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Life Sciences Jun 2024Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide, primarily affecting the heart and blood vessels, with atherosclerosis being a major... (Review)
Review
Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide, primarily affecting the heart and blood vessels, with atherosclerosis being a major contributing factor to their onset. Epidemiological and clinical studies have linked high levels of low-density lipoprotein (LDL) emanating from distorted cholesterol homeostasis as its major predisposing factor. Cholesterol homeostasis, which involves maintaining the balance in body cholesterol level, is mediated by several proteins or receptors, transcription factors, and even genes, regulating cholesterol influx (through dietary intake or de novo synthesis) and efflux (by their conversion to bile acids). Previous knowledge about CVDs management has evolved around modulating these receptors' activities through synthetic small molecules/antibodies, with limited interest in natural products. The central roles of the cholesteryl ester transfer protein (CETP), proprotein convertase subtilisin/kexin type 9 (PCSK9), and cytochrome P450 family 7 subfamily A member 1 (CYP7A1), among other proteins or receptors, have fostered growing scientific interests in understanding more on their regulatory activities and potential as drug targets. We present up-to-date knowledge on the contributions of CETP, PCSK9, and CYP7A1 toward CVDs, highlighting the clinical successes and failures of small molecules/antibodies to modulate their activities. In recommendation for a new direction to improve cardiovascular health, we have presented recent findings on natural products (including functional food, plant extracts, phytochemicals, bioactive peptides, and therapeutic carbohydrates) that also modulate the activities of CETP, PCSK-9, and CYP7A1, and emphasized the need for more research efforts redirected toward unraveling more on natural products potentials even at clinical trial level for CVD management.
PubMed: 38866219
DOI: 10.1016/j.lfs.2024.122823 -
Clinics in Shoulder and Elbow Jun 2024Little is known about alterations of the rotator cuff (RC) macroscopic vasculature associated with medical conditions and/or habits that predispose a person to diseases...
BACKGROUND
Little is known about alterations of the rotator cuff (RC) macroscopic vasculature associated with medical conditions and/or habits that predispose a person to diseases of the peripheral microcirculation. The high frequency of cuff tear and re-tear in patients with diabetes, hypercholesterolemia, uncontrolled arterial hypertension, or metabolic syndrome may be due to tissue hypovascularity.
METHODS
The macroscopic vasculature of both the articular and bursal sides of the posterosuperior RC was evaluated arthroscopically in 107 patients (mean age, 58.2 years) with no RC tear. Patients were divided into three groups according to medical comorbidities and lifestyle factors (group I, none; group II, smokers and/or drinkers and one comorbidity; and group III, two or more comorbidities). Pulsating vessels originating from both the myotendinous and osteotendinous junctions were assessed as "clearly evident," "poorly evident," or "not evident."
RESULTS
Groups I, II, and III comprised 36, 45, and 26 patients, respectively. Within the myotendinous junction, vessels were visualized in 22 group I patients (61%), 25 group II patients (55%), and 6 group III patients (23%) (P=0.007). Pulsating arterial vessels originating from the osteotendinous junction were seen in 42%, 36%, and 0% of patients, respectively (P<0.001). Within the bursal side of the RC, a dense anastomotic network was visualized (either clearly or poorly) in 94% (34), 80% (36), and 35% (9) of patients, respectively (P<0.001).
CONCLUSIONS
The macroscopic vasculature of the RC is influenced by pre-existing diseases and lifestyle factors, which may impair peripheral microcirculation. Level of evidence: III.
PubMed: 38863404
DOI: 10.5397/cise.2024.00066 -
BMC Geriatrics Jun 2024The global population is ageing rapidly and it is important to promote healthy ageing. The Healthy Ageing Index (HAI) is a comprehensive measure of health, but there is...
BACKGROUND
The global population is ageing rapidly and it is important to promote healthy ageing. The Healthy Ageing Index (HAI) is a comprehensive measure of health, but there is limited research on its association with other age-related outcomes. The management of an aging population necessitates considerations even among generally healthy adults, as age-related diseases often remain unaccounted for until later stages of life. This study explores the association of risk factors with HAI and its association with peripheral artery disease (PAD), muscle strength, health-related quality of life (HRQoL), and psychological distress in the Singapore Multi-Ethnic Cohort study.
METHODS
This cross-sectional study involved 1909 participants (median (Q1, Q3) age: 53 (48, 60) years and 59.3% females) from Singapore Multi-Ethnic Cohort study. The risk factors of HAI included age, gender, ethnicity, education level, smoking, alcohol consumption, employment, BMI and past medical histories. PAD was assessed using ankle-brachial index (ABI), handgrip strength (HGS), HRQoL with the EQ-5D-5 L questionnaire and psychological distress via the Kessler Psychological Distress Scale (K10). HAI components were assessed using relevant marker tests.
RESULTS
Older age, Malay and Indian ethnicities, unemployment, high BMI and histories of CHD, hypercholesterolaemia, tumours and TIA/stroke were associated with lower HAI scores indicative of poorer health. Higher HAI scores were associated with females and higher education levels. Lower HAI scores were significantly associated with low ABI, high K10 scores, mobility and anxiety/depression dimensions of EQ-5D-5 L.
CONCLUSION
The most important factors associated with HAI were age, sex, ethnicity, education, unemployment, BMI and a history of health conditions. Lower HAI scores were significantly associated with PAD, lower HRQoL and psychological distress. Thus, the HAI demonstrates promise as an evaluation method for assessing PAD, overall muscle strength and HRQoL in a population-based setting.
Topics: Humans; Female; Male; Singapore; Middle Aged; Cross-Sectional Studies; Quality of Life; Healthy Aging; Cohort Studies; Risk Factors; Peripheral Arterial Disease; Ethnicity; Aged; Hand Strength; Muscle Strength
PubMed: 38862903
DOI: 10.1186/s12877-024-05099-7 -
Stem Cell Research Aug 2024Familial hypercholesterolemia (FH) is a genetic disorder affecting the metabolism of lipoprotein, characterized by elevated levels of plasma concentrations of...
Familial hypercholesterolemia (FH) is a genetic disorder affecting the metabolism of lipoprotein, characterized by elevated levels of plasma concentrations of low-density lipoprotein cholesterol (LDLC). The most common FH cause is mutations within the gene that encodes for the LDL receptor (LDLR) protein. Two induced pluripotent stem cell (iPSC) lines were generated from patients with FH, each carrying a single heterozygous mutation in the LDLR gene, one is a missense mutation, c.631C > T, and the other is a splice-site mutation, c.313 + 1G > A. Both iPSC lines exhibited strong expression of pluripotency markers, demonstrated the ability to differentiate into derivatives of the three germ layers, and maintained normal karyotypes. These derived iPSC lines represent powerful tools for in vitro modeling FH and offer a promising platform for therapeutic development.
Topics: Induced Pluripotent Stem Cells; Receptors, LDL; Humans; Hyperlipoproteinemia Type II; Heterozygote; Mutation; Cell Line; Male; Female; Cell Differentiation
PubMed: 38852422
DOI: 10.1016/j.scr.2024.103463 -
Current Health Sciences Journal 2024The aim of this study was to examine two hypotheses: 1) Users of Day Care Center for Elderly (DCCE) would have frail health and multiple age-related care needs, and 2)...
AIM
The aim of this study was to examine two hypotheses: 1) Users of Day Care Center for Elderly (DCCE) would have frail health and multiple age-related care needs, and 2) caregivers would have to deal with some levels of anxiety due to the burden of care, and similar levels of quality of life to the users.
MATERIALS AND METHODS
The current cross-sectional study was carried out at a DCCE of the regional unit of Heraklion, Crete, Greece, between March-April 2022. The study sample comprised 29 DCCE social care services users and 51 caregivers. A short questionnaire sheet was created to record sociodemographic characteristics and general health-related issues. Additionally, the Anxiety Symptom Scale (Short Anxiety Screening Test (SAST)) and the Quality of Life (SF-12) were used to measure anxiety and quality of life of the participants. Comparison analysis was performed to detect differences between the two groups.
RESULTS
The most common morbidities for users of DCCE were hypertension (58.6%), hypercholesterolemia (55.2%), rheumatoid arthritis (24.1%), diabetes (24.1%) and heart disease (41.4%). Users of social care services have significantly higher vaccination rates (influenza: 100%, COVID-19: 100%, herpes zoster: 44.8%, and pneumococcus: 86.2%) than their caregivers. About 75% (yes: 24% and sometimes: 51.8%) of the users and 45% of their caregivers (yes: 7.8%, and sometimes: 37.3%) felt lonely at least sometimes. All participants were found to have low mean levels of the SAST score (18.4, SD:4.9) and 18.7% were on the verge of severe symptoms. Users of social care services were found to have low average levels of quality of life (SF-12), with significantly lower physical health (28.2, SD: 6.6) compared to the Mental health subscale (39.6, SD: 9.3) (p <0.001).
CONCLUSIONS
This study highlighted the main health-issues of DCCE users, and that they have low quality of life. Additionally, we found that caregivers faced a few health-issues, and had higher quality of life and lower SAST levels than the users. Therefore, social and health policy providers should consider our findings and assess the users' and caregivers' needs to provide holistic care, thus improving their quality of life.
PubMed: 38846480
DOI: 10.12865/CHSJ.50.01.15 -
Archives of Medical Sciences.... 2024Common therapies for cardiovascular diseases (CVDs) are associated with wide side effects. Thus, herbal medicines have been regarded due to fewer side effects,...
Common therapies for cardiovascular diseases (CVDs) are associated with wide side effects. Thus, herbal medicines have been regarded due to fewer side effects, availability, cultural beliefs, and being cheap. For thousand years, herbal medicine has been used for bacterial infections, colds, coughs, and CVDs. Cinnamon bark contains phenolic compounds such as cinnamaldehyde and cinnamic acid with protective properties which can reduce the risk of cardiovascular diseases, cardiac ischemia and hypertrophy, and myocardial infarction. Furthermore, cinnamon has antioxidant and anti-inflammatory properties and exhibits beneficial effects on the complications of diabetes, obesity, hypercholesterolemia, and hypertension which cause CVDs. Although the protective effects of cinnamon on the heart have been reported in many studies, it needs more clinical studies to prove the pharmaceutical and therapeutic efficacy of cinnamon on risk factors of CVDs.
PubMed: 38846056
DOI: 10.5114/amsad/184245 -
Clinical and Translational Science Jun 2024Homozygous familial hypercholesterolemia (HoFH) is a rare and serious genetic condition characterized by premature cardiovascular disease due to severely elevated... (Review)
Review
Homozygous familial hypercholesterolemia (HoFH) is a rare and serious genetic condition characterized by premature cardiovascular disease due to severely elevated low-density lipoprotein cholesterol (LDL-C). HoFH primarily results from loss-of-function (LOF) mutations in the LDL receptor (LDLR), reducing LDL-C clearance such that patients experience severe hypercholesterolemia, exacerbating the risk of developing cardiovascular events. Treatment options such as statins, lomitapide, ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, and apheresis help lower LDL-C; however, many patients with HoFH still fail to reach their target LDL-C levels and many of these lipid-lowering therapies are not indicated for pediatric use. Angiopoietin-like protein 3 (ANGPTL3) has been identified as a target to treat elevated LDL-C by acting as a natural inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL), enzymes involved in the hydrolysis of the triglyceride and phospholipid content of very low-density lipoproteins. Persons heterozygous for LOF mutations in ANGPTL3 were reported to have lower LDL-C than non-carriers and lower risk of coronary artery disease. Evinacumab is a first-in-class human monoclonal antibody that specifically binds to ANGPTL3 to prevent its inhibition of LPL and EL. In clinical trials, a 15 mg/kg intravenous dose every 4 weeks has shown a mean percent change from baseline in LDL-C of ~50% in adult, adolescent, and pediatric patients with HoFH. This mini review article describes the mechanism of action of evinacumab, evinacumab population PK and PD modeling, and clinical development history of evinacumab for the treatment of HoFH.
Topics: Humans; Translational Research, Biomedical; Hyperlipoproteinemia Type II; Angiopoietin-Like Protein 3; Cholesterol, LDL; Antibodies, Monoclonal; Broadly Neutralizing Antibodies; Animals; Anticholesteremic Agents; Receptors, LDL
PubMed: 38845393
DOI: 10.1111/cts.13836 -
Open Heart Jun 2024There is increasing awareness that patients without standard modifiable risk factors (SMuRFs; diabetes, hypercholesterolaemia, hypertension and smoking) may represent a...
BACKGROUND
There is increasing awareness that patients without standard modifiable risk factors (SMuRFs; diabetes, hypercholesterolaemia, hypertension and smoking) may represent a unique subset of patients with acute coronary syndrome (ACS). We aimed to investigate the prevalence and outcomes of patients with SMuRF-less ACS undergoing percutaneous coronary intervention (PCI) compared with those with SMuRFs.
METHODS
We analysed data from the Melbourne Interventional Group PCI Registry. Patients with coronary artery disease were excluded. The primary outcome was 30-day mortality. Secondary outcomes included in-hospital and 30-day events. Long-term mortality was investigated using Cox-proportional hazards regression.
RESULTS
From 1 January 2005 to 31 December 2020, 2727/18 988 (14.4%) patients were SMuRF less, with the proportion increasing over time. Mean age was similar for patients with and without SMuRFs (63 years), and fewer females were SMuRF-less (19.8% vs 25.4%, p<0.001). SMuRF-less patients were more likely to present with cardiac arrest (6.6% vs 3.9%, p<0.001) and ST-elevation myocardial infarction (59.1% vs 50.8%, p<0.001) and were more likely to experience postprocedural cardiogenic shock (4.5% vs 3.6%, p=0.019) and arrhythmia (11.2% vs 9.9%, p=0.029). At 30 days, mortality, myocardial infarction, revascularisation and major adverse cardiac and cerebrovascular events did not differ between the groups. During median follow-up of 7 years, SMuRF-less patients had an adjusted 13% decreased rate of mortality (HR 0.87 (95% CI 0.78 to 0.97)).
CONCLUSIONS
The proportion of SMuRF-less patients increased over time. Presentation was more often a devastating cardiac event compared with those with SMuRFs. No difference in 30-day outcomes was observed and SMuRF-less patients had lower hazard for long-term mortality.
Topics: Humans; Acute Coronary Syndrome; Female; Male; Percutaneous Coronary Intervention; Middle Aged; Prevalence; Registries; Aged; Risk Factors; Treatment Outcome; Time Factors; Risk Assessment; Retrospective Studies; Follow-Up Studies; Survival Rate; Hospital Mortality; Victoria
PubMed: 38843905
DOI: 10.1136/openhrt-2024-002733 -
Indian Journal of Dermatology,... May 2024
PubMed: 38841948
DOI: 10.25259/IJDVL_980_2023 -
Circulation Jun 2024Quantifying the economic burden of cardiovascular disease and stroke over the coming decades may inform policy, health system, and community-level interventions for... (Review)
Review
BACKGROUND
Quantifying the economic burden of cardiovascular disease and stroke over the coming decades may inform policy, health system, and community-level interventions for prevention and treatment.
METHODS
We used nationally representative health, economic, and demographic data to project health care costs attributable to key cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia) and conditions (coronary heart disease, stroke, heart failure, atrial fibrillation) through 2050. The human capital approach was used to estimate productivity losses from morbidity and premature mortality due to cardiovascular conditions.
RESULTS
One in 3 US adults received care for a cardiovascular risk factor or condition in 2020. Annual inflation-adjusted (2022 US dollars) health care costs of cardiovascular risk factors are projected to triple between 2020 and 2050, from $400 billion to $1344 billion. For cardiovascular conditions, annual health care costs are projected to almost quadruple, from $393 billion to $1490 billion, and productivity losses are projected to increase by 54%, from $234 billion to $361 billion. Stroke is projected to account for the largest absolute increase in costs. Large relative increases among the Asian American population (497%) and Hispanic American population (489%) reflect the projected increases in the size of these populations.
CONCLUSIONS
The economic burden of cardiovascular risk factors and overt cardiovascular disease in the United States is projected to increase substantially in the coming decades. Development and deployment of cost-effective programs and policies to promote cardiovascular health are urgently needed to rein in costs and to equitably enhance population health.
PubMed: 38832515
DOI: 10.1161/CIR.0000000000001258