Cardiovascular Disease Prevention in the Era of Personalized Medicine

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Mechanisms of Diseases".

Deadline for manuscript submissions: closed (22 February 2022) | Viewed by 54948

Special Issue Editor

Special Issue Information

Dear colleagues,

Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Prevention of CVD is based on the management of cardiovascular risk factors, including hypertension, dyslipidemia, diabetes mellitus, obesity, and smoking. Antiplatelet and anticoagulant treatment is also needed in certain subgroups. With the introduction of several novel pharmacological agents, personalized decisions can be made to optimize the safety and efficacy of the treatment of these risk factors. In this Special Issue, the management of the major modifiable cardiovascular risk factors is discussed. Given the multitude of therapeutic options, an evidence-based strategy is essential to reducing cardiovascular morbidity and mortality, particularly in high-risk patients with multiple comorbidities.

Dr. Konstantinos Tziomalos
Guest Editor

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Published Papers (19 papers)

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8 pages, 263 KiB  
Article
Evaluation of Subclinical Vascular Disease in Diabetic Kidney Disease: A Tool for Personalization of Management of a High-Risk Population
by Christodoula Kourtidou, Vasileios Rafailidis, Garyfallia Varouktsi, Efthimios Kanakis, Vassilios Liakopoulos, Timoleon-Achilleas Vyzantiadis, Maria Stangou, Smaragdi Marinaki and Konstantinos Tziomalos
J. Pers. Med. 2022, 12(7), 1139; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12071139 - 14 Jul 2022
Cited by 5 | Viewed by 1336
Abstract
Background: Patients with diabetic kidney disease (DKD) are at increased risk for cardiovascular events but traditional risk factors do not fully explain this association. Evaluation of subclinical vascular disease might improve risk stratification and management of these patients. The aim of the study [...] Read more.
Background: Patients with diabetic kidney disease (DKD) are at increased risk for cardiovascular events but traditional risk factors do not fully explain this association. Evaluation of subclinical vascular disease might improve risk stratification and management of these patients. The aim of the study was to compare the prevalence of markers of arterial stiffness, carotid atherosclerosis and peripheral arterial disease between patients with DKD and patients with type 2 diabetes mellitus (T2DM) and preserved kidney function. Methods: We prospectively enrolled patients with DKD and age- and gender-matched patients with T2DM but without DKD (estimated glomerular filtration rate < and ≥60 mL/min/1.73 m2, respectively). The presence of arterial stiffness was evaluated by measuring pulse wave velocity (PWV), augmentation index (AIx), AIx adjusted to a heart rate of 75 beats/min (AIx@75) and central systolic, diastolic, pulse and mean blood pressure. The presence of carotid atherosclerosis was evaluated by measuring carotid stenosis, carotid intima-media thickness and maximal plaque thickness. The presence of PAD was evaluated with the measurement of ankle-brachial index (ABI). Results: Forty patients with T2DM were included in the study (mean age 71.6 ± 8.9 years). The prevalence of cardiovascular risk factors was similar in patients with and without DKD. PWV was higher in the former (9.8 ± 5.5 and 6.6 ± 4.4 m/s, respectively; p < 0.05) and carotid stenosis of the left carotid artery was also greater in patients with DKD (36.5 ± 12.6 and 22.1 ± 17.2%, respectively; p < 0.05). Other markers of arterial stiffness and carotid atherosclerosis and ABI did not differ between patients with DKD and those without DKD. Conclusions: Patients with DKD appear to have more pronounced arterial stiffness and carotid atherosclerosis than patients with T2DM and preserved kidney function despite the similar prevalence of traditional cardiovascular risk factors in the two groups. Therefore, evaluating the presence of subclinical vascular disease in these patients could be a useful tool for the personalization of their management. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)
21 pages, 1771 KiB  
Article
Impact of the Genotype and Phenotype of CYP3A and P-gp on the Apixaban and Rivaroxaban Exposure in a Real-World Setting
by Camille Lenoir, Jean Terrier, Yvonne Gloor, Pauline Gosselin, Youssef Daali, Christophe Combescure, Jules Alexandre Desmeules, Caroline Flora Samer, Jean-Luc Reny and Victoria Rollason
J. Pers. Med. 2022, 12(4), 526; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12040526 - 24 Mar 2022
Cited by 12 | Viewed by 2788
Abstract
Apixaban and rivaroxaban are the two most prescribed direct factor Xa inhibitors. With the increased use of DOACs in real-world settings, safety and efficacy concerns have emerged, particularly regarding their concomitant use with other drugs. Increasing evidence highlights drug–drug interactions with CYP3A/P-gp modulators [...] Read more.
Apixaban and rivaroxaban are the two most prescribed direct factor Xa inhibitors. With the increased use of DOACs in real-world settings, safety and efficacy concerns have emerged, particularly regarding their concomitant use with other drugs. Increasing evidence highlights drug–drug interactions with CYP3A/P-gp modulators leading to adverse events. However, current recommendations for dose adjustment do not consider CYP3A/P-gp genotype and phenotype. We aimed to determine their impact on apixaban and rivaroxaban blood exposure. Three-hundred hospitalized patients were included. CYP3A and P-gp phenotypic activities were assessed by the metabolic ratio of midazolam and AUC0–6h of fexofenadine, respectively. Relevant CYP3A and ABCB1 genetic polymorphisms were also tested. Capillary blood samples collected at four time-points after apixaban or rivaroxaban administration allowed the calculation of pharmacokinetic parameters. According to the developed multivariable linear regression models, P-gp activity (p < 0.001) and creatinine clearance (CrCl) (p = 0.01) significantly affected apixaban AUC0–6h. P-gp activity (p < 0.001) also significantly impacted rivaroxaban AUC0–6h. The phenotypic switch (from normal to poor metabolizer) of P-gp led to an increase of apixaban and rivaroxaban AUC0–6h by 16% and 25%, respectively, equivalent to a decrease of 38 mL/min in CrCl according to the apixaban model. CYP3A phenotype and tested SNPs of CYP3A/P-gp had no significant impact. In conclusion, P-gp phenotypic activity, rather than known CYP3A/P-gp polymorphisms, could be relevant for dose adjustment. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)
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18 pages, 4041 KiB  
Article
Genetic Polymorphisms in a Familial Hypercholesterolemia Population from North-Eastern Europe
by Alexandra Maștaleru, Sabina Alexandra Cojocariu, Andra Oancea, Maria Magdalena Leon Constantin, Mihai Roca, Ioana Mădălina Zota, Irina Abdulan, Cristina Rusu, Roxana Popescu, Lucian Mihai Antoci, Cristian Gabriel Ciobanu, Alexandru Dan Costache, Elena Cojocaru and Florin Mitu
J. Pers. Med. 2022, 12(3), 429; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12030429 - 09 Mar 2022
Cited by 2 | Viewed by 2654
Abstract
(1) Background: Familial hypercholesterolemia (FH) is one of the most prevalent inherited metabolic disorders. The purpose of the study was to investigate the role in cardiovascular disease (CVD) of PAI-1, ACE, ApoB-100, MTHFR A1298C, and C677T. (2) Methods: [...] Read more.
(1) Background: Familial hypercholesterolemia (FH) is one of the most prevalent inherited metabolic disorders. The purpose of the study was to investigate the role in cardiovascular disease (CVD) of PAI-1, ACE, ApoB-100, MTHFR A1298C, and C677T. (2) Methods: From a group of 1499 patients, we included 52 patients diagnosed with FH phenotype and 17 patients in a control group. (3) Results: Most of the FH patients had multiple comorbidities compared to the control group, such as atherosclerosis (48.1% vs. 17.6%), atherosclerotic cardiovascular disease (ASCVD 32.7% vs. 11.8%), and metabolic syndrome (MetS, 40.4% vs. 11.8%). In total, 66.7% of the FH patients had PAI-1 4G/5G genotype and MetS. Between 4G/5G and 4G/4G, a statistically significant difference was observed (p = 0.013). FH patients with ApoB R3500Q polymorphism were correlated with ASCVD (p = 0.031). Both MTHFR C677T and A1298C polymorphisms had a significant correlation with gender, alcohol consumption, and smoking status. ACE polymorphism was associated with ATS in FH patients, statistically significant differences being observed between heterozygous and homozygous D genotype (p = 0.036) as well as between heterozygous and homozygous I genotype (p = 0.021). (4) Conclusions: A link between these polymorphisms was demonstrated in the FH group for ATS, ASCVD, and MetS. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)
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14 pages, 451 KiB  
Article
A Prospective Study of CPAP Therapy in Relation to Cardiovascular Outcome in a Cohort of Romanian Obstructive Sleep Apnea Patients
by Ioana Maria Chetan, Anca Diana Maierean, Bianca Domokos Gergely, Georgiana Cabau, Raluca Tomoaia, Ana Florica Chis, Adriana Albu, Mirela Anca Stoia, Stefan Cristian Vesa, Dan Blendea and Doina Adina Todea
J. Pers. Med. 2021, 11(10), 1001; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11101001 - 02 Oct 2021
Cited by 5 | Viewed by 2208
Abstract
Background: Despite efforts at treatment, obstructive sleep apnea (OSA) remains a major health problem, especially with increasing evidence showing an association with cardiovascular morbidity and mortality. The treatment of choice for OSA patients is Continuous Positive Airway Pressure (CPAP), which has been proven [...] Read more.
Background: Despite efforts at treatment, obstructive sleep apnea (OSA) remains a major health problem, especially with increasing evidence showing an association with cardiovascular morbidity and mortality. The treatment of choice for OSA patients is Continuous Positive Airway Pressure (CPAP), which has been proven in randomized controlled trials to be an effective therapy for this condition. The impact of CPAP on the cardiovascular pathology associated with OSA remains, however, unclear. Although the effect of CPAP has been previously studied in relation to cardiovascular outcome, follow-up of the treatment impact on cardiovascular risk factors at one year of therapy is lacking in a Romanian population. Thus, we aimed to evaluate the one-year effect of CPAP therapy on lipid profile, inflammatory state, blood pressure and cardiac function, assessed by echocardiography, on a cohort of Romanian OSA patients. Methods: We enrolled 163 participants and recorded their baseline demographic and clinical characteristics with a follow-up after 12 months. Inflammatory and cardiovascular risk factors were assessed at baseline and follow up. Results: Our results show that CPAP therapy leads to attenuation of cardiovascular risk factors including echocardiographic parameters, while having no effect on inflammatory markers. Conclusion: Treatment of OSA with CPAP proved to have beneficial effects on some of the cardiovascular risk factors while others remained unchanged, raising new questions for research into the treatment and management of OSA patients. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)
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10 pages, 779 KiB  
Article
Lower Lean Mass Is Associated with Greater Arterial Stiffness in Patients with Lower Extremity Artery Disease
by Viktoria Muster, Katharina Gütl, Gudrun Pregartner, Andrea Berghold, Leyla Schweiger, Philipp Jud, Marianne Brodmann and Gerald Seinost
J. Pers. Med. 2021, 11(9), 911; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11090911 - 13 Sep 2021
Cited by 2 | Viewed by 1663
Abstract
Background: Arterial stiffness is independently associated with lower extremity artery disease (LEAD). Although obesity is already known as an independent cardiovascular risk factor, it was found that, paradoxically, in patients diagnosed with cardiovascular disease, an increase in body mass index (BMI) was associated [...] Read more.
Background: Arterial stiffness is independently associated with lower extremity artery disease (LEAD). Although obesity is already known as an independent cardiovascular risk factor, it was found that, paradoxically, in patients diagnosed with cardiovascular disease, an increase in body mass index (BMI) was associated with a decrease in mortality. However, the underlying mechanism of this paradoxical association remain uncertain. In this study, we firstly hypothesize that arterial stiffness correlates with body mass; secondly, the underlying mechanism of the association for patients with LEAD is individual body composition, in particular, lean mass. Methods: The present study was performed as a single-center, prospective, observational analysis. A total of 412 patients with current or previously diagnosed LEAD (Rutherford Classification 2–4) were included, the cfPWV and AIx were measured as indices of arterial stiffness, and a body composition assessment was performed. Results: In male patients, there was a significantly negative correlation between the AIx and lean mass coefficient (p = 0.004, 95% CI: −0.28 (−0.48–0.09)). Conclusion: For patients with peripheral arterial disease, our data show that lower lean mass in male patients is associated with increased arterial stiffness as measured by the AIx. Therefore, progressive resistance training may be beneficial for the reduction in arterial stiffness in PAD patients in secondary prevention. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)
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16 pages, 897 KiB  
Article
Molecular Determination of mirRNA-126 rs4636297, Phosphoinositide-3-Kinase Regulatory Subunit 1-Gene Variability rs7713645, rs706713 (Tyr73Tyr), rs3730089 (Met326Ile) and Their Association with Susceptibility to T2D
by Rashid Mir, Imadeldin Elfaki, Faisel M. Abu Duhier, Maeidh A. Alotaibi, Adel Ibrahim AlAlawy, Jameel Barnawi, Abdullatif Taha Babakr, Mohammad Muzaffar Mir, Hyder Mirghani, Abdullah Hamadi and Pradeep Kumar Dabla
J. Pers. Med. 2021, 11(9), 861; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11090861 - 29 Aug 2021
Cited by 9 | Viewed by 2142
Abstract
Type 2 diabetes is a metabolic disease characterized by elevated blood sugar. It has serious complications and socioeconomic impact. The MicroRNAs are short single-stranded and non-coding RNA molecules. They regulate gene expression at the post-transcriptional levels. They are important for many physiological processes [...] Read more.
Type 2 diabetes is a metabolic disease characterized by elevated blood sugar. It has serious complications and socioeconomic impact. The MicroRNAs are short single-stranded and non-coding RNA molecules. They regulate gene expression at the post-transcriptional levels. They are important for many physiological processes including metabolism, growth, and others. The phosphoinositide 3-kinase (PI3K) is important for insulin signaling and glucose uptake. The genome wide association studies have identified the association of certain loci with diseases including T2D. In this study we have examined the association of miR126 rs4636297 and Phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) gene Variations rs7713645, rs706713 (Tyr73Tyr), and rs3730089 (Met326Ile) with T2D using the amplification refractory mutation system PCR. Results indicated that there was a significant different (p-value < 0.05) in the Mir126 rs4636297 genotypes distribution between cases and controls, and the minor allele of the rs4636297 was also associated with T2D with OR = 0.58, p-value < 0.05. In addition results showed that there were significant differences (p-value < 0.05) of rs4636297 genotype distribution of patients with normal and patient with abnormal lipid profile. Results also showed that the PIK3R1 rs7713645 and rs3730089 genotype distribution was significantly different between cases and controls with a p-values < 0.05. In addition, the minor allele of the rs7713645 and rs3730089 were associated with T2D with OR = 0.58, p-value < 0.05. We conclude that the Mir126 rs4636297 and PIK3R1 SNPs (rs7713645 and rs3730089) were associated with T2D. These results need verification in future studies with larger sample sizes and in different populations. Protein-protein interaction and enzyme assay studies are also required to uncover the effect of the SNPs on the PI3K regulatory subunit (PI3KR1) and PI3K catalytic activity. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)
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9 pages, 397 KiB  
Article
Improvement of Cognitive Function and Interleukin 1 Beta Serum Concentrations Following Cardiac Pacemaker Implantation in Patients with Symptomatic Bradycardia
by Alexandru Martis, Gabriel Gusetu, Gabriel Cismaru, Dumitru Zdrenghea, Daniel-Corneliu Leucuta and Dana Pop
J. Pers. Med. 2021, 11(8), 770; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11080770 - 05 Aug 2021
Cited by 4 | Viewed by 2137
Abstract
Background and aim: Bradyarrhythmias cause a low cerebral blood flow with secondary neuronal ischemia and cognitive dysfunction. This study aims to assess the effect of cardiac pacemaker implantation (PI) on the cognitive function and inflammatory markers (TNF alpha, IL1β). Material and method: We [...] Read more.
Background and aim: Bradyarrhythmias cause a low cerebral blood flow with secondary neuronal ischemia and cognitive dysfunction. This study aims to assess the effect of cardiac pacemaker implantation (PI) on the cognitive function and inflammatory markers (TNF alpha, IL1β). Material and method: We conducted a prospective observational study on a number of 31 patients with symptomatic bradyarrhythmias. We performed the cognitive function assessment by two tests (Mini-Mental State Examination and Trail Making Test A), cardiac output assessment (echocardiographic), and determination of IL 1β and TNF alpha serum concentrations before pacemaker implantation and after an average period of 42 days from pacemaker implantation.Results: After pacemaker implantation we observed an increase in the cardiac index by 0.71 L/min/m2 (p < 0.001) and a better scoring in cognitive performance; the mean MMSE score increased by two points (p < 0.001), and Trail Making Test A had an improvement of 16 s (p < 0.001). Regarding the inflammatory markers, a significant decrease in IL-1β with 8.6 pg/mL (p = 0.049) after pacemaker implantation was observed. Additionally, we found statistically significant correlations between IL1β and TNF alpha (positive correlation, p = 0.005), between the MMSE and cardiac index (p < 0.001), between the Trail Making Test and cardiac index (p = 0.001), and between the MMSE and Trail Making Test (p = 0.003). Conclusions: Our findings suggest that cardiac pacemaker implantation was associated with improved cognitive function—possibly related to an increased cardiac output and with adecreased serum IL1β concentration in subjects with symptomatic bradycardia. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)
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9 pages, 590 KiB  
Article
The Metabolic Score for Insulin Resistance (METS-IR) as a Predictor of Incident Ischemic Heart Disease: A Longitudinal Study among Korean without Diabetes
by Jihyun Yoon, Donghyuk Jung, Yongjae Lee and Byoungjin Park
J. Pers. Med. 2021, 11(8), 742; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11080742 - 28 Jul 2021
Cited by 37 | Viewed by 3823
Abstract
The metabolic score for insulin resistance (METS-IR) is a novel noninsulin-based marker for assessing the risk of insulin resistance and cardiometabolic risk. However, whether METS-IR is associated with incident ischemic heart disease (IHD) risk is not well known. Therefore, we aimed to investigate [...] Read more.
The metabolic score for insulin resistance (METS-IR) is a novel noninsulin-based marker for assessing the risk of insulin resistance and cardiometabolic risk. However, whether METS-IR is associated with incident ischemic heart disease (IHD) risk is not well known. Therefore, we aimed to investigate the longitudinal effect of METS-IR on incident IHD risk in a large cohort of Korean adults without diabetes. Data were assessed from 17,943 participants without diabetes from the Health Risk Assessment Study (HERAS) and Korea Health Insurance Review and Assessment (HIRA) data. The participants were divided into four groups according to METS-IR index quartiles: (ln ((2 × fasting plasma glucose) + triglyceride) × body mass index)/(ln (HDL-cholesterol)). We prospectively assessed hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD using multivariate Cox proportional hazard regression models over a 50-month period. During the follow-up period, 332 participants (1.9%) developed IHD. HRs of IHD for METS-IR quartiles 1–4 were 1.00, were 1.62 (95% CI 1.04–2.53), 1.87 (95% CI 1.20–2.91), and 2.11 (95% CI 1.35–3.30), respectively, after adjusting for potential confounding variables. A higher METS-IR precedes future IHD among Koreans without diabetes. Moreover, compared with metabolic syndrome, METS-IR had a better predictive value for IHD. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)
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17 pages, 278 KiB  
Article
Self-Reported Modifiable Risk Factors of Cardiovascular Disease among Seafarers: A Cross-Sectional Study of Prevalence and Clustering
by Getu Gamo Sagaro, Gopi Battineni, Marzio Di Canio and Francesco Amenta
J. Pers. Med. 2021, 11(6), 512; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11060512 - 04 Jun 2021
Cited by 10 | Viewed by 2143
Abstract
Background: Cardiovascular diseases (CVD) are the major cause of work-related mortality from diseases onboard ships in seafarers. CVD burden derives mainly from modifiable risk factors. To reduce the risk factors and the burden of CVD onboard ships in seafarers, it is important to [...] Read more.
Background: Cardiovascular diseases (CVD) are the major cause of work-related mortality from diseases onboard ships in seafarers. CVD burden derives mainly from modifiable risk factors. To reduce the risk factors and the burden of CVD onboard ships in seafarers, it is important to understand the up-to-date prevalence of modifiable risk factors. The primary purpose of this study was to assess the prevalence and clustering of self-reported modifiable CVD risk factors among seafarers. We have also explored the association between socio-demographic and occupational characteristics and reported modifiable CVD risk factor clustering. Materials and methods: A cross-sectional study was conducted among seafarers from November to December 2020 on board ships. In total, 8125 seafarers aged 18 to 70 were selected from 400 ships. Data were collected using a standardized and anonymous self-reported questionnaire. The prevalence value for categorical variables and mean differences for continuous variables were compared using chi-square and independent sample t-tests. Multinomial logistic regression models were performed to identify independent predictors for modifiable CVD risk factor clustering. Results: Out of a total of 8125 seafarers aged ≥18 years on selected vessels, 4648 seafarers volunteered to participate in the survey, with a response rate of 57.2%. Out of 4318 participants included in analysis, 44.7% and 55.3% were officers and non-officers, respectively. The prevalence of reported hypertension, diabetes, current smoking and overweight or obesity were 20.8%, 8.5%, 32.5%, and 44.7%, respectively. Overall, 40%, 20.9%, 6% and 1.3% of the study participants respectively had one, two, three and four modifiable CVD risk factors. Older age (51+ years) (odds ratio (OR): 3.92, 95% confidence interval (CI): 2.44–6.29), being non-officers (OR: 1.36, 95% CI: 1.09–1.70), job duration (10–20 years) (OR: 2.73, 95% CI: 2.09–3.57), job duration (21+ years) (OR: 2.60, 95% CI: 1.79–3.78), working 57–70 h per week (OR: 2.03, 95% CI: 1.65–2.49) and working 71+ h per week (OR: 3.08, 95% CI: 2.42–3.92) were independent predictors for at least two self-reported modifiable CVD risk factor clustering. Conclusion: The results of our study demonstrate that more than four in six (68.5%) seafarers aged between 19 and 70 years have at least one of the modifiable CVD risk factors. Therefore, CVD prevention and modifiable risk factors reduction strategies targeting high-risk groups should be designed and implemented on board ships. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)
12 pages, 1632 KiB  
Article
MiR-126-3p and MiR-223-3p as Biomarkers for Prediction of Thrombotic Risk in Patients with Acute Myocardial Infarction and Primary Angioplasty
by Milan Hromadka, Zuzana Motovska, Ota Hlinomaz, Petr Kala, Frantisek Tousek, Jiri Jarkovsky, Marketa Beranova, Pavel Jansky, Michal Svoboda, Iveta Krepelkova, Richard Rokyta, Petr Widimsky and Michal Karpisek
J. Pers. Med. 2021, 11(6), 508; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11060508 - 04 Jun 2021
Cited by 18 | Viewed by 2522
Abstract
Aim. This study was designed to evaluate the relationship between microRNAs (miRNAs), miR-126-3p and miR-223-3p, as new biomarkers of platelet activation, and predicting recurrent thrombotic events after acute myocardial infarction (AMI). Methods and Results. The analysis included 598 patients randomized in the PRAGUE-18 [...] Read more.
Aim. This study was designed to evaluate the relationship between microRNAs (miRNAs), miR-126-3p and miR-223-3p, as new biomarkers of platelet activation, and predicting recurrent thrombotic events after acute myocardial infarction (AMI). Methods and Results. The analysis included 598 patients randomized in the PRAGUE-18 study (ticagrelor vs. prasugrel in AMI). The measurements of miRNAs were performed by using a novel miRNA immunoassay method. The association of miRNAs with the occurrence of the ischemic endpoint (EP) (cardiovascular death, nonfatal MI, or stroke) and bleeding were analyzed. The miR-223-3p level was significantly related to an increased risk of occurrence of the ischemic EP within 30 days (odds ratio (OR) = 15.74, 95% confidence interval (CI): 2.07–119.93, p = 0.008) and one year (OR = 3.18, 95% CI: 1.40–7.19, p = 0.006), respectively. The miR-126-3p to miR-223-3p ratio was related to a decreased risk of occurrence of EP within 30 days (OR = 0.14, 95% CI: 0.03–0.61, p = 0.009) and one year (OR = 0.37, 95% CI: 0.17–0.82, p = 0.014), respectively. MiRNAs were identified as independent predictors of EP even after adjustment for confounding clinical predictors. Adding miR-223-3p and miR-126-3p to miR-223-3p ratios as predictors into the model calculating the ischemic risk significantly increased the predictive accuracy for combined ischemic EP within one year more than using only clinical ischemic risk parameters. No associations between miRNAs and bleeding complications were identified. Conclusion. The miR-223-3p and the miR-126-3p are promising independent predictors of thrombotic events and can be used for ischemic risk stratification after AMI. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)
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10 pages, 1299 KiB  
Article
Prevalence of Pulmonary Hypertension in an Unselected Community-Based Population: A Retrospective Echocardiographic Study—RES-PH Study
by Egidio Imbalzano, Marco Vatrano, Alberto Lo Gullo, Luana Orlando, Alberto Mazza, Vincenzo Antonio Ciconte, Vincenzo Russo, Clemente Giuffrida, Pierpaolo Di Micco, Antonio Giovanni Versace, Giuseppe Mandraffino and Giovanni Squadrito
J. Pers. Med. 2021, 11(6), 489; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11060489 - 31 May 2021
Cited by 2 | Viewed by 3556
Abstract
Introduction. The actual prevalence of pulmonary hypertension (PH) in Italy is unknown. Echocardiography is useful in the screening of patients with suspected PH by estimation of the pulmonary artery systolic pressure (PASP) from the regurgitant tricuspid flow velocity evaluation, according to the simplified [...] Read more.
Introduction. The actual prevalence of pulmonary hypertension (PH) in Italy is unknown. Echocardiography is useful in the screening of patients with suspected PH by estimation of the pulmonary artery systolic pressure (PASP) from the regurgitant tricuspid flow velocity evaluation, according to the simplified Bernoulli equation. Objectives. We aimed to evaluate the frequency of suspected PH among unselected patients. Methods. We conducted a retrospective cross-sectional database search of 7005 patients, who underwent echocardiography, to estimate the prevalence of PH, between January 2013 and December 2014. Medical and echocardiographic data were collected from a stratified etiological group of PH, using criteria of the European Society of Cardiology classifications. Results. The mean age of the study population was 57.1 ± 20.5 years, of which 55.3% were male. The prevalence of intermediate probability of PH was 8.6%, with nearly equal distribution between men and women (51.3 vs. 48.7%; p = 0.873). The prevalence of high probability of PH was 4.3%, with slightly but not significant higher prevalence in female patients (43.2 vs. 56.8%; p = 0.671). PH is predominant in patients with chronic obstructive pulmonary disease (COPD) or left ventricle (LV) systolic dysfunction and related with age. PASP was significantly linked with left atrial increase and left ventricular ejection fraction. In addition, an increased PASP was related to an enlargement of the right heart chamber. Conclusions. PH has a frequency of 4.3% in our unselected population, but the prevalence may be more relevant in specific subgroups. A larger epidemiological registry could be an adequate strategy to increase quality control and identify weak points in the evaluation and treatment of these patients. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)
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17 pages, 2952 KiB  
Article
Association between HOTAIR lncRNA Polymorphisms and Coronary Artery Disease Susceptibility
by In-Jai Kim, Jeong-Yong Lee, Hyeon-Woo Park, Han-Sung Park, Eun-Ju Ko, Jung-Hoon Sung and Nam-Keun Kim
J. Pers. Med. 2021, 11(5), 375; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11050375 - 04 May 2021
Cited by 8 | Viewed by 2195
Abstract
Coronary artery disease (CAD), one of the most frequent causes of mortality, is the most common type of cardiovascular disease. This condition is characterized by the accumulation of plaques in the coronary artery, leading to blockage of blood flow to the heart. The [...] Read more.
Coronary artery disease (CAD), one of the most frequent causes of mortality, is the most common type of cardiovascular disease. This condition is characterized by the accumulation of plaques in the coronary artery, leading to blockage of blood flow to the heart. The main symptom of CAD is chest pain caused by blockage of the coronary artery and shortness of breath. HOX transcript antisense RNA gene (HOTAIR) is a long non-coding RNA which is well-known as an oncogene involved in various cancers, such as lung, breast, colorectal, and gastric cancer. We selected six single nucleotide polymorphisms, rs4759314 A>G, rs1899663 G>T, rs920778 T>C, rs7958904 G>C, rs12826786 C>T, and rs874945 C>T, for genotype frequency analysis and assessed the frequency of HOTAIR gene polymorphisms in 442 CAD patients and 418 randomly selected control subjects. To analyze the differences between these two populations, we performed a Student’s t-test, adjusted odds ratio (AOR), 95% confidence intervals (CIs), and ANOVA analysis. According to our baseline characteristic analysis, control subjects and CAD patients were significantly different in hypertension and diabetes mellitus. We also found that the rs4759314 A>G, rs1899663 G>T, and rs12826786 C>T genotypes were strongly associated with CAD susceptibility (AA vs. AG+GG: AOR = 0.608, 95% CI = 0.393−0.940, p = 0.025; GG vs. TT: AOR = 2.276, 95% CI = 1.125−4.607, p = 0.022; CC vs. CT+TT: AOR = 1.366, 95% CI = 1.027−1.818, p = 0.032, respectively). Our data also demonstrated that the genotype of HOTAIR polymorphisms, genotype combination, and haplotype analysis affect disease occurrence. Moreover, these polymorphisms are linked to clinical factors that contribute to disease susceptibility. In conclusion, results from our study suggest that HOTAIR polymorphisms may be useful novel biomarkers for diagnosing CAD. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)
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14 pages, 712 KiB  
Article
High versus Low-Moderate Intensity Exercise Training Program as an Adjunct to Antihypertensive Medication: A Pilot Clinical Study
by Vicente Ávila-Gandía, Maravillas Sánchez-Macarro, Antonio Luque-Rubia, Esther García-Sánchez, Fernando Cánovas, Asensio López-Santiago and Francisco Javier López-Román
J. Pers. Med. 2021, 11(4), 291; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11040291 - 10 Apr 2021
Cited by 2 | Viewed by 2128
Abstract
Objective: In this pilot clinical study we investigated the effect on blood pressure (BP) of two community-based exercise training programs of high (HIT) vs. low-moderate intensity (LMIT) in hypertensive individuals receiving at least one antihypertensive drug. Methods: The study included two phases of [...] Read more.
Objective: In this pilot clinical study we investigated the effect on blood pressure (BP) of two community-based exercise training programs of high (HIT) vs. low-moderate intensity (LMIT) in hypertensive individuals receiving at least one antihypertensive drug. Methods: The study included two phases of physical exercises based on 1-h session, 3 days/week for 12 and 16 weeks, respectively, separately by a 7-week resting period. Each phase was preceded by a four-week conditioning training period. According to the average maximal heart rate at baseline, participants were randomized to HIT (80–90%), LMIT (50–70%) or no-exercise (control). Heart rate was monitored during workout and BP profiles were registered by ambulatory BP monitoring at the beginning and end of each phase. Results: Of 60 individuals randomized, 44 completed the study (HIT, n = 10; LMIT, n = 16; controls, n = 18). BP levels were significantly reduced after the second phase for both LMIT (SBP −3.1 mmHg, DBP −2.4 mmHg) and HIT (SBP −10.8 mmHg, DBP −8.3 mmHg). Similar levels of improvement were also found in daytime and night-time BP. Mean attendance of the prescribed training sessions was 87.4 ± 6.2% for HIT and 87.4 ± 5.3% for LMIT during the first phase and 84.1 ± 5.0% and 85.2 ± 5.9% during the second phase, respectively (p = 0.047). Conclusion: Both HIT and LMIT exercise training programs reduced BP but the HIT modality showed a lower rate of compliance with proposed training schedule. Intensity of training should be individually prescribed to improve tolerance to more high intensity exercises. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)
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11 pages, 1087 KiB  
Article
Personalized Consideration of Admission-Glucose Gap between Estimated Average and Initial Glucose Levels on Short-Term Stroke Outcome
by Yerim Kim, Sang-Hwa Lee, Chulho Kim, Min Kyoung Kang, Byung-Woo Yoon, Tae Jung Kim, Jong Seok Bae and Ju-Hun Lee
J. Pers. Med. 2021, 11(2), 139; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11020139 - 18 Feb 2021
Cited by 4 | Viewed by 1524
Abstract
Background: Poststroke hyperglycemia is associated with poor outcomes. Most prior studies used initial glucose as an indicator of poststroke hyperglycemia without considering glycemic control status at the time of stroke occurrence. We aimed to investigate the effect of an admission-glucose gap on short-term [...] Read more.
Background: Poststroke hyperglycemia is associated with poor outcomes. Most prior studies used initial glucose as an indicator of poststroke hyperglycemia without considering glycemic control status at the time of stroke occurrence. We aimed to investigate the effect of an admission-glucose gap on short-term functional outcomes in acute ischemic stroke (AIS). Methods: We enrolled patients with AIS or transient ischemic attack who had been admitted within 7 days of symptom onset to three stroke centers from May 2016 to December 2019. The admission-glucose gap between estimated average glucose levels (eAG) and initial glucose level (eAG–initial glucose) was categorized into four groups. The short-term functional outcome was evaluated using the modified Rankin Scale (mRS) score at 3 months after stroke onset and was dichotomized. Results: Among 1332 included subjects, 548 (41.1%) had poor short-term functional outcomes. After adjusting for multiple variables, a severe negative glucose gap (eAG–initial glucose ≤ −50 mg/dL) was significantly associated with poor short-term functional outcome (OR, 1.573; 95% CI, 1.101–2.248). After dichotomizing glycemic control status, its significance was only maintained in the good glycemic control group (HbA1c < 6.5%) (OR, 1.914; 95% CI, 1.155–3.169). Conclusions: An elevated admission-glucose gap, in which the initial glucose level was much higher than the estimated glucose level was based on HbA1c, was associated with poor stroke prognosis. In addition to admission-glucose levels, glycemic control status at the time of stroke onset should be considered when predicting short-term stroke outcomes. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)
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14 pages, 244 KiB  
Article
Influence of SH2B3, MTHFD1L, GGCX, and ITGB3 Gene Polymorphisms on theVariability on Warfarin Dosage Requirements and Susceptibility to CVD in the Jordanian Population
by Laith N. AL-Eitan, Ayah Y. Almasri, Rame H. Khasawneh and Mansour A. Alghamdi
J. Pers. Med. 2020, 10(3), 117; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm10030117 - 09 Sep 2020
Cited by 3 | Viewed by 2965
Abstract
The purpose of this study was to investigate the effects of the SH2B3, MTHFD1L, GGCX, and ITGB3 gene variants on the efficacy of warfarin treatment and its effects on the risk of cardiovascular disorders in Jordanian patients. The selected genes [...] Read more.
The purpose of this study was to investigate the effects of the SH2B3, MTHFD1L, GGCX, and ITGB3 gene variants on the efficacy of warfarin treatment and its effects on the risk of cardiovascular disorders in Jordanian patients. The selected genes and their polymorphisms are involved in many Genome-Wide Association Study (GWAS) associated with cardiovascular disease and the variability of warfarin therapy. The current study conducted a genetic association and pharmacogenetics study in (212) Jordanian cardiovascular patients treated with warfarin and (213) healthy controls. DNA extraction and the Mass ARRAY™ system were used to genotype ten selected polymorphisms within four genes (SH2B3, MTHFD1L, GGCX, and ITGB3). This study confirmed a genetic association of MTHFD1L rs6922269 Single Nucleotide Polymorphism (SNP) with warfarin sensitivity during the initial and stabilization phases of treatment. Moreover, this SNP showed significant differences in the initial and maintenance doses of warfarin. This study also found an association between the genetic haplotypes (AGC and GAT) within the SH2B3 gene and responsiveness to warfarin. However, possession of an MTHFD1L rs491552 variant allele was found to affect the outcome measure of the international normalized ratio (INR) during the stabilization phase of warfarin treatment. In contrast, there was no association between all selected SNPs and susceptibility to cardiovascular disorders. This study extends the current understanding of the high variability of the warfarin response, including variability in dose requirements and susceptibility to cardiovascular disease in the Jordanian-Arab population. Other studies on a larger sample and in different ethnic groups could help to better understand the pharmacogenetics of warfarin and its application in personalized medicine. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)

Review

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11 pages, 909 KiB  
Review
Cardiovascular Risk Prediction Models and Scores in the Era of Personalized Medicine
by Areti Sofogianni, Nikolaos Stalikas, Christina Antza and Konstantinos Tziomalos
J. Pers. Med. 2022, 12(7), 1180; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12071180 - 20 Jul 2022
Cited by 18 | Viewed by 2719
Abstract
Cardiovascular disease (CVD) is the leading cause of death worldwide. Management of cardiovascular risk factors, particularly hypertension and dyslipidemia, has been shown to reduce cardiovascular morbidity and mortality. However, current guidelines recommend adjusting the intensity of blood pressure- and lipid-lowering treatment according to [...] Read more.
Cardiovascular disease (CVD) is the leading cause of death worldwide. Management of cardiovascular risk factors, particularly hypertension and dyslipidemia, has been shown to reduce cardiovascular morbidity and mortality. However, current guidelines recommend adjusting the intensity of blood pressure- and lipid-lowering treatment according to the cardiovascular risk of the patient. Therefore, cardiovascular risk prediction is a sine qua non for optimizing cardiovascular prevention strategies, particularly in patients without established CVD or type 2 diabetes mellitus (T2DM). As a result, several cardiovascular risk prediction equations have been developed. Nevertheless, it is still unclear which is the optimal prediction risk equation. In the present review, we summarize the current knowledge regarding the accuracy of the most widely used cardiovascular risk prediction equations. Notably, most of these risk scores have not been validated in external cohorts or were shown to over- or underestimate risk in populations other than those in which they derive. Accordingly, country-specific risk scores, where available, should be preferred for cardiovascular risk stratification. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)
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29 pages, 1200 KiB  
Review
MiRNAs and circRNAs for the Diagnosis of Anthracycline-Induced Cardiotoxicity in Breast Cancer Patients: A Narrative Review
by Roberto Rosenfeld, Silvia Riondino, Vincenzo Formica, Francesco Torino, Eugenio Martuscelli and Mario Roselli
J. Pers. Med. 2022, 12(7), 1059; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12071059 - 28 Jun 2022
Cited by 2 | Viewed by 2115
Abstract
Breast cancer (BC) is the most frequent type of female cancer with increasing incidence in recent years. Doxorubicin (DOX) is an important backbone chemotherapy in BC, responsible for cardiotoxicity (CTX) in about 9% of treated women within the first year. Biomarkers of early [...] Read more.
Breast cancer (BC) is the most frequent type of female cancer with increasing incidence in recent years. Doxorubicin (DOX) is an important backbone chemotherapy in BC, responsible for cardiotoxicity (CTX) in about 9% of treated women within the first year. Biomarkers of early CTX diagnosis are essential to avoid complicated DOX-related cardiac diseases. Traditional serum biomarkers are either poorly sensitive with transient elevation, and even absent if investigated outside their diagnostic window, or arise only in late-stage CTX. Emerging biomarkers such as non-coding RNA (ncRNA) have been recently investigated in DOX-related CTX. In our review, we revised the role of microRNAs, the most studied type of ncRNA, both in animal and human models, highlighting the interesting but often contrasting results. Moreover, we reviewed a novel class of ncRNA, circular RNA (circRNA), focusing on their modulatory mechanisms also involving microRNAs. MicroRNA and circRNA are players in a wide homeostatic balance with their perturbation representing a possible compensation for DOX damage. Further studies are required to assess the modalities of early detection of their variation in BC patients suffering from heart disease induced by DOX treatment. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)
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12 pages, 413 KiB  
Review
The Benefits of Telemedicine in Personalized Prevention of Cardiovascular Diseases (CVD): A Systematic Review
by Gopi Battineni, Getu Gamo Sagaro, Nalini Chintalapudi and Francesco Amenta
J. Pers. Med. 2021, 11(7), 658; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11070658 - 14 Jul 2021
Cited by 25 | Viewed by 6215
Abstract
Introduction: Adverse effects on personalized care and outcomes of cardiovascular diseases (CVD) could occur if health systems do not work in an efficient manner. The pandemic caused by COVID-19 has opened new perspectives for the execution and advancement of cardiovascular tests through telemedicine [...] Read more.
Introduction: Adverse effects on personalized care and outcomes of cardiovascular diseases (CVD) could occur if health systems do not work in an efficient manner. The pandemic caused by COVID-19 has opened new perspectives for the execution and advancement of cardiovascular tests through telemedicine platforms. Objective: This study aimed to analyze the usefulness of telemedical systems for providing personal care in the prevention of CVD. Methods: A systematic review analysis was conducted on the literature available from libraries such as PubMed (Medline), Scopus (Embase), and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Data available in the last 10 years (2011–2020) were also examined by PRISMA guidelines. The selected studies were divided into two categories: (1) benefits of telemedicine in CVD prevention, and (2) recent progress in telemedical services for personalized care of CVD. Results: The literature search produced 587 documents, and 19 articles were considered in this review. Results highlighted that the timely delivery of preventive care for CVD which can be implemented virtually can benefit and modify morbidity and mortality. This could also reduce the pressure on hospitals by decreasing acute CVD occurrence among the general population. The use of these technologies can also help to reduce access to hospitals and other medical devices when not necessary. Conclusions: Telemedicine platforms can be used for regular checkups for CVD and contribute to preventing the occurrence of acute events and more in general the progression of CVD. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)
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22 pages, 884 KiB  
Review
Personalized Genetic Diagnosis of Congenital Heart Defects in Newborns
by Olga María Diz, Rocio Toro, Sergi Cesar, Olga Gomez, Georgia Sarquella-Brugada and Oscar Campuzano
J. Pers. Med. 2021, 11(6), 562; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11060562 - 16 Jun 2021
Cited by 7 | Viewed by 6048
Abstract
Congenital heart disease is a group of pathologies characterized by structural malformations of the heart or great vessels. These alterations occur during the embryonic period and are the most frequently observed severe congenital malformations, the main cause of neonatal mortality due to malformation, [...] Read more.
Congenital heart disease is a group of pathologies characterized by structural malformations of the heart or great vessels. These alterations occur during the embryonic period and are the most frequently observed severe congenital malformations, the main cause of neonatal mortality due to malformation, and the second most frequent congenital malformations overall after malformations of the central nervous system. The severity of different types of congenital heart disease varies depending on the combination of associated anatomical defects. The causes of these malformations are usually considered multifactorial, but genetic variants play a key role. Currently, use of high-throughput genetic technologies allows identification of pathogenic aneuploidies, deletions/duplications of large segments, as well as rare single nucleotide variants. The high incidence of congenital heart disease as well as the associated complications makes it necessary to establish a diagnosis as early as possible to adopt the most appropriate measures in a personalized approach. In this review, we provide an exhaustive update of the genetic bases of the most frequent congenital heart diseases as well as other syndromes associated with congenital heart defects, and how genetic data can be translated to clinical practice in a personalized approach. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)
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