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PubMed2000

A cardiovascular EST repertoire: progress and promise for understanding cardiovascular disease.

The application of expressed sequence tag (EST) technology has proven to be an effective tool for gene discovery and the generation of gene expression profiles. The generation of an EST resource for the cardiovascular system has revealed significant insights into the changes in gene expression that guide heart development and disease. Furthermore, an important genetic resource has been developed for cardiovascular biology that is valuable for data mining and disease gene discovery.

Animals↗

PubMed1996

Effect of a physiological insulin infusion on the cardiovascular responses to a high fat meal: evidence supporting a role for insulin in modulating postprandial cardiovascular homoeostasis in man.

1. While the haemodynamic adjustments occurring after meal ingestion and the different effects of meals of different composition on these changes are well established, the mechanisms underlying these changes are less clear. Insulin, which has been shown to be both a positive inotrope and to stimulate vasodilatation in the skeletal muscle vascular bed, may account for the different cardiac and regional haemodynamic responses to high fat and high carbohydrate meals. 2. This study assessed the effect of an insulin infusion reproducing the plasma insulin profile seen after a high carbohydrate meal on the cardiovascular and regional haemodynamic response to a high fat meal. All measurements were carried out non-invasively in nine healthy lean subjects (mean age 24.5 +/- 1.3 years). 3. The high fat meal resulted in increases in cardiac output (0.7 +/- 0.32 l/min, P < 0.001), heart rate (7.8 +/- 2.1 beats/min, P < 0.001) and insulin (25.1 +/- 4.2 m-units/l, P < 0.001), and a decline in systemic vascular resistance (-1.9 +/- 0.9 units, P < 0.05) and superior mesenteric artery vascular resistance (-45 +/- 9 units, P < 0.01). After the high fat meal alone, calf vascular resistance and blood pressure did not change. After the high fat meal accompanied by insulin (peak insulin 86.1 +/- 10.1 m-units/l) there were greater cardiac responses [(P < 0.001); cardiac output, 1.17 +/- 0.36 l/min, and heart rate, 13.4 +/- 2.1 beats/min], and a larger fall in systemic vascular resistance and superior mesenteric artery vascular resistance. Unlike the high fat meal alone, the high fat meal with insulin was accompanied by a fall in calf vascular resistance (8.3 +/- 3.3 units) and blood pressure (3.8 +/- 1.6 mmHg). 4. The results of this study support a role for insulin in modulating postprandial cardiovascular homoeostasis; in particular, by its depressor action on skeletal muscle vasculature, insulin may in part contribute to the fall in blood pressure seen in the elderly, who have an inadequate cardiac response to the fall in systemic vascular resistance occurring after meal ingestion.

Adult↗

PubMed2026

Proteomic Profiling Captures Residual Cardiovascular Risk Beyond the PREVENT Model in Individuals With Cardiovascular-Kidney-Metabolic Syndrome Stages 2-3.

BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome reflects complex pathobiological interactions among metabolic disorders, kidney injury, and cardiovascular disease (CVD). Stages 2 and 3 represent critical phases of disease progression characterised by high pathological heterogeneity. This study aimed to develop a CVD protein risk score (PRS) for this population and evaluate its incremental predictive value over the PREVENT model. METHODS: This study included 24 017 participants with CKM Stages 2-3 from the UK Biobank. Using 2923 plasma proteins measured via the Olink platform, a PRS was developed in a training set (n = 19 218) using the LASSO method. In the validation set (n = 4799), the incremental predictive performance of this score over the PREVENT model was assessed using Harrell's C-statistic, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: A risk score comprising 63 proteins was constructed, primarily reflecting inflammation, kidney injury and matrix remodelling. Key proteins included growth differentiation factor 15 (GDF15), hepatitis A virus cellular receptor 1 (HAVCR1), matrix metallopeptidase 12 (MMP12) and NT-proBNP. In the validation set, after adjusting for PREVENT risk factors, individuals in the high PRS group had a 2.56-fold higher risk of CVD compared to those in the low score group (HR: 2.56, 95% CI: 1.96-3.37). Integrating the score into the PREVENT model improved the C-statistic by 0.034 (0.672-0.706) and achieved a 10-year NRI of 15.8% (95% CI: 9.5%-20.9%) and an IDI of 2.2% (95% CI: 1.3%-3.3%). CONCLUSION: Combining the PREVENT model with the PRS developed in this study enhances the prediction of future CVD events in the CKM Stages 2-3 population. This approach facilitates the capture of residual risk and supports precision risk stratification and management for this high-risk group.

Humans↗

PubMedDate not supplied

The first hypertension trial comparing the effects of two fixed-dose combination therapy regimens on cardiovascular events: Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypertension (ACCOMPLISH).

Current recommendations for the treatment of hypertension clarify the need to achieve lower blood pressure levels in the general population (<140/90 mm Hg) and in specific high-risk patient groups such as patients with diabetes or chronic renal disease (<130/80 mm Hg). Further, it is evident that to reach appropriate blood pressure control, most patients with high blood pressure will require two or more antihypertensive agents. There is scarce clinical trial outcome evidence to guide clinicians in the selection of optimal combinations of antihypertensive classes for high-risk hypertensive patients. A new clinical trial, Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH), is the first large clinical trial to directly compare cardiovascular mortality and morbidity rates for two fixed-dose combination therapies. Results from ACCOMPLISH should provide much-needed guidance for selecting optimal combination therapy for high-risk hypertensive patients.

Amlodipine↗

PubMed2001

Decoy oligodeoxynucleotides as novel cardiovascular drugs for cardiovascular disease.

Gene therapy is emerging as a potential strategy in the treatment of cardiovascular disease such as restenosis after angioplasty, vascular bypass graft occlusion, and transplant coronary vasculopathy, for which no known effective therapy exists. One strategy for combatting disease processes is to target the transcriptional process. Application of DNA technology such as antisense strategy to regulate the transcription of disease-related genes in vivo has important therapeutic potential. Recently, transfection of cis-element double-stranded oligodeoxynucleotides (= decoy) as a powerful tool in a new class of antigene strategies for gene therapy was reported. Transfection of double-stranded oligodeoxynucleotides corresponding to cis sequence will result in the attenuation of authentic cis-trans interaction, leading to the removal of transfactors from the endogenous cis-elements with subsequent modulation of gene expression. This "decoy" strategy is not only a novel strategy for gene therapy as an antigene strategy, but also a powerful tool for the study of endogenous gene regulation in vivo as well as in vitro. In this review, we focus on the future potential of decoy oligodeoxynucleotide-based gene therapy in the treatment of cardiovascular disease.

Cardiovascular Agents↗

PubMedDate not supplied

Subband modeling of the human cardiovascular system: new insights into cardiovascular regulation.

We present a new approach to cardiovascular analysis based on a well-known signal processing technique, namely, the frequency subband decomposition. The subbands are chosen in accordance with physiological standards: (1) 0-0.04 Hz, (2) 0.04-0.15 Hz, (3) 0.15-0.4 Hz. It is shown that such a pre-processing drastically improves the accuracy of the analysis and introduces a new direction in the understanding of the relationships between cardiovascular signals.

Adult↗

PubMed2006

Systems biology approaches to metabolic and cardiovascular disorders: network perspectives of cardiovascular metabolism.

In this review, we examine cardiovascular metabolism from three different, but highly complementary, perspectives. First, from the abstract perspective of a metabolite network, composed of nodes and links. We present fundamental concepts in network theory, including emergence, to illustrate how nature has designed metabolism with a hierarchal modular scale-free topology to provide a robust system of energy delivery. Second, from the physical perspective of a modular spatially compartmentalized network. We review evidence that cardiovascular metabolism is functionally compartmentalized, such that oxidative phosphorylation, glycolysis, and glycogenolysis preferentially channel ATP to ATPases in different cellular compartments, using creatine kinase and adenylate kinase to maximize efficient energy delivery. Third, from the dynamics perspective, as a network of dynamically interactive metabolic modules capable of self-oscillation. Whereas normally, cardiac metabolism exists in a regime in which excitation-metabolism coupling closely matches energy supply and demand, we describe how under stressful conditions, the network can be pushed into a qualitatively new dynamic regime, manifested as cell-wide oscillations in ATP levels, in which the coordination between energy supply and demand is lost. We speculate how this state of "metabolic fibrillation" leads to cell death if not corrected and discuss the implications for cardioprotection.

Animals↗

PubMed2002

Hepatocyte growth factor as cardiovascular hormone: role of HGF in the pathogenesis of cardiovascular disease.

Hepatocyte growth factor (HGF) is a mesenchyme-derived pleiotropic factor which regulates cell growth, cell motility, and morphogenesis of various types of cells, and is thus considered a humoral mediator of epithelial-mesenchymal interactions responsible for morphogenic tissue interactions during embryonic development and organogenesis. Although HGF was originally identified as a potent mitogen for hepatocytes, HGF has also been identified as a member of angiogenic growth factors. Interestingly, the presence of its specific receptor, c-met, is observed in vascular cells, endothelial cells and cardiac myocytes. In addition, the mitogenic action of HGF on human endothelial cells was most potent among growth factors. Recent studies have demonstrated the potential application of HGF to treat cardiovascular disease such as peripheral vascular disease, myocardial infarction and restenosis after angioplasty. On the other hand, serum HGF concentration was significantly correlated with blood pressure. These results suggest that HGF secretion might be elevated in response to high blood pressure as a counter-system against endothelial dysfunction, and may be considered as an index of severity of hypertension. In this review, we discussed the potential role of HGF in cardiovascular disease.

Angioplasty↗

PubMed2004

Advanced glycation endproduct crosslinking in the cardiovascular system: potential therapeutic target for cardiovascular disease.

Advanced glycation endproducts (AGEs) are formed by a reaction between reducing sugars and biological amines. Because of their marked stability, glycated proteins accumulate slowly over a person's lifespan, and can contribute to age-associated structural and physiological changes in the cardiovascular system such as increased vascular and myocardial stiffness, endothelial dysfunction, altered vascular injury responses and atherosclerotic plaque formation. The mechanisms by which AGEs affect the cardiovascular system include collagen crosslinking, alteration of low-density lipoprotein molecules and impairment of cellular nitric oxide signalling through their interaction with AGE receptors (RAGEs). Thus, the accumulation of AGEs may help to explain the increased cardiac risk associated with aging as well as diabetes mellitus and hypertension, two conditions that accelerate and enhance AGE formation. A variety of new pharmacological approaches are being developed to reduce the pathophysiological impact of AGEs. These agents can prevent AGE and AGE crosslink formation, break pre-existing AGE crosslinks, and block the interaction between AGEs and RAGEs. Such agents have been shown to reduce vascular and myocardial stiffness, inhibit atherosclerotic plaque formation and improve endothelial function in animal models. Improvement in vascular compliance has also been demonstrated with AGE crosslink breakers in clinical trials. These studies offer promise to reduce the cardiac risk associated with isolated systolic hypertension, diastolic dysfunction and diabetes.

Cardiovascular Diseases↗

PubMed2001

Prevalence of clinical and isolated subclinical cardiovascular disease in older adults with glucose disorders: the Cardiovascular Health Study.

OBJECTIVE: Clinical cardiovascular disease (CVD) is highly prevalent among people with diabetes. However, there is little information regarding the prevalence of subclinical CVD and its relation to clinical CVD in diabetes and in the glucose disorders that precede diabetes. RESEARCH DESIGN AND METHODS: Participants in the Cardiovascular Health Study, aged > or = 65 years (n = 5,888), underwent vascular and metabolic testing. Individuals with known disease in the coronary, cerebral, or peripheral circulations were considered to have clinical disease. Those without any clinical disease in whom CVD was detected by ultrasonography, electrocardiography, or ankle arm index in any of the three vascular beds were considered to have isolated subclinical disease. RESULTS: Approximately 30% of the cohort had clinical disease, and approximately 60% of the remainder had isolated subclinical disease. In those with normal glucose status, isolated subclinical disease made up most of the total CVD. With increasing glucose severity, the proportion of total CVD that was clinical disease increased; 75% of men and 66% of women with normal fasting glucose status had either clinical or subclinical CVD. Among those with known diabetes, the prevalence was approximately 88% (odds ratio [OR] 2.46 for men and 4.22 for women, P < 0.0001). There were intermediate prevalences and ORs for those with impaired fasting glucose status and newly diagnosed diabetes. CONCLUSIONS: Isolated subclinical CVD is common among older adults. Glucose disorders are associated with an increased prevalence of total CVD and an increased proportion of clinical disease relative to subclinical disease.

Aged↗

PubMed2001

Searching for preventive measures of cardiovascular events in aged Japanese taxi drivers--the daily rhythm of cardiovascular risk factors during a night duty day.

Previous studies have shown that Japanese taxi drivers are exposed to more risk factors and have a higher mortality rate due to cardiovascular disease than other occupational groups. We investigated the effect of night taxi driving with a view to preventing acute events of cardiovascular disease among aged taxi drivers. Twenty-nine taxi drivers (41-67 years old) were examined for urine normetanephrine/creatinine, von Willebrand factor, anti-thrombin III, t-plasminogen activator-plasminogen activator inhibitor 1-complex, hematocrit, blood glucose and blood pressure in the morning and at midnight during a duty day and in the following morning. At the same time, the blood pressure and blood glucose of 46 taxi drivers (43-67 years old) in the morning after a night duty with little sleep and in the morning after daytime work and subsequent night sleep were compared. The results obtained indicate that the aggravation of sympathetic nervous system functions with disturbed circadian rhythms, increased blood coagulation and blood concentration, endothelial injury and the elevation of blood glucose at midnight or the next morning were induced by their night work. These conditions are supposed to favour acute vascular events in aged taxi drivers. Preventive measures considered include social support for anticoagulant food and water intake, short exercise and walking as well as taking a rest and a nap during night work.

Adult↗

PubMed2006

[Influence of the arterio-venous fistula on cardiovascular system in patients with particular cardiovascular risk].

In the population of hemodialysis patients the risk of ischemic heart disease and morbidity related to it, is considerably higher than in general population. In the group of elderly hemodialysed patients and in patients with diabetes this risk is even higher Additional risk factors of cardiovascular disease are those specific for renal insufficiency, including the presence of arterio-venous fistula, which is believed to be an independent risk factor for cardiovascular disease through the promotion of hyperkinetic circulation. In the study the impact of the arterio-venous fistula on heart function in Doppler USG in the group of 16 elderly hemodialysis patients (aged 79, 4 +/- 5,4), 10 diabetics with type 2 diabetes (aged 63,2 +/- 10,4) and 7 hemodialysis patients younger and without diabetes was examined. In all patients arterio-venous fistula was created on the forearm from native vessels. The following hemodynamic USG parameters of heart function were assessed: ejection fraction (EF), shortening fraction (FS), stroke volume (SV) and cardiac output (CO). We conclude that impact of native arterio-venous fistula created on forearm on circulation in the group of elderly and diabetic patients is of the same magnitude as in the group of younger, non diabetic patients.

Aged↗

PubMed1985

Continuous subcutaneous insulin infusion therapy (CSII) influences cardiovascular responses to graded exercise in patients with autonomic diabetic neuropathy of the cardiovascular system (ADNCS).

We have demonstrated previously the effect of CSII on diabetics with ADNCS. In this study 16 Type-1-diabetics with ADNCS, 20 diabetics without ADNCS and 20 non diabetic controls were examined. Mean age and mean diabetes duration were similar in all groups. Graded exercise was performed in all patients using an ergometer cycle. In patients with ADNCS resting heart rate was significantly higher. The increase in heart rate during exercise was significantly lower, maximal tolerated work load was significantly reduced, and blood pressure-heart-rate multiplication as indirect measurement of oxygen uptake was significantly reduced too. The 16 diabetics with ADNCS were divided into 2 groups: 6 patients got CSII (12 months), 10 patients continued conventional s.c. therapy. After 6 and after 12 months graded exercise was performed again. The patients on s.c. therapy showed no improvement. 3 of the 6 CSII treated patients showed a significant improvement of the above mentioned parameters. Thus, in diabetics with ADNCS, CSII might not only influence the cardiovascular reflex tests, but might also have an effect on cardiovascular responses to graded exercise.

Autonomic Nervous System Diseases↗

PubMed2006

Quantitative retinal venular caliber and risk of cardiovascular disease in older persons: the cardiovascular health study.

BACKGROUND: Small vessel disease may contribute to the risk of cardiovascular disease in older persons. We describe the relation of retinal vascular caliber to incident coronary heart disease (CHD) and stroke in elderly persons. METHODS: Prospective population-based cohort study composed of 1992 men and women aged 69 to 97 years living in 4 US communities. Retinal arteriolar and venular calibers were measured from retinal photographs using a computer-assisted method. Incident CHD and stroke events were ascertained using standardized methods. RESULTS: After 5 years of follow-up, there were 115 incident CHD events and 113 incident stroke events. Participants with larger retinal venular caliber had a higher incidence of CHD (11.7%; 95% confidence interval [CI], 8.7%-15.8%, vs 8.1%; 95% CI, 5.7%-11.6%), comparing largest with smallest venular caliber quartiles, and stroke (8.4%; 95% CI, 6.0-11.7, vs 5.8%; 95% CI, 3.9-8.4). At multivariable analysis, controlling for age, sex, race, arteriolar caliber, systolic and diastolic blood pressure, diabetes, glucose concentration, cigarette smoking, pack-years of smoking, and high-density-lipoprotein and low-density lipoprotein cholesterol levels, larger retinal venular caliber was associated with incident CHD (rate ratio, 3.0; 95% CI, 1.6-5.7, comparing largest with smallest venular caliber quartiles; P(trend) = .001) and incident stroke (rate ratio, 2.2; 95% CI, 1.1-4.3; P(trend) = .02). Additional adjustment for C-reactive protein and common and internal carotid artery intimal-media thickness had minimal effect on these associations. At multivariable analysis, smaller retinal arteriolar caliber was associated with incident CHD (rate ratio, 2.0; 95% CI, 1.1-3.7, comparing largest with smallest arteriolar caliber quartiles; P = .03) but not stroke (rate ratio,1.1; 95% CI, 0.5-2.2; P = .73). CONCLUSION: Larger retinal venular caliber is independently associated with risk of cardiovascular disease in elderly persons.

Aged↗

PubMed2004

Favorable cardiovascular risk profile in young women and long-term risk of cardiovascular and all-cause mortality.

CONTEXT: For women, impact of cardiovascular risk factors measured in young adulthood, particularly favorable (low-risk) profile, on mortality has been difficult to assess due to low short-term death rates. OBJECTIVE: To assess the relationship of baseline coronary risk factor status to mortality from coronary heart disease (CHD), cardiovascular diseases (CVDs), and all causes in young women. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: A total of 7302 women aged 18 to 39 years without prior CHD or major electrocardiographic abnormalities screened between 1967 and 1973 for the Chicago Heart Association Detection Project in Industry. Risk groups were defined using national guidelines for values of systolic and diastolic blood pressure, serum cholesterol level, body mass index, presence of diabetes, and smoking status. Participants were divided into 4 groups: low risk, 0 risk factors high but 1 or more unfavorable, 1 only risk factor high, and 2 or more risk factors high. MAIN OUTCOME MEASURES: All-cause mortality, CHD mortality, and CVD mortality; hazard ratio of outcome measures comparing low-risk group with other groups. RESULTS: Only 20% met low-risk criteria; 59% had high levels of 1 or more risk factors. During an average follow-up of 31 years, there were 47 CHD deaths, 94 CVD deaths, and 469 deaths from all causes. The age-adjusted CVD death rate per 10,000 person-years was lowest for low-risk women and increased with the number of risk factors, ie, 1.5, 1.7, 5.0, and 9.1 for low-risk; 0, 1, and 2 or more risk factors high, respectively. Multivariate-adjusted CVD mortality hazard ratio for low-risk women was 0.19 (95% confidence interval, 0.08-0.45) compared with women with 2 or more risk factors high. Similar patterns were observed for CHD and all-cause mortality and for both blacks and whites. CONCLUSION: For women with favorable levels for all 5 major risk factors at younger ages, CHD and CVD are rare; long-term and all-cause mortality are much lower compared with others.

Adult↗

PubMed2001

Cardiovascular genomics: estimating the total number of genes expressed in the human cardiovascular system.

The number of genes encoded by the human genome has long sought to be determined. With the recent publications of the complete sequence of the human genome, the number of genes encoded by the human genome has now been estimated to be approximately 32,000-38,000. Now the next step will be to determine which of these genes are expressed in a given cell, tissue or organ. Using three unique approaches taking advantage of our current cardiovascular EST database and the complete nucleotide sequence of human chromosomes 21 and 22 as well as cDNA microarray hybridization, we estimate that between 20,930-27,160 genes are expressed in the cardiovascular system.

Cardiovascular System↗

PubMed1989

Cardiovascular mortality in the Federal Republic of Germany, 1970-79, and the evaluation of the German Cardiovascular Prevention Study: results from a geographic mortality study.

The primary endpoint of the German Cardiovascular Prevention Study (GCP), cardiovascular mortality, has to be based on the official mortality statistics. In the scope of a geographic mortality study trends and regional variations of ischemic heart disease (ICD-9, 410-414) and cerebrovascular disease (ICD-9, 430-438) mortality were investigated. During the study period from 1970 to 1979 a relevant decline of cerebrovascular diseases in men and women was observed, whereas ischemic heart disease mortality figures remained relatively stable. Over time the importance of ischemic heart disease mortality has increased. The geographic analysis points to relevant problems concerning the validity of mortality data due to the particularities of the German mortality statistics (separately signed in the 11 statistical offices of the 11 federal states). The mortality rates of the four intervention regions of the "Kooperative Prävention" (corresponding data of "Kommunale Prävention" not available) indicate that the intervention regions are at a considerably lower level than the FRG, the mortality patterns, however, paralleling those of the FRG. As far as mortality structures are concerned, ischemic heart diseases are more important in the intervention regions than in the FRG as a whole.

Adult↗

PubMed1995

Black-white differences in subclinical cardiovascular disease among older adults: the Cardiovascular Health Study. CHS Collaborative Research Group.

Cardiovascular and all-cause mortality are higher in black than white Americans, but racial differences in clinical and subclinical cardiovascular disease (CVD) have not been examined in older adults. Clinical and subclinical CVD and its risk factors were compared in 4926 white and 244 black men and women aged 65 years and older. Black participants had lower socioeconomic status and generally higher prevalences of CVD and its risk factors, except for adverse lipid profiles. Common carotid wall thickness was greater in black than white women, and ankle-arm blood pressure ratios were lower in black women and men (p < 0.01). After adjustment for CVD risk factors, common carotid walls were significantly thicker and ankle-arm ratios were lower in blacks than whites of both sexes, while internal carotid walls were significantly thinner in black women. Racial differences in clinical and subclinical CVD in older adults are similar to those reported in younger populations and do not appear to be explained by CVD risk factors.

Aged↗