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The role of arachidonic acid metabolites in cardiovascular homeostasis. Biochemical, histological and clinical cardiovascular effects of non-steroidal anti-inflammatory drugs and their interactions with cardiovascular drugs.

Derivatives of arachidonic acid may be involved in atherosclerosis and its clinical complications. There is much interest in pharmacologically manipulating the arachidonic acid cascade as a means of preventing cardiovascular disease. The development of atherosclerosis has been intensively studied and the consequences of cardiovascular or cerebrovascular vessel occlusion are too familiar. Many factors are probably involved, but the role of plasma lipoproteins and the interactions between various constituents of blood and blood vessel walls have received particular attention. The risk of cardiovascular disease associated with high plasma concentrations of the low density lipoproteins and the possible protective effects of high density lipoproteins have been well documented. Much is now known about lipoprotein biochemistry, and the importance of controlling the quantity and quality of dietary lipids has been demonstrated in epidemiological studies. In studies of patients with transient ischaemic attacks, aspirin reduced the risk of stroke and death in males, although these benefits were not as convincingly demonstrated in women. The majority of patients were given aspirin 1300 mg daily, but the optimum dosage was not properly evaluated. Administering aspirin in combination with another antiplatelet drug did not appear to offer any therapeutic advantage in these patients. Aspirin showed a positive, but non-significant trend towards reduced numbers of cardiac events, non-fatal infarcts and total mortality in patients who had experienced at least one myocardial infarction. In contrast, statistically significant beneficial effects were recorded when patients with unstable angina were administered aspirin. The risks of myocardial infarction or coronary death were reduced by 51% in 2 large studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis

Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without preexisting cardiovascular disease.

To determine the associations of total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol with mortality from coronary heart disease and cardiovascular disease, we studied 2541 white men who were 40 to 69 years old at base line and followed them for an average of 10.1 years. Seventeen percent had some manifestation of cardiovascular disease at base line, whereas the others did not. Among the men who had cardiovascular disease at base line, we found, after multivariate adjustment, that those with "high" blood cholesterol levels (above 6.19 mmol per liter) had a risk of death from cardiovascular disease, including coronary heart disease, that was 3.45 times higher (95 percent confidence interval, 1.63 to 7.33) than that for men with "desirable" blood cholesterol levels (below 5.16 mmol per liter). The corresponding hazard ratios were 5.92 (95 percent confidence interval, 2.59 to 13.51) for LDL cholesterol levels above 4.13 mmol per liter as compared with those below 3.35 mmol per liter, and 6.02 (95 percent confidence interval, 2.73 to 13.28) for HDL cholesterol levels below 0.90 mmol per liter as compared with those above 1.16 mmol per liter. All three lipid levels were also significant predictors of death from coronary heart disease alone (P less than 0.005). Total cholesterol and LDL cholesterol levels were also significant predictors of death from cardiovascular and coronary heart disease in men without preexisting cardiovascular disease, although at a lower level of absolute risk of death. Thus, the 10-year risk of death from cardiovascular disease for a man with preexisting cardiovascular disease increased from 3.8 percent to almost 19.6 percent with increasing levels of total cholesterol from "desirable" to "high," whereas the corresponding risk for a man who was free of cardiovascular disease at base line increased from 1.7 percent to 4.9 percent. Our findings suggest that total, LDL, and HDL cholesterol levels predict subsequent mortality in men 40 to 69 years of age, especially those with preexisting cardiovascular disease.

Adult

Cardioprotective glucose-lowering drugs, statins, and secondary major adverse cardiovascular events: a nationwide cohort study of individuals with type 2 diabetes and cardiovascular disease.

BACKGROUND: In type 2 diabetes, cardioprotective glucose-lowering drugs, including sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, and statins reduce the risk of secondary major adverse cardiovascular events. No trials examined the combination of these drugs as withholding statins in high-risk individuals would be unethical. We tested the hypothesis that cardioprotective glucose-lowering drug and statin combined is associated with lower risk of secondary major adverse cardiovascular events than either drug alone. METHODS: Individuals with type 2 diabetes and established cardiovascular disease from December 2012 through 2021 were identified via national Danish health registers. They were analyzed in an active comparator cohort including 15,404 individuals followed from treatment intensification with cardioprotective glucose-lowering drug or dipeptidyl peptidase-4 inhibitor and additionally in a time-varying cohort including 76,853 individuals with yearly updated treatment and covariate status. The treatment groups were: (i) no cardioprotective drug (no use of cardioprotective glucose-lowering drug or statin), (ii) cardioprotective glucose-lowering drug, (iii) statin, and (iv) cardioprotective glucose-lowering drug and statin. The primary outcome was a new major adverse cardiovascular event (myocardial infarction, stroke, or cardiovascular death). RESULTS: During mean 2.7 and 4.7 years of follow-up, 1,843 and 23,051 had major adverse cardiovascular events in the active comparator and time-varying cohorts. In the active comparator cohort, when compared to nonusers of cardioprotective glucose-lowering drug or statin, multivariable adjusted hazard ratios of major adverse cardiovascular events were 0.82 (95% confidence interval: 0.67 to 1.02) for cardioprotective glucose-lowering drug, 0.85 (0.74 to 0.97) for statin, and 0.71 (0.60 to 0.84) for cardioprotective glucose-lowering drug and statin combined. Corresponding hazard ratios in the time-varying cohort were 0.77 (0.69 to 0.86), 0.73 (0.70 to 0.75), and 0.57 (0.54 to 0.60), respectively. When restricting the active comparator cohort to individuals entering observation between 2019 and 2021 with reduced statistical power, the corresponding hazard ratios were 0.86 (0.57 to 1.31), 0.89 (0.60 to 1.30), and 0.79 (0.54 to 1.14), respectively. In both cohorts p for interaction between cardioprotective glucose-lowering drug and statin was > 0.05. CONCLUSIONS AND RELEVANCE: In individuals with type 2 diabetes and established cardiovascular disease, treatment with a cardioprotective glucose-lowering drug and statin in combination was associated with lower risk of secondary major adverse cardiovascular events than using either drug alone. This is important given the persistently suboptimal uptake of both drug classes in real-world practice. Some biases can never be completely excluded in real-world pharmacotherapy use studies such as this one, including confounding by indication, time-related or immortal time biases, and shifting standards of care, rendering causal interpretation unattainable; however, our results seemed consistent across numerous sensitivity analyses and designs.

Humans

Cardiovascular simulation using a multiple modeling method on a digital computer--simulation of interaction between the cardiovascular system and angiotensin II.

A cardiovascular system model that simulates interactive responses to drugs has been developed on a small digital computer. The overall model basically consists of three models. The first is a momentum transport model that represents relations between blood pressure and flow in the cardiovascular system. In this model, the cardiovascular system is divided into 14 components and modeled by using equivalent electrical circuits. The second is a mass transport model comprising 14 compartments corresponding to the respective components of the cardiovascular system. This model represents the distribution of the administered drug in the various cardiovascular components. The third is an interaction model that represents the relationships between the momentum and mass transport models. This model causes variations in the resistance and capacitance parameters of the momentum transport model as a function of the current drug concentrations in the appropriate compartments of the mass transport model. The capacitances representing the ventricles are varied in a time-dependent fashion to simulate the beat of the heart. Simulation is performed by using the Euler method to solve a system of 28 ordinary differential equations governing the momentum and mass transport models on a 32-bit microcomputer, a Macintosh II. The model was assessed by performing two demonstrations of the cardiovascular response to the vasopressor angiotensin II (AT II). They first examined the interaction between the cardiovascular system and AT II. The effect of AT II on the cardiovascular system was incorporated into the interaction model. Administration of AT II as a constant infusion (200 micrograms/hr) resulted in an elevation of mean arterial pressure from approximately 100 to 150 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II

Influence of cardiovascular diseases upon the results of the cardiovascular reflex tests in diabetic and nondiabetic subjects.

Cardiovascular reflex tests are used to assess cardiac autonomic neuropathy in diabetes mellitus. Cardiovascular diseases (CVD) are known to alter baroreflex mechanisms. Diabetic patients are at a high risk for cardiovascular complications. In order to prove whether cardiovascular diseases reduce the diagnostic value of the cardiovascular reflex tests in diabetic autonomic neuropathy unselected groups of 274 nondiabetic and 103 diabetic patients were studied: E/I, 30/15, and Valsalva ratios, sustained handgrip test and blood pressure response to standing. Both groups were subdivided into young (less than or equal to 45 years) and older (greater than 45 years) patients and into subjects with and without CVD. In young nondiabetic patients with CVD, E/I and Valsalva ratios were significantly lower than in those without CVD. In young diabetic patients with CVD, only E/I ratios were significantly reduced compared to those without CVD. The tests reflecting sympathetic nerve function did not differ between patients with and without CVD, neither in the nondiabetic nor in the diabetic subjects. In the older nondiabetic and diabetic patients, cardiovascular reflexes were generally impaired, but did not show any difference between subjects with and without CVD. In young diabetic patients suffering from CVD, the diagnostic value of cardiovascular reflex tests is reduced as far as cardiac autonomic neuropathy is concerned. In older patients, the tests are not suitable for the diagnosis of diabetic autonomic neuropathy. More specific methods are required.

Blood Pressure

Familial occurrence in cardiovascular diseases. Familial cardiovascular diseases (1).

Current knowledge and assumptions about inherited cardiovascular diseases are reported in this review. They are examined from two different points of view. In the first section (familial cardiovascular diseases) discussion will center on the main cardiovascular diseases that have a definite clinical and pathophysiological feature in which familial occurrence has been extensively demonstrated. The genetic aspects of the primary cardiomyopathies, mitral valve prolapse, arrhythmias and conduction disturbances, long QT syndromes and abnormalities of ventricular repolarization, cardiovascular malformations, coronary artery disease, essential hypertension and rheumatic fever will be examined. In the second section (cardiovascular involvement in genetic disorders) discussion will be confined to the inherited multisystem disorders involving the cardiovascular system that most frequently occur in clinical practice. Currently known cardiovascular findings in relationship to chromosomal aberrations, connective tissue disorders, metabolic and enzymatic disorders, neuromuscular disorders and other rarer syndromes will be reported.

Adult

Ethics in cardiovascular medicine. Task Force II: The relation of cardiovascular specialists to patients, other physicians and physician-owned organizations.

1. The American College of Cardiology acknowledges the continuum of changing societal, medical and economic perspectives affecting traditional medical ethics. Primacy of patient responsibility remains paramount to the cardiovascular specialist who at the same time should participate in the development of broader societal programs. 2. Medical decisions should be freely and jointly formulated by the patient and the cardiovascular specialist with appropriate sensitivity to such matters as mental competence, pertinent medical information and standards of care, sufficient time for contemplation, informed consent, patient right of refusal, physician right to refuse to provide inappropriate care and the right of patient, physician or third party payer to seek consultation or additional opinions. 3. The cardiovascular specialist should make a special effort to clarify and document patient preferences regarding end-of-life treatment through some form of advance directive. 4. The cardiovascular specialist bears a moral obligation to provide medical care to any patient who is HIV positive or has AIDS. 5. A conflict of interest occurs when a cardiovascular specialist places personal or financial interest ahead of the welfare and health of a patient. Professional accountability should be established through local or regional peer review. 6. The American College of Cardiology encourages and supports a renewed dedication to the principles of medical ethics, particularly in the field of cardiovascular disease. Cardiovascular specialists are encouraged to participate in the promulgation of medical ethics by teaching and by example, individually and with others.

Acquired Immunodeficiency Syndrome

[Cardiovascular surgery in Spain in 1988. Registry of operations of the Spanish Society of Cardiovascular Surgery].

The Spanish Society of Cardiovascular Surgery has sent a questionnaire to all 36 cardiovascular surgical groups to know the number and type of cardiovascular operations carried out in our country during 1988. The questionnaire was answered by 35 out of 36. In the year 1988, 21,438 cardiovascular patients have been operated upon and 9,053 interventions with extracorporeal circulation have been carried out: 46% in valvular disease, 36% in coronary, and 12% in congenital. The number of operations was 5,882 for vascular disease, 4,168 for valvular, 3,279 for coronary, 1,853 for congenital and 2,870 for pacemaker implantation. Comparing with other countries and specially with the Federal Republic of Germany few points in our country deserve a remarkable mention: 1) valvular pathology causes more operations than coronary one. 2) There is a low number of cardiovascular operations per million of inhabitants. 3) The cardiovascular surgical groups have a low yield. The first two points should be studied further by epidemiologists and cardiologists. To increase the yield of the cardiovascular groups it is necessary to have an adequate planning , outstanding increase of salaries and enough technological endowment.

Cardiac Surgical Procedures

Familial occurrence in cardiovascular diseases. Cardiovascular involvement in genetic disorders (2).

Current knowledge and assumptions about inheritance of cardiovascular diseases are reported in this review. They are examined from two different points of view. In the first section (familial cardiovascular diseases) discussion centered on main cardiovascular diseases with a definite clinical and pathophysiological feature in which familial occurrence has been extensively demonstrated. The genetic aspects of the primary cardiomyopathies, mitral valve prolapse, arrhythmias and conduction disturbances, long QT syndromes and abnormalities of ventricular repolarization, cardiovascular malformations, coronary artery disease, essential hypertension and rheumatic fever were examined. In this section discussion will be confined to the inherited multisystem disorders involving the cardiovascular system that most frequently occur in clinical practice. Currently known cardiovascular findings in relationship to chromosomal aberrations, connective tissue disorders, metabolic and enzymatic disorders, neuromuscular disorders and other rarer syndromes will be reported.

Cardiovascular Diseases

[Cardiovascular surgery in Spain in 1989. The Registry of Operations of the Spanish Society of Cardiovascular Surgery].

The Spanish Society of Cardiovascular Surgery has sent a questionnaire to all 36 cardiovascular surgical groups to know the number and type of cardiovascular operations carried out in our country during 1989. The questionnaire was answered by 36 out of 36. In the year 1989, 20,912 cardiovascular patients have been operated upon and 9,582 interventions with extracorporeal circulation have been carried out: 45% in valvular disease, 34% in coronary and 13% in congenital. The number of operations was 5,771 for vascular disease, 4,272 for valvular, 3,296 for coronary, 1,973 for congenital and 3,031 for pacemaker implantation. Comparing with other countries, and specially with the Federal Republic of Germany, few points in our country deserve a remarkable mention: 1) Valvular pathology causes more operations than coronary one; 2) There is a low number of cardiovascular operations per million of inhabitants; 3) The cardiovascular surgical groups have a low yield.

Cardiac Surgical Procedures

Framingham Disability Study: relationship of disability to cardiovascular risk factors among persons free of diagnosed cardiovascular disease.

The relationship between physical disability and cardiovascular risk factors among persons free of diagnosed cardiovascular disease was examined. Between 1948 and 1951, a cohort of adult, Framingham, Massachusetts, residents was assembled for a longitudinal examination of cardiovascular disease. Twenty-seven years after the participants' initial examination (between 1976 and 1978), members of the cohort who were still participating in the Framingham Heart Study were interviewed to ascertain their self-assessed ability to perform various physical activities. A score on the cumulative disability index was assigned to 2,021 persons free of diagnosed cardiovascular disease. Analyses controlled for noncardiovascular health conditions which were identified as related to disability. Among women, both long-term and current hypertension and body mass index, as well as diabetes, were associated with disability. Among men, long-term hypertension was related to disability. Age-specific analyses indicated that, for women, current hypertension was statistically significantly related to disability in the middle and oldest age groups; long-term hypertension was related to disability in the middle age group. Both long-term and current measures of diabetes in the oldest age group and long-term measure of cigarette use in the middle age group of women were also related to disability. Age-specific analyses among men indicated that the only statistically significant risk factor was long-term hypertension in the youngest age group. Cholesterol was not related to disability. Results suggest that certain cardiovascular risk factors should be considered in efforts to understand further the development of disability.

Age Factors

Relation of physical activity and cardiovascular fitness to coronary heart disease, Part II: Cardiovascular fitness and the safety and efficacy of physical activity prescription.

BACKGROUND: This paper is the second of two reports that together review the scientific evidence regarding the inverse relation between physical activity and cardiovascular fitness and coronary heart disease (CHD). METHODS: Using a MEDLINE search with the key words exercise, physical fitness, coronary heart disease, and cardiovascular disease, more than 75 articles were reviewed, evaluating study design, measurement error, bias and confounding, the strength of associations, consistency of results, temporal and dose-response relation, and biologic plausibility. RESULTS: The relative risk in epidemiologic studies comparing the least to the most fit categories ranges from 1.2 to 4.8, which is greater than that for physical inactivity. The differences between cardiovascular fitness (an attribute) and physical activity (a behavior) are highlighted. The range of correlation (r = 0.02 to 0.44) between cardiovascular fitness and physical activity is discussed relative to measurement error and genetic and environmental factors. Studies reporting the safety of regular physical activity suggest an injury rate as high as 35 injuries per 100 persons per year. Efficacy studies limited to secondary prevention trials report a 66 percent compliance rate and 15 percent reduction in total mortality. CONCLUSIONS: The scientific evidence implying a causal relation between cardiovascular fitness and CHD is strongly positive, but the clinical and public health implications are unclear. Further research and clinical guidelines are suggested.

Cardiovascular Diseases

Cardiovascular risk factors and cardiovascular death in haemodialysed diabetic patients.

In a retrospective study, causes of death and the cardiovascular risk conferred by established risk factors were analysed in 200 diabetic and 200 matched non-diabetic uraemic patients admitted for haemodialysis. Total and cardiovascular mortality was considerably higher in diabetics, both type I (4.8-fold) and type II (3.0-fold). Fifty-eight per cent of deaths in diabetics, but only 38 per cent of deaths in non-diabetics were due to cardiovascular causes; myocardial infarction and stroke accounted for less than 15 per cent of deaths, the majority being due to sudden death. Cardiovascular death in diabetes was predicted by both history of hypertension and by cardiomegaly, but to a much lesser extent by clinical evidence of macroangiopathy. The results are compatible with an important role of non-coronary cardiomyopathic mechanisms of cardiovascular death in dialysed diabetics.

Cardiovascular Diseases

Improved ascertainment of cardiovascular malformations in infants with Down's syndrome, Atlanta, 1968 through 1989. Implications for the interpretation of increasing rates of cardiovascular malformations in surveillance systems.

Several birth defects surveillance systems have shown an upward trend in the birth prevalence of several congenital cardiovascular malformations. Improvements in clinical ascertainment have been suggested as an explanation for this increase. For several decades, 40-50% of infants with Down's syndrome have been reported to have cardiac defects associated with the unbalanced genotype. Therefore, secular changes in the frequency of ascertained cardiovascular malformations among infants with Down's syndrome in surveillance systems could shed light on improvements in the ascertainment of these defects. The authors examined changes in the frequency of ascertained cardiovascular malformations among 532 cases of Down's syndrome recorded in the Metropolitan Atlanta Congenital Defects Program from 1968 through 1989. Overall, 33% of the cases have reported cardiovascular malformations. However, the frequency of these defects in Down's syndrome infants increased dramatically from about 20% in the early 1970s to more than 50% in the late 1980s (p = 0.0001). This upward trend was seen for all major categories of cardiac defects and persisted after the cases were stratified by race, sex, maternal age, hospital of birth, birth weight, and gestational age. These results show improvement in the ascertainment of cardiovascular malformations among Down's syndrome infants in a surveillance population. They are also consistent with the hypothesis that the increasing rates of cardiac defects are related, at least in part, to improved ascertainment of these defects in the population.

Down Syndrome

[Participation of the cardiovascular neurons of the bulbar cardiovascular center in the adaptive reactions of the circulatory system during changes in the composition of inspired air].

The experiments performed on rabbits have shown that with the inhalation of various gas mixtures the impulse activity of cardiovascular neurons in bulbar cardiovascular centre is changed. The most active are inserted cardiovascular neurons that are highly sensitive to O2 shortage and CO2 excess. It is believed that the experiments on Hering nerve severing indicate the possible development of reflex effects on hemodynamics during changes in inhaled gas composition produced from sinocarotid reflexogenic zone not only through bulbar respiratory neurons, but also through a system of inserted neurons of bulbar cardiovascular centre.

Adaptation, Physiological

Cardiovascular risks in psychiatric disorders and psychiatric risks in cardiovascular disorders: implications for prevention and clinical management - a large-scale umbrella review encompassing 76 meta-analyses.

OBJECTIVE: Psychiatric and cardiovascular disorders often co-occur, complicating their assessment and management. No umbrella review(UR) has summarized the meta-analytic evidence on the co-occurrence of psychiatric and cardiovascular disorders and assessed its credibility. METHODS: Meta-analytic systematic reviews of observational studies documenting the prevalence, risk factors, and outcomes associated with the co-occurrence of cardiovascular and psychiatric disorders, indexed from inception through March.16.2026, and meeting established diagnostic criteria, were included. Meta-analytic association and prevalence estimates were recalculated and graded based on established or adapted criteria. The AMSTAR-2 assessed the quality of the meta-analyses, while several subgroup analyses and meta-regressions aimed to explain the heterogeneity. RESULTS: We included 76 meta-analyses yielding 131 meta-analytic estimates. Based on pre-existing meta-analytic evidence, 22/24 prevalence estimates (91.7%) met moderate/strong credibility criteria. Strong credibility emerged for: orthostatic hypotension in Lewy body(58%;95%C.I. = 50-66%) and Alzheimer's dementias(28.0% = 95%C.I. = 17.0-40.0%); pericardial effusion in anorexia nervosa(25.0%;95%C.I. = 17.0-34.0%); in heart failure(HF): major depressive disorder(MDD)(41.9%;95%C.I. = 36.7-47.1%), mild cognitive impairment(MCI)(41.4%;95%C.I. = 38.3-45.6%), anxiety(32.0%;95%C.I. = 26.5-37.6%), MDD + anxiety(24.7%;95%C.I. = 17.9-34.3%), and dementia(19.8%;95%C.I. = 12.9-27.8%); in atrial fibrillation(AF): MCI(26.0%;95%C.I. = 21.0-30.0%), anxiety in patients undergoing pulmonary vein isolation(PVI)(25.0%;95%C.I. = 12.0-46.0%), MDD in PVI patients (20.0%;95%C.I. = 13.0-29.0%); in coronary artery disease: MDD + anxiety(19.8%;95%C.I. = 16.0-24.6%): in schizophrenia spectrum disorders: clozapine-associated-cardiomyopathy(0.6%;95%C.I. = 0.2-2.3%); clozapine-associated-cardiomyopathy absolute death rates (0.0003;95%C.I. = 0.0001-0.0012); clozapine-associated-cardiomyopathy case fatality rate (0.078;95%C.I. = 0.018-0.285). Several additional disorders were multimorbid in>5% of people, yet with a lower credibility rating. No re-pooled risk factors/outcomes reached strong credibility criteria. CONCLUSIONS: The present study provides an atlas of cardiovascular and psychiatric multimorbidity across varying levels of credibility, reinforcing the need for an integrated, multidisciplinary approach to patient care and for more research on actionable risk/protective factors and outcomes.

Humans