ISSN:0194-911X    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Abstract—There is increasing evidence that direct pathobiological events in the vessel wall play an important role in vascular disease. An important mechanism involves the perturbation of the homeostatic balance between NO and reactive oxygen species. Increased reactive oxygen species can inactivate NO and produce peroxynitrite. Angiotensin II is a potent mediator of oxidative stress and stimulates the release of cytokines and the expression of leukocyte adhesion molecules that mediate vessel wall inflammation. Inflammatory cells release enzymes (including ACE) that generate angiotensin II. Thus, a local positive-feedback mechanism could be established in the vessel wall for oxidative stress, inflammation, and endothelial dysfunction. Angiotensin II also acts as a direct growth factor for vascular smooth muscle cells and can stimulate the local production of metalloproteinases and plasminogen activator inhibitor. Taken together, angiotensin II can promote vasoconstriction, inflammation, thrombosis, and vascular remodeling. In this article, we propose a model that unifies the interrelationship among cardiovascular risk factors, angiotensin II, and the pathobiological mechanisms contributing to cardiovascular disease. This model may also explain the beneficial effects of ACE inhibitors on cardiovascular events beyond blood pressure reduction.

ISSN:0194-911X    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Abstract—Cardiovascular diseases (CVDs) are the major causes of mortality in persons with diabetes, and many factors, including hypertension, contribute to this high prevalence of CVD. Hypertension is approximately twice as frequent in patients with diabetes compared with patients without the disease. Conversely, recent data suggest that hypertensive persons are more predisposed to the development of diabetes than are normotensive persons. Furthermore, up to 75% of CVD in diabetes may be attributable to hypertension, leading to recommendations for more aggressive treatment (ie, reducing blood pressure to <130/85 mm Hg) in persons with coexistent diabetes and hypertension. Other important risk factors for CVD in these patients include the following: obesity, atherosclerosis, dyslipidemia, microalbuminuria, endothelial dysfunction, platelet hyperaggregability, coagulation abnormalities, and “diabetic cardiomyopathy.” The cardiomyopathy associated with diabetes is a unique myopathic state that appears to be independent of macrovascular/microvascular disease and contributes significantly to CVD morbidity and mortality in diabetic patients, especially those with coexistent hypertension. This update reviews the current knowledge regarding these risk factors and their treatment, with special emphasis on the cardiometabolic syndrome, hypertension, microalbuminuria, and diabetic cardiomyopathy. This update also examines the role of the renin-angiotensin system in the increased risk for CVD in diabetic patients and the impact of interrupting this system on the development of clinical diabetes as well as CVD.

ISSN:0194-911X    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

In exploration of the association between pulse pressure and longevity in humans, 3 hypotheses are briefly discussed: the fetal origin hypothesis, antagonistic pleiotropy, and the telomere hypothesis of cellular aging. The implications of these hypotheses serve to draw a critical distinction between biologic age (aging) and chronological age and, thereby, offer an answer to a question that presently matters most in the field of hypertension: Why has it been so difficult to disentangle the genetic components of essential hypertension and to identify the variant genes responsible for elevated blood pressure in a large segment of the human population?

ISSN:0194-911X    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

We examined the relation of serum creatinine and uric acid to mortality and cardiovascular disease in older (aged ≥60 years) Chinese patients with isolated systolic hypertension (systolic/diastolic blood pressure ≥160/<95 mmHg). We used Cox regression to correlate outcome with baseline serum creatinine and uric acid measured in 1880 and 1873, respectively, of the 2394 patients enrolled in the placebo-controlled Systolic Hypertension in China (Syst-China) Trial. Median follow-up was 3 years. In multiple Cox regression analysis with adjustment for gender, age, active treatment, and other significant covariates, serum creatinine was significantly associated with a worse prognosis. The relative hazard rates (95% CIs) associated with a 20-&mgr;mol/L increase in serum creatinine for all-cause, cardiovascular, and stroke mortality were 1.16 (1.05 to 1.27,P=0.003), 1.15 (1.01 to 1.31,P=0.03), and 1.37 (1.13 to 1.65,P=0.001), respectively. In a similar analysis, which also accounted for serum creatinine, serum uric acid was also significantly and independently associated with excess mortality of cardiovascular disease and stroke. The relative hazard rates associated with a 50-&mgr;mol/L increase of serum uric acid were 1.14 (1.02 to 1.27,P=0.02) for cardiovascular mortality and 1.34 (1.14 to 1.57,P<0.001) for fatal stroke. In conclusion, in older Chinese patients with isolated systolic hypertension, serum creatinine and serum uric acid were predictors of mortality.

ISSN:0194-911X    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Large-vessel manifestations of systemic lupus erythematosus (SLE), a multisystem disease characterized by disturbances in the immune system, include higher than expected rates of hypertension and cardiovascular disease. Reductions in the elasticity of central arteries may act as a marker of early changes that predispose to the development of major vascular disease. This study evaluated risk factors associated with aortic stiffness measured by pulse wave velocity (PWV) in women with SLE. We expected SLE-specific factors, especially variables indicative of inflammation and active disease, to be associated with increasing PWV. The study population included 220 women currently enrolled in the Pittsburgh Lupus Registry. All risk factor data were collected on the day of the ultrasound examinations. PWV waveforms were collected from the right carotid and femoral arteries by Doppler probes. The mean age of the women was 45.5±10.8 years, the median SLE disease duration approximated 9 years, and the mean PWV was 6.1±1.7 m/s. Multiple regression models were stratified by menopausal status. Among postmenopausal women, PWV risk factors were primarily traditional factors and included age, systolic blood pressure, family history of vascular disease, carotid plaque, creatinine, obesity, glucose, white cell count, and cumulative SLE organ damage. Among premenopausal women, PWV risk factors consisted of a mix of SLE-related and traditional variables and included higher C3 levels, presence of ds-DNA antibodies, nonuse of hydroxychloroquine, lower leukocyte count, higher mean arterial pressure, and carotid plaque. SLE-specific variables appeared to be associated with increases in aortic PWV, indicating central artery stiffening. This was seen most clearly among premenopausal women. This finding may partially explain the higher rates of cardiovascular disease and hypertension observed in young women with SLE.

ISSN:0194-911X    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Abstract—In hypertension, both reduced vascular supply and increased cardiac demand contribute to the development of (silent) myocardial ischemia. Our aim was to determine the prevalence of ST-segment depression and to analyze contributing factors in asymptomatic, previously untreated, older hypertensives. From a population survey, in 184 patients with mild hypertension (4 times systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥95 mmHg), 60 to 75 years of age, cardiovascular end-organ damage was measured. Episodes of ST-segment depression were measured by 48-hour ambulatory Holter monitoring and were observed in 21 hypertensives (12%). They showed a significantly higher combined far-wall intima-media thickness of carotid and femoral arteries and more arterial plaques as measured by B-mode ultrasound compared with hypertensives without ST depression (0.00098±0.00021 versus 0.00088±0.00016 mm and 5.2±3.7 versus 3.7±2.8 plaques,P<0.05, respectively), whereas left ventricular mass index was not different (111±18 versus 104±24 g/m2;P=0.18, respectively). In hypertensives with transient ST-segment depression, a significant relation was found between left ventricular mass and ischemic burden (r=0.51,P=0.02). Approximately 1 of 8 unselected and previously untreated older hypertensives show asymptomatic ST-segment depression, suggestive of silent myocardial ischemia. These data suggest that vascular factors mainly determine the occurrence of ischemic ST-segment depression and cardiac factors determine the ischemic burden in older hypertensives.

ISSN:0194-911X    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Abstract—Dendroaspis natriuretic peptide (DNP), a recently discovered peptide, shares structural similarity to the other known natriuretic peptides, ANP, BNP, and CNP. Studies have reported that DNP is present in human and canine plasma and atrial myocardium and increased in plasma of humans with congestive heart failure (CHF). In addition, synthetic DNP is markedly natriuretic and diuretic and is a potent activator of cGMP in normal animals. To date, the ability of synthetic DNP to improve cardiorenal function in experimental CHF is unknown. Synthetic DNP was administered intravenously at 10 and 50 ng · kg−1· min−1in dogs (n=7) with severe CHF induced by rapid ventricular pacing for 10 days at 245 bpm. In addition, we determined endogenous DNP in normal (n=4) and failing (n=4) canine atrial and ventricular myocardium. We report that administration of synthetic DNP in experimental severe CHF has beneficial cardiovascular, renal, and humoral properties. First, DNP in CHF decreased cardiac filling pressures, specifically right atrial pressure and pulmonary capillary wedge pressure. Second, DNP increased glomerular filtration rate in association with natriuresis and diuresis despite a reduction in mean arterial pressure. Third, DNP increased plasma and urinary cGMP and suppressed plasma renin activity. Fourth and finally, we report that DNP immunoreactivity is present in canine atrial and ventricular myocardium and increased in CHF. These studies report the acute intravenous actions of synthetic DNP in experimental severe CHF and suggest that on the basis of its beneficial properties, DNP may have potential as a new intravenous agent for the treatment of decompensated CHF.

ISSN:0194-911X    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Our previous studies show that cardiac fibroblasts express the extracellular “cAMP-adenosine pathway,” that is, the generation of adenosine from extracelluar cAMP. The goal of this study was to assess whether activation of the cAMP-adenosine pathway by stimulation of endogenous cAMP synthesis regulates cardiac fibroblast growth. Cardiac fibroblasts in 3D cultures were used as the model system. Treatment of cardiac fibroblasts with forskolin, isoproterenol, or norepinephrine increased cAMP production and extracellular levels of adenosine, and these effects were prevented by inhibition of adenylyl cyclase (2′,5′-dideoxyadenosine). Treatment with forskolin, isoproterenol, or norepinephrine for 24 hours inhibited DNA synthesis (3H-thymidine incorporation), and this effect was enhanced by combined inhibition of adenosine deaminase (erythro-9-[2-hydroxy-3-nonyl] adenine) plus adenosine kinase (iodotubercidin). Inhibition of adenylyl cyclase or adenosine receptors (1,3-dipropyl-8-p-sulfophenylxanthine or KF17837) prevented the effects of forskolin, isoproterenol, and norepinephrine on DNA synthesis. Forskolin also inhibited protein synthesis (3H-leucine incorporation) and cell proliferation, and these effects were blocked by adenosine receptor antagonism. Treatment of cardiac fibroblasts with norepinephrine for >48 hours but not <48 hours increased DNA synthesis, protein synthesis, and cell number. However, blockade of adenylyl cyclase or antagonism of adenosine receptors caused norepinephrine to induce proliferation in <48 hours. Our findings indicate that the endogenous cAMP-adenosine pathway regulates cardiac fibroblast growth.

ISSN:0194-911X    

出版商:OVID    

年代:2001

数据来源: OVID