review to better understand the role of AMD as a risk factor for CVD events and mortality. We searched Medline (Ovid) and Embase (Ovid) for trials published from 1980 to 2015. We included 20 cohort studies that reported relative risks with 95% confidence intervals for the association of AMD and cardiovascular events and mortality, involving 29,964,334 participants. In a random-effects model, the adjusted RR (95% confidence interval [CI]) associated with AMD was 1.08 (1.00–1.117) for all-cause mortality (8 studies) and 1.18 (0.98–1.43) for cardiovascular disease mortality (5 studies). The pooled RR (95% CI) was 1.17 (0.94–1.45) for coronary heart disease (CHD; 3 studies) and 1.13 (0.93–1.36) for stroke (8 studies). Findings from this systematic review support that AMD is associated with increased risk of all-cause mortality. The evidence that AMD predicts incident CVD events or CVD mortality remains inclusive and warrants further study in the future.


Lupus ◽  
2017 ◽  
Vol 26 (14) ◽  
pp. 1463-1472 ◽  
Author(s):  
S Fasano ◽  
D P Margiotta ◽  
L Navarini ◽  
L Pierro ◽  
I Pantano ◽  
...  

Background Systemic lupus erythematosus is associated with an increased risk of cardiovascular disease. Low-dose aspirin, hydroxychloroquine and statins have been suggested to play a prophylactic role of cardiovascular events. This study is devoted to reviewing the literature on the topic and assessing the effects of these drugs in preventing a first cardiovascular event in a two-centre Italian series. Methods A PubMed search on cardiovascular prevention in systemic lupus erythematosus was performed. Moreover, systemic lupus erythematosus patients admitted to two centres from 2000–2015, who at admission had not experienced any cardiovascular event, were investigated. Aspirin, hydroxychloroquine and statin use, and the occurrence of any cardiovascular event, were recorded at each visit. Kaplan-Meier and Cox regression analyses were performed to evaluate the role of traditional, disease-related cardiovascular risk factors and of each of the three drugs in the occurrence of new cardiovascular events. Results The literature search produced conflicting results. Two hundred and ninety-one systemic lupus erythematosus patients were included in the study and followed for a median of eight years. During follow-up, 16 cardiovascular events occurred. At multivariate analysis, taking aspirin (hazard ratio: 0.24) and hydroxychloroquine for more than five years (hazard ratio: 0.27) reduced, while antiphospholipid antibody positivity (hazard ratio: 4.32) increased, the risk of a first cardiovascular event. No effect of statins emerged. Conclusion Our study confirms an additive role of aspirin and hydroxychloroquine in the primary prophylaxis of cardiovascular events in Italian patients with systemic lupus erythematosus. The lack of any detected effect in previous reports may depend on the design of studies and their short follow-up period.


2021 ◽  
Author(s):  
Rose Gubitosi-Klug ◽  
Xiaoyu Gao ◽  
Rodica Pop-Busui ◽  
Ian H de Boer ◽  
Neill White ◽  
...  

<b>Objective:</b> We examined whether the presence of microvascular complications was associated with increased subsequent risk of cardiovascular disease (CVD) among participants with type 1 diabetes in the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study followed for over 35 years. <p><b>Research Design and Methods:</b> Standardized longitudinal data collection included: 1) stereoscopic seven-field retinal fundus photography centrally-graded for retinopathy stage and clinically significant macular edema; 2) urinary albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR); 3) cardiovascular autonomic neuropathy (CAN) reflex testing; and 4) adjudicated CVD events, including death from cardiovascular disease, nonfatal myocardial infarction, stroke, subclinical myocardial infarction on ECG, confirmed angina, or coronary artery revascularization. Cox proportional hazard models assessed the association of microvascular complications with subsequent risk of CVD. </p> <p><b>Results:</b> 239 participants developed CVD, including 120 participants who suffered major adverse cardiovascular events (MACE) defined as non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. The presence of microvascular disease (diabetic retinopathy, kidney disease, or CAN) was associated with increased risk of subsequent CVD and MACE (hazard ratios 1.86 to 3.18 and 2.09 to 3.63, respectively); associations that remained significant after adjusting for age and HbA1c. After adjustment for traditional CVD risk factors, however, only sustained AER≥30 mg/24hr occurring alone and/or with eGFR<60 ml/min/1.73m, and the presence of both retinal and kidney disease remained associated with CVD. </p> <p><b>Conclusions:</b> Advanced microvascular disease, especially moderate to severe albuminuria or eGFR<60 ml/min/1.73m<sup>2</sup>, conveyed an increased risk of subsequent cardiovascular disease in the DCCT/EDIC cohort. </p>


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