Microalbuminuria: marker of vascular dysfunction,risk factor for cardiovascular disease

Based on the data from large single and multi-center clinical trials, including the Heart Outcomes Prevention Evaluation (HOPE) study, it is clear that the presence of microalbuminuria is a signal from the kidney that cardiovascular risk is increased and that vascular responses are altered. This is exemplified by studies that have demonstrated that the compensatory vasodilation seen following relief from prolonged ischemia or infusion of vasodilators such as nitroglycerin is blunted in people with microalbuminuria. Thus, the presence of between 30 and 299 mg/day of albumin in the urine is associated with abnormal vascular responsiveness, which may be the result of more advanced atherosclerosis and not necessarily related to the presence of hypertension or renal disease. Agents known to reduce the rise in microalbuminuria or actually reduce the level of microalbuminuria, such as ACE inhibitors, angiotensin receptor blockers, HMG-CoA reductase inhibitors, beta blockers, non-dihydropyridine calcium channel blockers and diuretics, have all been shown to reduce cardiovascular mortality and in some cases preserve renal function. This article will present an overview of the data that support the assertion that a reduction in the rise of microalbuminuria is a significant consideration in the selection of agents to treat a given risk factor (cholesterol or blood pressure) to a recommended target goal. Achieving such a goal with agents that also impact microalbuminuria will provide for a more complete cardiovascular risk reduction.     

Risk factors for cardiovascular disease and endothelin-1 levels in Takayasu arteritis patients

The objective of this study was to evaluate traditional risk factors for cardiovascular disease (CVD) and endothelin-1 (ET-1) levels in Takayasu arteritis (TA) patients. Twenty-two TA patients and 37 controls were evaluated. TA patients had a higher prevalence of hypertension (63.6% vs. 21.6%, p = 0.001) and higher levels of triglycerides (129.5 mg/dL ± 70.8 vs. 88.4 mg/dL ± 60.8, p = 0.017) than controls. Mean number of CVD risk factors was 1.64 ± 1.22 in TA patients and 1.03 ± 1.44 among controls, p = 0.030. More TA patients presented at least one CVD risk factor when compared to controls (77.2% vs. 51.3%, p = 0.048). ET-1 levels were higher in patients than in controls (1.49 pg/mL ± 0.45 vs. 1.27 pg/mL ± 0.32, p = 0.034), however no significant difference was found between patients with active and inactive disease. In this study, TA patients presented a higher prevalence of hypertension, higher levels of triglycerides, and ET-1 than controls.     

Feto-placental vascular dysfunction as a prenatal determinant of adult cardiovascular disease

The objective of the study is to assess the effects of emphysema on peak oxygen uptake ( $ \dot{V}{\text{O}}_{{ 2 {\text{peak}}}} $ ) during a cardiopulmonary exercise test in patients with chronic obstructive pulmonary disease (COPD). We measured $ \dot{V}{\text{O}}_{{ 2 {\text{peak}}}} $ and oxygen pulse in 80 patients with stable COPD exercising maximally. Oxygen saturation was measured by pulse oximetry (SpO₂), and the ventilatory response assessed by the ratio of tidal volume (V _T) at peak to slow vital capacity (SVC) at baseline, and by the percent increase of peak V _T over baseline. Computed tomography imaging (CT scan) served as the reference diagnostic standard for emphysema. Based on the panel-grading (PG) method, emphysema was rated absent or mild (PG ≤ 30, n = 54), or moderate to severe (PG > 30, n = 26). Multiple quantile regression was applied to estimate the effects of PG > 30 on $ \dot{V}{\text{O}}_{{ 2 {\text{peak}}}} $ . At peak exercise, the patients with PG > 30 had significantly lower $ \dot{V}{\text{O}}_{ 2} $ , oxygen pulse and SpO₂, and featured a blunted ventilatory response with respect to those with PG ≤ 30 (p < 0.001). With multiple quantile regression, the effects of PG > 30 on $ \dot{V}{\text{O}}_{{ 2 {\text{Peak}}}} $ were only partially explained by the degree of lung hyperinflation, a substantial component being imputable to impairment of lung diffusing capacity. In conclusion, chronic obstructive pulmonary disease patients with moderate to severe emphysema feature significantly lower exercise tolerance than those with no or mild emphysema. Our findings underscore the need of tailoring therapeutic interventions for COPD to the predominant clinical phenotype to improve exercise capacity.     

The prevalence of erectile dysfunction in the primary care setting: importance of risk factors for diabetes and vascular disease

BACKGROUND: The prevalence of erectile dysfunction (ED) and associated risk factors has been described in many clinical settings, but there is little information regarding men seen by primary care physicians. We sought to identify independent factors associated with ED in a primary care setting. METHODS: We surveyed a cross-sectional sample of 3921 Canadian men, aged 40 to 88 years, seen by primary care physicians. Participants completed a full medical history, physical examination, and measurement of fasting blood glucose and lipid levels. We used the International Index of Erectile Function to define ED as a score of less than 26 on the erectile function domain. RESULTS: The overall prevalence of ED was 49.4%. The presence of cardiovascular disease (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.16-1.81; P<.01) or diabetes (OR, 3.13; 95% CI, 2.35-4.16; P<.001) increased the probability of ED after adjustment for other confounders. Among those individuals without cardiovascular disease or diabetes, the calculated 10-year Framingham coronary risk (OR, 1.03 per 1% increase; 95% CI, 1.02-1.05; P<.001) and fasting blood glucose levels (OR, 1.14 per 18-mg/dL [1-mmol/L] increase; 95% CI, 1.04-1.24; P<.01) were independently associated with ED. Erectile dysfunction was also independently associated with undiagnosed hyperglycemia (OR, 1.46; 95% CI, 1.02-2.10; P = .04), impaired fasting glucose (OR, 1.26; 95% CI, 1.08-1.46; P = .004), and the metabolic syndrome (OR, 1.45; 95% CI, 1.24-1.69; P<.001). CONCLUSIONS: Cardiovascular disease, diabetes, future coronary risk, and increasing fasting glucose levels are independently associated with ED. It remains to be determined if ED precedes the development of these conditions.     

The relative importance of vascular structure and function in predicting cardiovascular events

OBJECTIVES: We sought to assess the prognostic utility of brachial artery reactivity (BAR) in patients at risk of cardiovascular events. BACKGROUND: Impaired flow-mediated vasodilation measured by BAR is a marker of endothelial dysfunction. Brachial artery reactivity is influenced by risk factors and is responsive to various pharmacological and other treatments. However, its prognostic importance is uncertain, especially relative to other predictors of outcome. METHODS: A total of 444 patients were prospectively enrolled to undergo BAR and follow-up. These patients were at risk of cardiovascular events, based on the presence of risk factors or known or suspected cardiovascular disease. We took a full clinical history, performed BAR, and obtained carotid intima-media thickness (IMT) and left ventricular mass and ejection fraction. Patients were followed up for cardiovascular events and all-cause mortality. Multivariate Cox regression analysis was performed to assess the independent association of investigation variables on outcomes. RESULTS: The patients exhibited abnormal BAR (5.2 +/- 6.1% [mean +/- SD]) but showed normal nitrate-mediated dilation (9.9 +/- 7.2%) and normal mean IMT (0.67 +/- 0.12 mm [average]). Forty-nine deaths occurred over the median follow-up period of 24 months (interquartile range 10 to 34). Patients in the lowest tertile group of BAR (<2%) had significantly more events than those in the combined group of highest and mid-tertiles (p = 0.029, log-rank test). However, mean IMT (rather than flow-mediated dilation) was the vascular factor independently associated with mortality, even in the subgroup (n = 271) with no coronary artery disease and low risk. CONCLUSIONS: Brachial artery reactivity is lower in patients with events, but is not an independent predictor of cardiovascular outcomes in this cohort of patients.     

The importance of the monoamine oxidase inhibitors in cardiovascular disease

Because of their antianginal and antidepressive actions, monoamine oxidase inhibitors provide appreciable benefit in 70 per cent of patients with cardiovascular disease. Increase in exercise tolerance is the most noteworthy effect. If treatment is individualized, side effects are few and easily counteracted.     

Erectile dysfunction: a disease marker for cardiovascular disease

Previous studies have shown an increased incidence of erectile dysfunction (ED) among patients diagnosed with cardiovascular disease (CVD). Both conditions, which may be a consequence of underlying endothelial dysfunction, share many risk factors such as hypertension, dyslipidemia, diabetes, depression, obesity, and cigarette smoking. Because vascular disturbance of the penile endothelium leads to ED, the possibility arises that ED may be an early indicator for systemic endothelial dysfunction and subsequent CVD. Recognizing ED as a disease marker for CVD may help to identify individuals at risk for having a premature cardiovascular event.     

Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease

OBJECTIVES: The goal of this study was to prospectively examine the long-term predictive value of brachial-artery endothelial dysfunction for future cardiovascular events. BACKGROUND: Brachial-artery endothelial function is impaired in individuals with atherosclerosis and coronary risk factors. The prospective relation between endothelial function determined by brachial-artery ultrasound and long-term cardiovascular risk is unknown. METHODS: We examined brachial-artery endothelial function using ultrasound in 199 patients with peripheral arterial disease before elective vascular surgery. Patients were prospectively followed with an average follow-up of 1.2 years after surgery. RESULTS: Thirty-five patients had an event during follow-up, including cardiac death (5 patients), myocardial infarction (17 patients), unstable angina (10 patients), or stroke (3 patients). Preoperative endothelium-dependent flow-mediated dilation (FMD) was significantly lower in patients with an event (4.4 +/- 2.8%) compared with those without an event (7.0 +/- 4.9%, p < 0.001), whereas endothelium-independent vasodilation to nitroglycerin was similar in both groups. In a Cox proportional-hazards model, independent predictors of events included age (p = 0.003), more invasive surgery (surgery other than carotid endarterectomy, p = 0.02), and impaired brachial-artery endothelial function (p = 0.002). Risk was approximately nine-fold higher in patients with FMD <8.1% (lower two tertiles) compared with those in the upper tertile (odds ratio 9.5; 95% confidence interval 2.3 to 40). CONCLUSIONS: Impaired brachial-artery endothelial function independently predicts long-term cardiovascular events in patients with peripheral arterial disease. The findings suggest that noninvasive assessment of endothelial function using brachial-artery FMD may serve as a surrogate end point for cardiovascular risk.     

Diabetes is a vascular disease: the role of endothelial dysfunction in pathophysiology of cardiovascular disease in diabetes

Diabetes is a vascular disease. Endothelial dysfunction is the initial process in vascular manifestations of diabetes mellitus (DM). There are multiple pathways involved in the pathophysiologic process related to endothelial dysfunction in DM. Most of these abnormalities occur secondary to insulin resistance. In this article the role of insulin, glucose,dyslipidemia, oxidative stress and various cellular mechanisms related to endothelial dys-function in diabetes are discussed in detail.     

勃起功能障碍与心血管疾病

近来发现 ,勃起功能障碍与心血管疾病关系密切。在发病机制上 ,二者呈鲜明的共因和互为因果关系 ;在治疗上 ,二者之间的相互影响十分显著     

Vitamin C blocks vascular dysfunction and release of interleukin-6 induced by endothelin-1 in humans in vivo

OBJECTIVE: Inflammation of the vessel wall is of importance in atherosclerosis. Endothelin-1 (ET-1) exerts pro-inflammatory effects and contributes to endothelial dysfunction. The objective was to test whether ET-1 impairs vascular function by increasing oxidative stress and release of pro-inflammatory cytokines in humans. METHODS: Forearm blood flow (FBF) was determined in 12 young healthy males with venous occlusion plethysmography. RESULTS: Intra-brachial infusion of ET-1 (20 pmol/min) decreased both endothelium-dependent and -independent vasodilatation (P<0.001). ET-1 also increased venous IL-6 levels (0.96+/-0.14-1.40+/-0.15 ng/ml; P<0.001). Administration of Vitamin C (24 mg/min) following the ET-1 infusion did not restore vascular function. However, pre-treatment with Vitamin C before ET-1 prevented the decrease in endothelium-dependent and -independent vasodilatation as well as the increase in IL-6 levels (1.20+/-0.28 versus 1.29+/-0.27 ng/ml; P=0.57). Infusion of a control vasoconstrictor substance, noradrenaline (80 ng/min) for 30 min did not affect IL-6 levels. CONCLUSIONS: ET-1 impairs endothelium-dependent and -independent vasodilatation and stimulates release of IL-6 in humans in vivo. These effects are inhibited by pre-treatment with the antioxidant Vitamin C. This suggests that the mechanism by which ET-1 impairs vascular function and stimulates release of IL-6 involves increased oxidative stress.