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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To date, lipid-lowering therapy appears to be the most effective medical intervention to retard progression of coronary atherosclerosis. In spite of promising experimental results, clinical trials completed so far have failed to demonstrate that calcium channel blockers (CCBs) alone influence the evolution of established coronary atherosclerosis. To assess whether the two therapies may have an additive or synergistic beneficial effect on human atherosclerosis, we reviewed in this regard the data of the angiographic Regression Growth Evaluation Statin Study (REGRESS) trial. REGRESS was designed to determine the effect of lipid-lowering therapy with pravastatin in symptomatic patients with normal to moderately raised cholesterol levels. Angiographically, with respect to the minimum obstruction diameter, in the pravastatin group, patients had on average 0.05 mm (95% confidence interval [CI]: 0.01-0.09) less progression if cotreated with CCBs compared with no CCB treatment, whereas in the placebo (no pravastatin) group, no effect of CCB treatment was observed (interaction test for differential effect of CCB treatment in patients with pravastatin compared with patients receiving placebo: P=.0016). With respect to the mean segment diameter, similar although not significant (P=.33) results were found. With respect to new lesion formation, in the pravastatin group, there were 50% (CI: 25-83) fewer patients with new angiographic lesions if cotreated with CCBs compared with no CCB cotreatment, whereas in the placebo (no pravastatin) group, no significant effect of CCB treatment was observed (interaction test: P=.0026). No beneficial effects of CCB treatment on clinical events were observed. Although the REGRESS trial was not designed to evaluate combination therapy, the results suggest strongly that addition of CCBs to 3-hydroxy-3-methyl-glutaryl-coenzyme reductase inhibitor therapy (pravastatin) acts synergistically in retarding the progression of established coronary atherosclerosis.
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PMID:Evidence for a synergistic effect of calcium channel blockers with lipid-lowering therapy in retarding progression of coronary atherosclerosis in symptomatic patients with normal to moderately raised cholesterol levels. The REGRESS Study Group. 863 Jun 69

Hypertension is not solely a phenomenon of elevation of systemic blood pressure. It frequently occurs in association with a great deal of metabolic derangement's and should never be regarded as coincidental only. Furthermore, a knowledge of these metabolic derangements may provide a clue to unveil the underlying mechanisms how essential hypertension and its associated complications arise. Therefore we devoted our attention to platelet dysfunction and dyslipidemia which are closely associated with atherosclerosis-the commonest complication of hypertension. We found there exists enhanced platelet aggregation in essential hypertension and a variety of its associated atherosclerotic diseases. Such an aberration in platelet function may be modified after administration of antihypertensive medications such as angiotensin converting enzyme (ACE) inhibitors, calcium channel blockades, beta blockades and dietary manipulation. We also demonstrated the close association between hypertension and its associated atherosclerotic complications and abnormal lipids profile. Hypertriglyceridemia which was initially regarded unimportant in the pathogenesis of atherosclerosis is found to be closely related to hypertension. In an intensive review, we found that people in Taiwan has experienced a huge increase in dietary calories and total fat consumption. In order to solve this emerging problem, a national guideline for diagnosis and management of lipid disorders in Taiwan was developed and announced. Through these efforts, we hope we can reduce the cardiovascular morbidity and mortality in Taiwan and even extend our experience to other countries.
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PMID:Thrombogenic and lipid risk factors in hypertension and coronary artery disease. 868 58

Hypertension should be detected and treated early in diabetic patients. It has a marked contribution to the morbidity and mortality of diabetic individuals due to both atherosclerosis and microvascular disease. Antihypertensive treatment is an effective tool in slowing the progression of early and advanced diabetic nephropathy. Prospective studies addressing the effects of antihypertensive regimens on the incidence of CHF, stroke, and coronary artery disease in the diabetic population are not available. We assume that the beneficial effects of therapy apply to both diabetic and nondiabetic subjects. Glycemic control and the lipid profile are major concerns when selecting an antihypertensive drug. Because hyperinsulinemia and insulin resistance have been advocated as hypertensive and atherosclerotic risk factors, the effects of antihypertensive drugs on insulin action and plasma insulin levels may also become an important element in the selection of an antihypertensive agent. ACE inhibitors, calcium channel blockers, and alpha-adrenergic blockers probably offer the most favorable metabolic profile when compared with diuretics and beta-blockers and should be used as the initial drugs in most clinical settings.
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PMID:Hypertension in diabetes mellitus. 879 6

Previous studies have shown that the administration of certain calcium channel blocking drugs (at an appropriate time point) can reduce the severity of atherosclerotic lesion formation. This study was undertaken to determine if the administration of isradipine would reverse established lesions produced by feeding rabbits an atherogenic diet. Rabbits were fed cholesterol for three weeks and examined directly, or after being left for a four week washout period, with or without a daily oral supplement of isradipine. Fatty streaks were well established after three weeks of cholesterol feeding and were more extensive at the end of the washout period, as indicated by gross changes in the volume of the intima per unit length of aorta. When isradipine was administered during the washout period, the volume of the intima per unit length of aorta fell to levels below those produced by cholesterol feeding for three weeks alone. The major components of the lesions affected to accommodate these changes were the foam cells and myointimal cells; these were examined in detail using morphometry and lipid cytochemistry. The mean volume of intima/cm of aorta occupied by foam cells and myointimal cells both fell by more than 60% to levels lower than those found after three weeks of cholesterol feeding alone. The volume of the extracellular space of the intima occupied by cytochemically demonstrable unesterified and esterified cholesterol was reduced by isradipine administration as was that of foam cells, all to levels lower than those found after three weeks of cholesterol feeding alone. These data indicate that the administration of isradipine during a washout period, after cholesterol feeding, can promote the regression of fatty streak lesions.
Atherosclerosis 1996 Jan 26
PMID:The effect of isradipine administration on existing fatty streaks in the cholesterol-fed rabbit: a morphometric study. 880 1

Diabetes mellitus is a complex group of diseases that has hyperglycemia as a common metabolic abnormality. Although it is well-known that diabetic patients are susceptible to the effects of large vessel atherosclerosis with specific cardiac and cerebral complications, the association of diabetes mellitus with cardiac dysfunction caused by cardiomyopathy in the absence of significant coronary artery disease has been recognized for many years. However, the pathogenesis of diabetic cardiomyopathy remains unknown and has been somewhat controversial. Specifically, whether diabetes mellitus with its metabolic effects is sufficient to account for cardiomyopathy remains to be proven. This paper reviews the evidence for and against a metabolic etiology. In addition, we review the clinical and experimental evidence that supports the view that diabetes mellitus acts together with hypertension to produce structural damage in the heart that manifests as ventricular dysfunction and ultimately congestive heart failure. The concomitant effects of the metabolic derangements of diabetes and the vascular abnormalities associated with hypertension may lead to microvascular-induced tissue injury. Findings supporting this hypothesis are presented, along with observations suggesting that treatment with vasodilating calcium channel blockers or angiotensin converting enzyme inhibitors may be beneficial in regard to tissue pathology and mortality in experimental models. Recent clinical studies also support a role for the microcirculation in diabetics. Finally, it is suggested that if the microcirculation is pathogenetically involved in diabetic cardiomyopathy, then agents that improve microcirculatory flow along with tight control of hypertension may be as beneficial in the treatment or prevention of diabetic cardiomyopathy as strict metabolic control of hyperglycemia.
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PMID:Myocardial alterations in diabetes and hypertension. 886 52

During inflammatory disorders, some proteases and very reactive oxygen metabolites are produced by activated phagocytic cells. These proteases and oxidants are involved in many diseases like tissue injury or atherosclerosis. It was shown in vitro that diltiazem, a calcium channel blocker, had antielastase and antioxidant properties. This drug inhibited the release of elastase by neutrophils in a dose dependent manner when these cells were stimulated by phorbol-myristate-acetate (PMA) or by formyl-methionyl-leucylphenylalanine (fMLP) with an IC50 of 144.5 microM, and 132.8 microM, respectively. Towards the oxidants, the 50% inhibitory concentrations (IC50) of diltiazem are 422 microM, 138 microM and 165 microM for superoxide anion, hypochlorous acid and hydroxyl radical production by PMA stimulated human neutrophils, respectively. In the case of fMLP stimulated human neutrophils, the IC50 for superoxide anion is 78 microM. When human neutrophils were stimulated by dioctanoylglycerol (DiC8) or by calcium ionophore (Ca.I), the IC50 for superoxide anion were 175.5 microM and 186 microM, respectively. When human neutrophils were stimulated by opsonized zymosan (OZ), diltiazem did not show an inhibition of superoxide production in a dose dependent manner. This drug did not act by scavenging elastase or oxidants as demonstrated by cell free models. A mechanism of elastase and oxygen metabolites inhibition by diltiazem has been considered specially toward the mobilization of cytosolic calcium and an inhibition of protein kinase C cannot be excluded. The results suggest that diltiazem might contribute to attenuate the development and the progression of atheroma where oxidants and elastase have been implicated.
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PMID:Effects of calcium antagonist diltiazem on leukocyte elastase and on reactive oxygen species production in human neutrophils. 887 26

Previous studies have shown that calcium channel blockers may reduce the development of experimental atherosclerosis, and that nifedipine may slow the progression of coronary atherosclerosis in humans. The mechanisms responsible for this antiatherogenic effect are still unclear. It has been recently proposed that oxygen free radicals can induce the oxidation of human low-density lipoproteins (LDL) and that oxidized LDL may be an atherogenic stimulus. Previous studies in other systems have shown that calcium channel blockers may effectively inhibit oxygen radical-induced lipid peroxidation in vitro. Thus, the aim of the present study was to investigate whether calcium channel blockers may also reduce LDL modifications induced by oxygen radicals. Isolated human LDL were exposed to oxygen radicals generated by CuSO4 (10 microM for 18 hours) after a 30 minute pre-incubation with different concentrations (1-100 microM) of nifedipine, diltiazem, and verapamil. Lipid peroxidation was measured from malonyldihaldehyde (MDA) production. Oxygen radical-induced damage on apolipoprotein-B100 was evaluated by acrylamide and agarose gel electrophoresis. Calcium channel blockers dose-dependently prevented oxidation of both the lipid and protein components of LDL. MDA formation was reduced in LDL pre-incubated with calcium antagonists before exposure to oxygen radicals (% MDA inhibition was 89.8 +/- 6.9 with 30 microM nifedipine, 68.6 +/- 4.9 with 30 microM verapamil, and 65.6 +/- 7.1 with 30 microM diltiazem; p < 0.01 vs. controls). Similarly, apolipoprotein-B100 integrity was preserved against oxygen radical attack in the presence of calcium antagonists. Thus, calcium channel blockers reduce the oxidation of human LDL in vitro. These data suggest that reduced formation of atherogenic oxidized LDL may be an additional mechanism for the antiatherosclerotic effects of calcium channel blockers in vivo.
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PMID:Calcium-channel blockers inhibit human low-density lipoprotein oxidation by oxygen radicals. 892 55

Outcomes research seeks to identify effective evidence-based methods of providing the best medical care. While randomized clinical trials (RCT) usually provide the clearest answers, they are often not done or not practicable. More than a decade after the introduction of calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors, clinical trial data about their effect on major disease endpoints in patients with hypertension are still not available. The primary alternatives are the use of randomized trials that include surrogate endpoints, such as level of blood pressure or extent of carotid atherosclerosis, and the use of observational studies that include major disease endpoints. Both approaches, their strengths and limitations, are discussed in detail. The possibility of residual confounding limits the strength of inferences that can be drawn from observational studies. Similarly, the possibility of important drug effects, other than those involving the surrogate endpoint, limits the inferences that can be drawn from randomized trials that rely solely on surrogate outcomes as guides to therapy. In the absence of evidence from large clinical trials that include major disease endpoints, treatment decisions and guidelines need to synthesize the best available information from a variety of sources. Consistency of findings across various study designs, outcomes, and populations is critical to the practice of evidence-based medicine and the effort to maximize the health benefits of antihypertensive therapies.
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PMID:Hypertension and outcomes research. From clinical trials to clinical epidemiology. 892 68

Arterial hypertension is the most frequent cardiovascular complication of diabetes mellitus. Diabetes mellitus-type-1 occurs in about 30% of patients and it is connected to development of diabetic nephropathy, while type-2 occurs in as much as 70% of cases, having fast atherosclerosis as a base in its etiopathogenesis. The therapy of arterial hypertension in diabetic patients is specific and in some ways different depending on the type of diabetes mellitus as well as other complications characteristic for diabetes. Apart from drug therapy, it includes: body weight reduction in obese patients, restriction of sodium chloride, proteins and alcohol drinking, as well as other risk factors (smoking, for example). Drug therapy means application of different groups of antihypertensive agents (selective beta-blockers, diuretics, angiotensin-converting enzyme inhibitors, calcium channel antagonists and postsynaptic alpha-1 blockers). Some of them have adverse effects on metabolism of lipids, while some have other adverse effects which must be taken into account when determining therapy. However, angiotensin-converting enzyme inhibitors and calcium channel antagonists are the most preferred today as the most effective and with least adverse effects.
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PMID:[Modern principles of therapy of hypertension in diabetic patients]. 892 53

We compared the effect of two different calcium channel blockers (CCB), Nifedipine (1,4-dihydropyridine calcium antagonist) and Diltiazem (a benzothiazepine agent) on plasma components and the development of atherosclerotic plaque in experimental hypercholesterolemia. Golden male Syrian hamsters were divided into four groups: atherogenic animals (AT) induced by standard diet supplemented with 3% cholesterol and 15% butter; AT animals treated with Nifedipine (20 or 60 mg/kg/day); AT hamsters treated with Diltiazem (45 mg/kg/day) and controls (C), fed a standard chow diet. For one month, the drugs were administered concomitantly with the atherogenic diet. During the experiment, serum cholesterol, free calcium and angiotensin-converting enzyme (ACE) activity values were determined. Specimens from the lesion-prone areas: aortic valves, coronary arteries, and aortic arch, were collected and processed for light and electron microscopy. The results show that the atherogenic diet induces a significant increase of serum cholesterol (389 +/- 67.47 mg/dl), free calcium (13.44 +/- 0.84 mg/dl) and ACE activity (78.46 +/- 9.25 mU/ml) as compared to controls (cholesterol 73.76 +/- 3.31 mg/dl; calcium 8.9 +/- 0.5 mg/dl; ACE 33.68 +/- 2.6 mU/ml). Administration of Diltiazem reduced significantly these parameters (cholesterol, 196.25 +/- 22 mg/dl; calcium, 8.41 +/- 0.6 mg/dl) while Nifedipine had no effect (cholesterol, 283.03 +/- 44.7 mg/dl; calcium, 11.13 +/- 1.25 mg/dl) and increased the ACE activity (100.28 +/- 36.9 mU/ml). At the structural level, a significant correlation between the apparition and progression of the atherosclerotic lesions and the biochemical parameters detected, was observed. Diltiazem treated animals showed a reduction in the lesion severity, at the level of aortic valves, coronary arteries and aortic arch; we assume that Diltiazem acts on the early phases of atherosclerosis by blocking the lipid transport and accumulation into the subendothelial space. In contradistinction, Nifedipine treatment failed to suppress the atherogenic effect of fat-rich diet, and as in AT hamsters, the plaques developed in all lesion-prone areas. The latter were characterised by numerous lipid-laden cells (in aorta and aortic valves) and calcification and necrotic centres, in all locations, including coronary arteries. The results suggest a different mechanism of action and the ensuing effects of various CCB on atherogenesis.
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PMID:Differential effect of two calcium channel blockers--nifedipine and diltiazem--on atherogenesis in hypercholesterolemic hamster. 896 51


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