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PubMed1995

Vascular selective calcium entry blockers in the treatment of cardiovascular disorders: focus on felodipine.

Calcium entry through L-type calcium channels is essential for contraction of both arterial smooth muscle and the myocardium, and is important in cardiac conduction. First-generation calcium entry blockers lack or have a modest degree of vascular selectivity and inhibit cardiac function at doses producing therapeutic arterial dilatation. Such agents may cause deterioration in patients with left ventricular dysfunction, and their combination with a beta-adrenergic blocker may adversely affect cardiac contractility and conduction. Development of newer agents has focused on obtaining a higher degree of vascular selectivity. Felodipine is a highly vascular selective calcium entry blocker, with a vascular selectivity ratio greater than 100, as shown experimentally. Isradipine and nicardipine are also vascularly selective calcium entry blockers. Hemodynamic studies in patients with hypertension, coronary artery disease, congestive heart failure, or in patients receiving beta-adrenergic blockade, show that felodipine can produce profound arteriolar dilatation without the negative effects of left ventricular systolic performance. Furthermore, felodipine alone or when added to a beta-adrenergic blocker does not interfere with cardiac conduction. The primary mechanism that accounts for the efficacy of dihydropyridine calcium entry blockers in hypertension and angina pectoris is arterial dilation, whereas nondihydropyridines may also derive part of their effect from inhibition of cardiac performance. As some of these patients, most commonly the elderly, have concomitant left ventricular dysfunction, it should be advantageous to avoid myocardial depression in the treatment of their primary disease. Preliminary studies in patients with heart failure indicate that felodipine and amlopidine may improve hemodynamics, reduce neurohormonal activation, and increase exercise tolerance, but final conclusions must await the randomized clinical trials now underway.

Amlodipine↗
PubMed2004

Single vs multivessel treatment during primary angioplasty: results of the multicentre randomised HEpacoat for cuLPrit or multivessel stenting for Acute Myocardial Infarction (HELP AMI) Study.

DESIGN: Prospective randomized, multicentre study. RATIONALE: Recanalisation of the culprit lesion is the main goal of primary angioplasty for acute myocardial infarction. With the exception of cardiogenic shock, staged procedures are performed in the presence of multivessel disease. The study hypothesis is that with modern non-thrombogenic stents (heparin coated) complete revascularization with multivessel treatment can be safely achieved during the primary angioplasty procedure with a lower need of subsequent revascularization procedures and at a lower cost. ENDPOINTS: PRIMARY: 12-month incidence of repeat revascularization (any revascularization, infarct related artery as well as non-infarct-related artery). SECONDARY: (1) in hospital repeat revascularization, reinfarction and death; (2) total hospital cost (including a 12 months follow-up period). METHODS: 69 patients with ST elevation Acute Myocardial Infarction (AMI), <12 hours after symptoms onset, undergoing primary angioplasty, with documented multivessel disease and both culprit lesion and 1 to 3 other lesions suitable for stent implantation. Unbalanced randomization between culprit lesion treatment only (n = 17) and complete multivessel treatment (n = 52, with 71 additional lesions treated). RESULTS: The two groups were well balanced in terms of clinical characteristics, number of diseased vessels and angiographic characteristics of the culprit lesion. In the complete multivessel treatment group 2.36 +/- 0.64 lesions per patient were treated using 2.73 +/- 0.78 heparin coated stents (1.00 lesions and 1.29 +/- 0.61 stents in the culprit treatment group, both p < 0.001). The duration of the procedure increased from 53 +/- 21 min (culprit treatment group) to 69 +/- 32 min (p = 0.032) and the amount of contrast used from 242 +/- 102 ml (culprit treatment group) to 341 +/- 163 ml (multivessel complete treatment), p = 0.025. A similar low incidence of in-hospital major adverse cardiac events was observed in the 2 groups (0 and 3.8% in culprit and multivessel treatment groups, p = 0.164). The increase in the incidence of new revascularisation in the culprit treatment group at 12 month follow-up was not significant (35 vs 17%, p = 0.247) but was sufficient to compensate the initial higher in-hospital cost, with a similar 12 month hospital cost in the 2 groups (Euro 22,330 +/- Euro 13,653 vs Euro 20,382 +/- Euro 11,671, p = 0.231). CONCLUSION: Multivessel treatment during primary PTCA was safe in this controlled trial. However, when only the culprit lesion was initially treated, the need for subsequent clinically driven revascularization remained low and no clinical or economical advantages were obtainable with a more aggressive initial approach. In clinical practice, a staged approach to multivessel treatment during primary angioplasty avoids to treat unnecessarily non clinically relevant lesions.

Aged↗
PubMed2001

[New concepts of primary prevention require rethinking].

The decline in cardiovascular mortality over the past decades is due to improved survival of patients with clinical events rather than to a declining incidence of these events. As a result, an increased prevalence of chronic coronary artery disease and especially congestive heart failure has been described. Further substantial reductions in coronary artery disease morbidity and mortality can only be anticipated if coronary artery disease is treated before the manifestation of clinical disease. Modern concepts of primary prevention incorporate an individualized approach to risk assessment. Medical history, physical examination, and established laboratory tests are the basic instruments which allow for quantitative risk assessment. Tables and simplified algorithms derived from large clinical trials enable the calculation of intermediate and long-term ("life-time") probability of cardiac events. In this setting of quantitative risk assessment, the importance of some risk factors is increasingly recognized, namely diabetes. Noninvasive diagnostic testing is used to detect preclinical atherosclerotic plaque disease. Direct imaging of coronary and peripheral arteries, the ankle-brachial index, and measurements of C-reactive protein represent novel methods which have become available for further risk stratification. Because they consider the pathophysiology of atherosclerosis and coronary artery disease, these methods may facilitate decision-making regarding preventive treatment in patients who have an intermediate risk on the basis of the traditional risk factors. The modern concept of primary prevention is aimed at identifying subjects whose risk is similarly high as that of patients with clinically established cardiovascular disease. These subjects can then be treated efficiently, and the strict distinction between primary and secondary prevention is blurred.

Coronary Artery Disease↗
PubMed2002

The association of seropositivity to Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus with risk of cardiovascular disease: a prospective study.

OBJECTIVES: We sought to determine whether seropositivity to Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus (CMV) is an independent predictor of incident cardiovascular disease. BACKGROUND: Recent reports have suggested that infections may contribute to risk of cardiovascular disease. However, prospective studies of these associations in a free-living population are lacking. METHODS: We measured serum H. pylori IgG, C. pneumoniae IgG and IgA, and CMV IgG levels in Framingham Heart Study cohort participants. Blood samples were drawn during the 16th biennial examination cycle (1979 to 1982) from 1,187 participants free of cardiovascular disease (mean age 69 years) and stored at -20 degrees C. A pooled primary end point of myocardial infarction, atherothrombotic stroke, and coronary heart disease deaths was studied in relation to serology. Using a Cox model, hazard ratios (HR) and 95% confidence intervals (CI) were calculated, adjusting for age, gender, and established risk factors. RESULTS: Seropositivity to H. pylori IgG, C. pneumoniae IgG, C. pneumoniae IgA, and CMV IgG was 60%, 45%, 11%, and 69%, respectively. During 10 years of follow-up, incident cardiovascular disease occurred in 199 participants (16.8%). In age- and gender-adjusted models, H. pylori IgG (HR 1.09, 95% CI 0.81 to 1.46), C. pneumoniae IgG (HR 0.91, 95% CI 0.68 to 1.20), C. pneumoniae IgA (HR 0.65, 95% CI 0.39 to 1.07), and CMV IgG (HR 0.84, 95% CI 0.62 to 1.12) were not associated with incident cardiovascular disease. These associations were further attenuated after adjustment for risk factors including body mass index, total and high-density lipoprotein cholesterol, diabetes mellitus, smoking, and hypertension. These estimates did not change for the individual components of cardiovascular disease, and seropositivity to more than one organism did not alter these risk estimates substantially. CONCLUSIONS: In this elderly cohort, chronic H. pylori, C. pneumoniae, and CMV infections, as evidenced by seropositivity, were not associated with increased risk for cardiovascular disease. Additional studies are needed to determine the relations of chronic infections to cardiovascular disease risk in younger persons.

Aged↗
PubMed2003

Thrombosis in pediatric cardiac patients.

Cardiac disease and thrombosis are intimately related in adults, but primary myocardial infarction in children is rare. Homozygous familial hyperlipidemia occurs in approximately 1 million children, and causes severe coronary artery disease during childhood. Kawasaki's disease is an acquired inflammatory disorder, which, if untreated, leads to coronary artery aneurysms and subsequent myocardial infarction. The current understanding of the pathophysiology and management of these conditions is discussed. More commonly, the relationship between cardiac disease in children and thrombosis is that children being treated for congenital structural cardiac disease develop iatrogenic thrombosis, most commonly precipitated by central venous access. The epidemiology of common treatment-induced thrombosis is described, and management guidelines presented. Finally, many cardiac surgical procedures increase the risk of thrombosis, and prophylactic antithrombotic therapy is commonly used. The current evidence for prophylaxis in different clinical situations is presented. Additional study is required in all areas to improve the outcome for children affected by cardiac disease and thrombosis.

Anticoagulants↗
PubMed1990

Treatment of heart failure in the elderly.

Heart failure is a syndrome of breathlessness, fatigue and oedema. The effects of ageing on myocardial function and the prevalence of often multiple cardiac pathologies makes heart failure a disease of the elderly, usually characterized by primary or secondary myocardial systolic dysfunction. Appropriate treatment, which requires precise diagnosis, involves correction of precipitating or aggravating factors and the rational use of drug therapy. Diuretics and ACE inhibitors offer a combination of both symptom control and improvement in prognosis. Other agents such as digoxin, xamoterol and nitrates may be particularly useful in the treatment of patients with associated problems such as atrial fibrillation and angina. Because both ageing and heart failure may alter pharmacokinetics and pharmacodynamics, safe and effective treatment of heart failure in the elderly requires understanding of the clinical pharmacology of the drugs used.

Aged↗
PubMed1997

Resting Tl-201 scintigraphy in the evaluation of myocardial sarcoidosis.

In patients with sarcoidosis, myocardial involvement is common and may be fatal. With extensive disease, the primary manifestations may include conduction abnormalities and arrhythmias, which may lead to sudden death. Myocardial perfusion scintigraphy may be the most accurate method to assess extent of myocardial involvement and response to therapy.

Aged↗
PubMed1993

[Chagas disease and primary arterial hypertension].

PURPOSE: To evaluate the pressoric behaviour in chagasic patients in different stages of myocardial damage and to correlate Chagas' disease with arterial hypertension. METHODS: The arterial blood pressure of 644 chagasic patients surveyed in the HC-UNICAMP, with arterial hypertension or not, associated with the stage of myocardial dysfunction was evaluated. This group was compared with 370 hypertensive patients without Chagas' disease. Both were divided by sex and age. The results were evaluated by covariance analysis and the significance was pointed at p < 0.05. RESULTS: The chagasic group presented a high prevalence of arterial hypertension with 16.8% in the clinical phase I, 27.8% in the phase II and 34% in the III. Both hypertensive and nonhypertensive chagasic patients had a significant drop in clinical phase I after the age of 30 years. The chagasic patients classified in phase II presented a high prevalence between 30-50 years, not associated with the pressoric behaviour and/or sex. The symptomatic myocardial dysfunction (phase III) was uncommon below 40 years old in chagasic group with hypertension or not, but presented a highest prevalence in male hypertensive chagasic patients above 50 years old. CONCLUSION: The study demonstrated a more usual association of Chagas' disease and hypertension in patients with symptomatic myocardial dysfunction, above 50 years old. This find evidenciates the somatory and progressive effect of both diseases. It is possible that the pathogenic mechanisms of Chagas' disease contributed to the increment of the arterial blood pressure.

Adult↗
PubMed2003

Metabolic therapy in the treatment of ischaemic heart disease: the pharmacology of trimetazidine.

The primary result of myocardial ischaemia is reduced oxygen consumption and adenosine triphosphate (ATP) formation in the mitochondria, and accelerated anaerobic glycolysis, lactate accumulation and cell acidosis. Classic pharmacotherapy for demand-induced ischaemia is aimed at restoring the balance between ATP synthesis and breakdown by increasing the oxygen delivery (i.e. with long acting nitrates or Ca2+ channel antagonist) or by decreasing cardiac power by reducing blood pressure and heart rate (i.e. with beta-blocker or Ca2+ channel antagonist). Animal studies show that fatty acids are the primary mitochondrial substrate during moderate severity myocardial ischaemia, and that they inhibit the oxidation of carbohydrate and drive the conversion of pyruvate to lactate. Drugs that partially inhibit myocardial fatty acid oxidation increase carbohydrate oxidation, which results in reduced lactate production and a higher cell pH during ischaemia. Trimetazidine (1-[2,3,4-trimethoxibenzyl]-piperazine) is the first and only registered drug in this class, and is available in over 90 countries world-wide. Trimetazidine selectively inhibits the fatty acid beta-oxidation enzyme 3-keto-acyl-CoA dehydrogenase (3-KAT), and is devoid of any direct haemodynamic effects. In double-blind placebo-controlled trials trimetazidine significantly improved symptom-limited exercise performance in stable angina patients when used either as monotherapy or in combination with beta-blockers or Ca2+ channel antagonists. Given available evidence, trimetazidine is an excellent alternative to classic haemodynamic agents, and is unique in its ability to reduce symptoms of angina when used in patients resistant to a haemodynamic treatment as vasodilators, beta-blockers or Ca2+ channel antagonists.

Angina Pectoris↗
PubMed2004

Effectiveness of percutaneous coronary interventions in nonagenarians.

Data on percutaneous coronary intervention (PCI) in nonagenarians are very scarce. The investigators present a series of 26 nonagenarians who underwent PCI (29 lesions, 1.1 +/- 0.3 per patient). Most (96%) had acute coronary syndrome at presentation, 27% underwent primary PCI for acute myocardial infarctions, and 54% had multivessel disease. Angiographically successful results were obtained in 24 patients (92%), and coronary stents were used in 81%. Five patients (19%) died during hospitalization. In-hospital mortality was significantly greater in patients with Killip class III or IV at presentation (100% vs 9%, p = 0.001), in those in whom the procedure was a primary PCI for acute myocardial infarction (57% vs 5%, p = 0.010), and in the presence of angiographic failure (100% vs 13%, p = 0.031). In-hospital mortality was 0% after excluding patients in cardiogenic shock and those with primary PCI. Thus, most nonagenarians who undergo PCI have a high-risk profile. However, PCI achieves a successful angiographic result in most patients. Mortality is high but concentrated in patients in cardiogenic shock and with primary angioplasty as PCI.

Aged↗
PubMed2003

[Prevalence and management of patients with a prior history of atherothrombotic disease in primary care in France. Results of the ECLAT1 survey].

This cross-sectional study assessed the prevalence of subjects with a previous history of atherothrombotic disease (myocardial infarction, ischemic stroke and/or lower limb arterial disease) among patients treated in general medicine. A random sample of 3,009 French general practitioners was recruited. Patients who consulted one of these general practitioners on December 7th 2000 were included. Those with a previous history of atherothrombotic disease were identified and further data on their cardiovascular risk factors and drug use were collected. The prevalence of patients with a previous history of atherothrombotic disease was 2% [95% confidence interval: 1.9-2-1] in subjects younger than 65, 13.4% [12.7-14.2] between 65 and 74 and 17.0% [16.2-17.8] in subjects older than 74. Arterial hypertension was found in 62.2% of the patients with a previous history of atherothrombotic disease, overweight or obesity in 59.4%, hypercholesterolaemia in 55%, current or past smoking in 48.3%, and diabetes mellitus in 20.1%. The last blood pressure and LDL-cholesterol measurements were respectively higher than or equal to 140/90 mmHg and 3 mmol/l in 70.6% of the patients suffering from arterial hypertension (missing data in 2.2%) and in 48.2% of the patients suffering from hypercholesterolaemia (missing data in 31.4%). Atherothrombosis represents a significant part of the primary care activity in France. Despite a widespread antihypertensive and hypocholesterolaemic drug prescription, the control of cardiovascular risk factors is insufficient. The high prevalence of overweight may contribute to this poor control.

Adult↗
PubMed1989

Heart disease in systemic sclerosis.

Primary cardiovascular manifestations of SSc include pericardial disease, myocardial disease, conduction abnormalities, and cardiac arrhythmias. Significant cardiac abnormalities are present in more than half of SSc patients at autopsy. As the frequency of subclinical cardiac involvement is now appreciated and noninvasive cardiac diagnostic modalities continue to improve, the ability to detect early asymptomatic involvement in SSc has improved. Two-dimensional echocardiography, radionucleotide imaging, and ambulatory ECG allow recurrent serial testing with virtually no morbidity. The current treatment of cardiac involvement in SSc is emperic and primarily directed at symptomatology. Large prospective randomized trials are needed to determine if preventive therapy is effective. With the advent of new immunological and cardiotropic agents and a better understanding of the primary disease process, our ability to alter the pathogenesis and final outcome of cardiac involvement in SSc should improve.

Arrhythmias, Cardiac↗
PubMed2001

A common mutation in the gene for coagulation factor XIII-A (VAL34Leu): a risk factor for primary intracerebral hemorrhage is protective against atherothrombotic diseases.

The role of a common polymorphism in the factor XIII A-subunit gene (FXIII Val34Leu) has been recently investigated as a protective genetic factor against arterial and venous thrombosis. In addition, the less frequent Leu34 allele has been described as a risk factor for intracerebral hemorrhage. We evaluated the prevalence of this polymorphism by PCR in three case-control studies of patients diagnosed as having primary intracerebral hemorrhage (PCH, n = 130), coronary heart diseases (CHD, n = 240; myocardial infarction/no myocardial infarction, 120/120), and cerebrovascular diseases (CVD, n = 240; cerebral infarction/transient ischaemic attack, 120/120). The matched control groups consisted of patients admitted to the hospital without history of vascular disease. In addition, 200 healthy subjects were investigated. The frequency of the mutated allele (Leu34) was higher in patients with PCH than in controls (33.8% vs. 23.1%, P = 0.009) and lower in CHD and CVD patients compared to controls (18.1% vs. 25.2%, P = 0.010 and 17.3% vs. 24.2%, P = 0.011, respectively). Moreover, among the patients with CHD, the Leu34 allele was underrepresented in cases with myocardial infarction than without (12.9% vs. 23.3%, P = 0.004) and than in controls (12.9% vs. 25.2%, P < 0.001). Similar findings were obtained in patients with CVD comparing the cases with cerebral infarction versus cases with transient ischaemic attack (12.5% vs. 22.1%, P = 0.008) and versus controls (12.5% vs. 24.2%, P < 0.001). Finally, considering altogether the groups of ischaemic patients (CHD and CVD, n = 480), it was noted a trend towards a higher mean age of the clinical onset in homozygotes for the Leu allele than in the wild types (P = 0.078). This study indicates that in our population possession of the FXIII Val34Leu mutation predisposes to the occurrence of primary intracerebral hemorrhage and protects against cerebral and myocardial infarction. A wider modulatory role in the progression and onset of atherothrombotic diseases could be ascribed to FXIII Val34Leu.

Age of Onset↗
PubMed1981

Primary heart disease in systemic sclerosis (scleroderma): advances in clinical and pathologic features, pathogenesis, and new therapeutic approaches.

Heart disease in SSCL may be primary or secondary. Primary involvement includes pericarditis, myocardial fibrosis, and contraction band necrosis with congestive cardiomyopathy, conduction system fibrosis, intramural coronary artery lesions and, rarely, valvular disease. Symptoms include those of left and right ventricular failure, chest pain, palpitations, syncope, and sudden death. Pathogenesis may be related to functional Raynaud's phenomenon of the heart and/or structural small vessel disease. Therapy at present is symptomatic; however, new therapeutic approaches are warranted.

Coronary Vessels↗
PubMed1995

Cost effectiveness of thrombolytic therapy with tissue plasminogen activator as compared with streptokinase for acute myocardial infarction.

BACKGROUND: Patients with acute myocardial infarction who were treated with accelerated tissue plasminogen activator (t-PA) (given over a period of 1 1/2 hours rather than the conventional 3 hours, and with two thirds of the dose given in the first 30 minutes) had a 30-day mortality that was 15 percent lower than that of patients treated with streptokinase in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) study. This was equivalent to an absolute decrease of 1 percent in 30-day mortality. We sought to assess whether the use of t-PA, as compared with streptokinase, is cost effective. METHODS: Our primary, or base-case, analysis of cost effectiveness used data from the GUSTO study and life expectancy projected on the basis of the records of survivors of myocardial infarction in the Duke Cardiovascular Disease Database. In the primary analysis, we assumed that there were no additional treatment costs due to the use of t-PA after the first year and that the comparative survival benefit of t-PA was still evident one year after enrollment. RESULTS: One year after enrollment, patients who received t-PA had both higher costs ($2,845) and a higher survival rate (an increase of 1.1 percent, or 11 per 1000 patients treated) than streptokinase-treated patients. On the basis of the projected life expectancy of each treatment group, the incremental cost-effectiveness ratio--with both future costs and benefits discounted at 5 percent per year--was $32,678 per year of life saved. The use of t-PA was least cost effective in younger patients and most cost effective in older patients. At all ages, the use of t-PA in patients with anterior infarctions yielded more favorable cost-effectiveness values. In our secondary analyses, the cost-effectiveness values were most sensitive to a lowering of the projected long-term survival benefits of t-PA and to moderate or greater increases in the projected medical costs for patients in the t-PA group after the first year. In contrast, our results were not sensitive to even very unfavorable assumptions about the additional costs associated with the higher rate of disabling stroke that was noted in patients treated with t-PA in the GUSTO study. CONCLUSIONS: The cost effectiveness of treatment with accelerated t-PA rather than streptokinase compares favorably with that of other therapies whose added medical benefit for dollars spent is judged by society to be worthwhile.

Adult↗
PubMed2006

Codon 54 polymorphism of the fatty acid binding protein (FABP) 2 gene is associated with increased cardiovascular risk in the dyslipidemic diabetic participants of the Veterans Affairs HDL intervention trial (VA-HIT).

The threonine (Thr) for alanine (Ala) codon 54 polymorphism of the fatty acid binding protein (FABP) 2 gene, when compared to the wild type, is associated with dyslipidemia. Since dyslipidemia is common in diabetes and is associated with increased cardiovascular risk, we tested the hypothesis that Thr-54 is associated with increased cardiovascular risk in patients with diabetes. The secondary prevention veterans affairs HDL intervention trial (VA-HIT) was carried out in patients with dyslipidemia. The DNA of trial participants (n=776) was screened for the Thr-54 polymorphism and cardiovascular endpoints were monitored. The polymorphism was detected in 370 (47.7%). For first occurrence of the primary endpoint [myocardial infarction (MI) or coronary heart disease (CHD) death] the hazard ratio (HR) and confidence intervals (Cox proportional hazards model) was 2.5 (1.2, 5.3) p=.02 in diabetic carriers of Thr-54 versus carriers without diabetes or fasting glucose >7 mmol/L. For the expanded endpoint (stroke, MI or CHD death), the corresponding HR was 3.0 (1.4, 5.4) p=.0003 and for the stroke alone the corresponding HR was 3.5 (1.4-8.9) p=.01. The higher cumulative incidence of the expanded endpoint in diabetic participants carrying the FABP2 polymorphism versus non-diabetic carriers was consistently present throughout the 5 years of the study (p=.0002). We conclude that based on the VA-HIT data, the Thr-54 polymorphism of the FABP2 gene is associated with a 2-3.5-fold increase in cardiovascular risk in dyslipidemic men with diabetes compared to their non-diabetic counterparts.

Aged↗