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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Framingham Study established hypertension as a major cardiovascular risk factor and quantified its atherogenic cardiovascular disease potential. An historical perspective is presented on the epidemiological insights about hypertension derived from 50 years of Framingham Study research into the prevalence, incidence, determinants and hazards of hypertension. Existing misconceptions about the presence of critical levels of blood pressure, the impact of the systolic and diastolic components of blood pressure, the hazard 'mild' hypertension, the impact in advanced age and the hazard of left ventricular hypertrophy. The importance of isolated systolic hypertension and the pulse pressure were demonstrated. It has been demonstrated that hypertension seldom occurs in isolation of other atherogenic risk factors, with which it tends to cluster. This clustering with other metabolically linked risk factors has been shown to reflect insulin resistance promoted by weight gain and abdominal obesity. Obesity was shown to be one of the major determinants of hypertension in the general population. Left ventricular hypertrophy was shown to be an ominous harbinger of cardiovascular disease rather than an incidental compensatory phenomenon. Multivariate risk profiles for coronary disease, stroke, peripheral artery disease and heart failure have been devised to facilitate incorporation of elevated blood pressure in a global, multivariate cardiovascular risk assessment.
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PMID:Fifty years of Framingham Study contributions to understanding hypertension. 1072 12

The Heart Outcomes Prevention Evaluation (HOPE) study found that the ACE inhibitor ramipril can lower the risk of atherosclerotic disease events and death in patients without heart failure but with known atherosclerosis or with diabetes plus at least one cardiovascular risk factor. This benefit was independent of ramipril's effect on blood pressure. Additional benefits were a reduced risk of diabetic nephropathy in diabetic patients, and a lower likelihood of newly diagnosed diabetes. On the other hand, vitamin E in the doses and duration studied (400 IU/day for 4.5 years) did not lower risk significantly.
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PMID:The HOPE study. Ramipril lowered cardiovascular risk, but vitamin E did not. 1078 Jan 1

Experimental and epidemiological evidence suggests that activation of the reninangiotensin-aldosterone system and oxidative modification of low density lipoprotein cholesterol both play important roles in atherosclerosis. A substudy of the HOPE (Heart Outcomes Prevention Evaluation) trial, the SECURE trial (Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E), evaluated the effects of long-term treatment with the angiotensin-converting enzyme (ACE) inhibitor, ramipril, and with vitamin E on atherosclerosis progression in high risk patients. A total of 732 patients were enrolled into the study. These patients were 55 years or older, had vascular disease or diabetes with at least one other cardiovascular risk factor, but did not have heart failure or low ejection fraction. Patients were randomly assigned according to a three-by-two factorial design to receive placebo, ramipril 2.5 mg/day or ramipril 10 mg/day and placebo or vitamin E 400 IU/day. Progression of atherosclerosis was evaluated by B-mode carotid ultrasonography. The primary outcome evaluated was the annualised progression slope of the mean maximum carotid intimal-medial thickness (IMT) across 12 pre-selected carotid arterial segments. The average follow-up was 4.5 years. The progression slope of the mean maximum IMT was 0.0217 +/- 0.04 mm/year in the placebo group, 0.018 +/- 0.44 mm/year in the ramipril 2.5 mg/day group and 0.0137 +/- 0.04 in the ramipril 10 mg/day group (P = 0.33 for the overall effect of ramipril and P = 0.028 for the comparison between patients receiving ramipril placebo and ramipril 10 mg/day). The reduction in atherosclerotic progression observed with ramipril remained significant after adjusting for systolic and diastolic blood pressure changes (P = 0.043) and after multivariate adjustment (P = 0.046). Administration of vitamin E 400 IU/day had no impact on atherosclerosis progression. The SECURE study is the first demonstration, in human subjects, of an effect of ACE inhibition on atherosclerotic progression. This benefit cannot be explained by the lowering of blood pressure alone. Vitamin E 400 IU/day had a neutral effect on the ultrasound measurements of atherosclerosis progression in the SECURE trial.
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PMID:Modifying the natural history of atherosclerosis: the SECURE trial. 1171 53

There is a paucity of high quality studies on the prognostic importance of arterial pressure in end-stage renal disease. Furthermore, the optimal timing for blood pressure (BP) measurements (pre- or postdialysis), and the prognostic value of 24-hour ambulatory BP monitoring in these patients remain to be established. In end-stage renal disease patients without diabetes and heart failure, predialysis systolic, diastolic, and pulse pressure are strongly and independently related to left ventricular mass, and the strength of these relationships is higher than that between the corresponding postdialysis values and left ventricular mass. Average predialysis systolic pressure (monthly average) is associated with left ventricular mass as strongly as 24-hour systolic BP, which suggests that the average routine predialysis BP taken over 1 month may be equally representative of the "true" BP (the integrated BP load) than 24-hour ambulatory BP monitoring. Mortality is U shaped in large hemodialysis databases. In the only prospective study that adequately controlled for cardiac function at baseline, it was shown that hypertension is associated with a higher risk of developing congestive heart failure, and that patients with left ventricular hypertrophy or chronic heart failure are at a much higher risk of mortality than patients without these complications. The role of arterial stiffening (pulse pressure) as a cardiovascular risk factor has been firmly established in an analysis of a very large dialysis database in the United States, and by recent studies based on direct measurements of pulse wave velocity.
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PMID:Hypertension as a cardiovascular risk factor in end-stage renal failure. 1221 57

In people with diabetes, renal disease tends to progress from microalbuminuria to clinical proteinuria to renal insufficiency. Little evidence has been published for the nondiabetic population. This study retrospectively analyzed changes of proteinuria over 4.5 yr in the HOPE (Heart Outcomes and Prevention Evaluation) study, which compared ramipril's effects to placebo in 9297 participants, including 3577 with diabetes and 1956 with microalbuminuria. This report is restricted to 7674 participants with albuminuria data at baseline and at follow-up. Inclusion criteria were known vascular disease or diabetes plus one other cardiovascular risk factor, exclusion criteria included heart failure or known impaired left ventricular function, dipstick-positive proteinuria (>1+), and serum creatinine >2.3 mg/dl (200 microM). Baseline microalbuminuria predicted subsequent clinical proteinuria for the study participants overall (adjusted odds ratio [OR], 17.5; 95% confidence interval [CI], 12.6 to 24.4), in participants without diabetes (OR, 16.7; 95% CI, 8.6 to 32.4), and in participants with diabetes (OR, 18.2; 95% CI, 12.4 to 26.7). Any progression of albuminuria (defined as new microalbuminuria or new clinical proteinuria) occurred in 1859 participants; 1542 developed new microalbuminuria, and 317 participants developed clinical proteinuria. Ramipril reduced the risk for any progression (OR, 0.87; 95% CI, 0.78 to 0.97; P = 0.0146). People without and with diabetes who are at high risk for cardiovascular disease are also at risk for a progressive rise in albuminuria. Microalbuminuria itself predicts clinical proteinuria in nondiabetic and in diabetic people. Ramipril prevents or delays the progression of albuminuria.
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PMID:Development of renal disease in people at high cardiovascular risk: results of the HOPE randomized study. 1259 99

To investigate the impact of treatment on cardiovascular mortality and morbidity, we assessed outcomes in patients with hypertension and diabetes who received co-amilozide or nifedipine in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension. Participants had to be 55 to 80 years of age, with hypertension (> or =150/95 or > or =160 mm Hg) and at least one additional cardiovascular risk factor. Patients received 30 mg nifedipine once daily or co-amilozide (25 mg hydrochlorothiazide and 2.5 mg amiloride) daily. Doses were doubled if target blood pressures (<140/90 mm Hg) were not achieved. Primary (composite of cardiovascular death, myocardial infarction, heart failure, and stroke) and secondary outcomes (composite of primary outcomes, including all-cause mortality and death from vascular and nonvascular causes) were assessed by means of intent-to-treat analyses. There was no significant difference in the incidence of primary outcomes between nifedipine-treated and co-amilozide-treated patients with diabetes at baseline (n=1302) (8.3% versus 8.4%; relative risk, 0.99, 95% CI, 0.69 to 1.42; P=1.00). A significant benefit for nifedipine-treated patients was seen for the composite secondary outcome (14.2% versus 18.7%; relative risk, 0.76, 95% CI, 0.59 to 0.97; P=0.03). Among patients without diabetes at baseline (n=5019), there was a significant difference in the incidence of new diabetes (nifedipine 4.3% versus co-amilozide 5.6%, P=0.023). Nifedipine GITS once daily is as effective as diuretic therapy in reducing cardiovascular complications in hypertensive diabetics. Nifedipine-treated patients were also less likely to have diabetes or have secondary events (a composite of all-cause mortality, death from a vascular cause, and death from a nonvascular cause) than co-amilozide recipients. Our results suggest that nifedipine could be considered as first-line therapy for hypertensive diabetics.
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PMID:Outcomes with nifedipine GITS or Co-amilozide in hypertensive diabetics and nondiabetics in Intervention as a Goal in Hypertension (INSIGHT). 1292 58

Ramipril is safe and effective in the treatment of hypertension and heart failure, but this is not reviewed here. Ramipril is a lipophilic angiotensin-converting enzyme inhibitor suitable for once-daily administration. In addition to decreasing angiotensin II and increasing bradykinin levels, ramipril increases the levels of vasodilatory renal medullary neutral lipids and inhibits platelet-derived growth factor-induced proliferation of glomerulus cells. Ramipril also decreases transforming growth factor-beta in the kidney. Changes in kidney structure and proteinuria are characteristics of the streptozotocin (STZ) rat model of diabetes, and these are prevented by ramipril. In STZ diabetes, doses of ramipril that have no effect on blood pressure reverse vascular hypertrophy. In animal models of kidney failure (subtotal nephrectomy, stroke-prone spontaneously hypertensive rats), ramipril is renoprotective and some of this renoprotective effect is independent of blood pressure lowering. In humans, clinical doses of ramipril probably do not modify glucose metabolism but do reduce the levels of LDL- and HDL-cholesterol. In clinical trials of renal effects, ramipril has been shown to increase cortical nephron flow in hypertension and to reduce proteinuria in patients with and without diabetes and/or hypertension. Some of the smaller clinical trials showed beneficial effects on kidney function with low doses of ramipril that do not lower blood pressure. A large clinical trial in nondiabetic proteinuria, the Ramipril Efficacy in Nephropathy (REIN) trial, has shown that ramipril 1.25 mg/day, which does not lower blood pressure, arrested the decline in glomerular filtration rate and prolonged the time to end-stage renal failure. In diabetic patients who have had a previous cardiovascular event or having one other cardiovascular risk factor, the MICRO-HOPE clinical trial showed that ramipril lowers the combined risk of myocardial infarction, stroke and cardiovascular death by 25%. In conclusion, ramipril has proven beneficial effects in kidney disease alone or in association with diabetes and in diabetes without kidney disease, and is the pril for diabetes and kidney disease. (c) 2001 Prous Science. All rights reserved.
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PMID:Is Ramipril the pril for diabetes and kidney disease? 1276 20

There is abundant evidence that the endothelium plays a crucial role in the maintenance of vascular tone and structure. One of the major endothelium-derived vasoactive mediators is nitric oxide (NO), which has been characterized as an "endogenous anti-atherosclerotic molecule". Synthesis of NO can be selectively inhibited by guanidino-substituted analogs of L-arginine, which act as competitive inhibitors at the active site of the enzyme. One such analog is asymmetric dimethylarginine (ADMA), a compound that has been found in human plasma and urine and exerts the activity of an endogenous inhibitor of NO synthase. In contrast to ADMA, its regioisomer symmetric dimethylarginine (SDMA) does not inhibit NO synthase. The methyl groups contained within the dimethylarginine molecules are derived from S-adenosylmethionine, an intermediate in the homocysteine/methionine pathway. There is experimental evidence that homocysteine may affect endothelium-dependent vascular function by increasing the formation of ADMA. Both ADMA and SDMA are eliminated from the body by renal excretion. In addition, the metabolism of ADMA, but not SDMA, occurs via hydrolytic degradation to citrulline and dimethylamine by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). Data from experimental studies suggest that ADMA inhibits vascular NO elaboration at concentrations found in pathophysiological conditions (i.e., 3-15 microM). ADMA likely acts as an autocrine regulator of endothelial NO synthase activity. When rabbits are placed on a diet enriched with 1% cholesterol, ADMA levels are increased within 4 weeks of dietary intervention as compared to control animals. Elevated plasma concentrations of ADMA are also present in hypercholesterolemic and hypertensive patients, in patients with chronic heart failure, and in other patient groups at high risk of developing cardiovascular disease. Elevation of ADMA induces dysfunction of the endothelium, which becomes clinically evident by impaired endothelium-dependent vasodilation, hyperaggregability of platelets, and enhanced monocyte adhesion. Recent prospective studies suggest that endothelial dysfunction indicates an increased risk of future cardiovascular events. In line with these observations, we and others found evidence that ADMA is a novel cardiovascular risk factor.
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PMID:Association of asymmetric dimethylarginine and endothelial dysfunction. 1465 27

There is abundant evidence now that the endothelium plays a crucial role in the maintenance of vascular tone and structure. One of the major endothelium-derived vasoactive mediators is nitric oxide (NO). Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase. ADMA inhibits vascular NO production at concentrations found in pathophysiological conditions; ADMA also causes local vasoconstriction when it is infused intra-arterially. ADMA is increased in plasma of humans with hypercholesterolemia, atherosclerosis, hypertension, chronic renal failure, and chronic heart failure. Increased ADMA levels are associated with reduced NO synthesis as assessed by impaired endothelium-dependent vasodilation. In several prospective and cross-sectional studies, ADMA evolved as a marker of cardiovascular risk in certain populations like hemodialysis patients, non-smoking men, or intensive-care patients. The CARDIAC study is a multicenter case-control study designed to address the hypothesis that ADMA may be a suitable and sensitive marker of cardiovascular risk in a large, unselected population of both sexes, and with a broad range of established cardiovascular risk factors. The population included in the CARDIAC study will be prospectively followed for a scheduled follow-up period of 4 years, and the data of the CARDIAC-PRO study will then provide definite evidence whether ADMA may be prospectively determined as a cardiovascular risk factor.
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PMID:Plasma concentration of asymmetric dimethylarginine and the risk of coronary heart disease: rationale and design of the multicenter CARDIAC study. 1466

Nonepithelial effect of aldosterone has been recognized as a cardiovascular risk factor independent of elevation of blood pressure. Pro-inflammatory effect of aldosterone in vasculature appears to be an initiating event for the target organ injuries. Recent clinical trials of aldosterone receptor blockers in congestive heart failure indicate the efficacy of aldosterone antagonism to prevent cardiac death. In addition to elevated plasma levels of aldosterone, mineralocorticoid receptor expression in cardiovascular tissues may contribute to the progression of heart failure. In this review, emerging role of aldosterone as a cardiovascular risk is highlighted.
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PMID:[Aldosterone]. 1473 33


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