A Reappraisal of the Safety and Cost-Effectiveness of Statin Therapy in Primary Prevention.

Statins are among the most investigated drugs of all time. There is now a wealth of evidence supporting their use in the primary and secondary prevention arenas. The reduction in event recurrence has since been demonstrated across all levels of risk and in elderly patients.

Ultrasound entropy may be a new non-invasive measure of pre-clinical vascular damage in young hypertensive patients.

Background: The identification of pre-clinical microvascular damage in hypertension by non-invasive techniques has proved frustrating for clinicians. This proof of concept study investigated whether entropy, a novel summary measure for characterizing blood velocity waveforms, is altered in participants with hypertension and may therefore be useful in risk stratification.

Methods: Doppler ultrasound waveforms were obtained from the carotid and retrobulbar circulation in 42 participants with uncomplicated grade 1 hypertension (mean systolic/diastolic blood pressure (BP) 142/92 mmHg), and 26 healthy controls (mean systolic/diastolic BP 116/69 mmHg).

Endothelial Function in Hypertension: Victim or Culprit?

Far from simply lining the inner surface of blood vessels, the cellular monolayer that comprises the endothelium is a highly active organ that regulates vascular tone. In health, the endothelium maintains the balance between opposing dilator and constrictor influences, while in disease, it is the common ground on which cardiovascular risk factors act to initiate the atherosclerotic process. As such, it is the site at which cardiovascular disease begins and consequently acts as a barometer of an individual's likely future cardiovascular health.

Wavelet entropy of Doppler ultrasound blood velocity flow waveforms distinguishes nitric oxide-modulated states.

Wavelet entropy assesses the degree of order or disorder in signals and presents this complex information in a simple metric. Relative wavelet entropy assesses the similarity between the spectral distributions of two signals, again in a simple metric. Wavelet entropy is therefore potentially a very attractive tool for waveform analysis.

Platelet redox balance in diabetic patients with hypertension improved by n-3 fatty acids.

Objective: Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing cardiovascular disease, largely as a result of defective production of cardioprotective nitric oxide and a concomitant rise in oxidative stress. Dietary interventions that could reverse this trend would be extremely beneficial. Here we investigated whether dietary n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation positively affected platelet nitroso-redox imbalance.

Impaired microvascular properties in uncomplicated type 1 diabetes identified by Doppler ultrasound of the ocular circulation.

Objective: Quantification of Doppler flow velocity waveforms has been shown to predict adverse cardiovascular outcomes and identify altered downstream haemodynamics and vascular damage in a number of organ beds. We employed novel techniques to quantify Doppler flow velocity waveforms from the retro bulbar circulation.

Methods And Results: In total, 39 patients with uncomplicated Type 1 diabetes mellitus, and no other significant cardiovascular risk factors were compared with 30 control subjects.

Ocular blood flow analysis detects microvascular abnormalities in impaired glucose tolerance.

Objective: Waveform analysis has been used to assess vascular resistance and predict cardiovascular events. We aimed to identify microvascular abnormalities in patients with IGT using ocular waveform analysis. The effects of pioglitazone were also assessed.

Impaired flow-mediated dilatation response in uncomplicated Type 1 diabetes mellitus: influence of shear stress and microvascular reactivity.

Impaired FMD (flow-mediated dilatation) has traditionally been recognized as an indirect marker of NO bioactivity, occurring in disease states such as DM (diabetes mellitus). Endothelium-dependent FMD is a homoeostatic response to short-term increases in local shear stress. Microvascular dysfunction in DM influences blood flow velocity patterns.

Statins in heart failure-where do we stand?

HMG Co-A reductase inhibitors (statins) are a group of drugs which lower cholesterol by inhibiting the conversion of HMG Co-A to mevalonate early in the cholesterol synthetic pathway. They are used in the primary and secondary prevention of cardiovascular events in patients deemed to be at increased risk and their benefit in patients with ischaemic heart disease is well supported. Their use in patients with heart failure (HF) however, is controversial.

Docosahexaenoic acid improves the nitroso-redox balance and reduces VEGF-mediated angiogenic signaling in microvascular endothelial cells.

Purpose: Disturbances to the cellular production of nitric oxide (NO) and superoxide (O(2)(-)) can have deleterious effects on retinal vascular integrity and angiogenic signaling. Dietary agents that could modulate the production of these signaling molecules from their likely enzymatic sources, endothelial nitric oxide synthase (eNOS) and NADPH oxidase, would therefore have a major beneficial effect on retinal vascular disease. The effect of ω-3 polyunsaturated fatty acids (PUFAs) on angiogenic signaling and NO/superoxide production in retinal microvascular endothelial cells (RMECs) was investigated.

Statins have beneficial effects on platelet free radical activity and intracellular distribution of GTPases in hyperlipidaemia.

In addition to lowering cholesterol, statins may alter endothelial release of the vasodilator NO and harmful superoxide free radicals. Statins also reduce cholesterol intermediates including isoprenoids. These are important for post-translational modification of substances including the GTPases Rho and Rac.

End-organ dysfunction and cardiovascular outcomes: the role of the microcirculation.

Risk factors for cardiovascular disease mediate their effects by altering the structure and function of wall and endothelial components of arterial blood vessels. A pathological change in the microcirculation plays a pivotal role in promoting end-organ dysfunction that not only predisposes to further organ damage, but also increases the risk for future macrovascular events. The microcirculation is recognized as the site where the earliest manifestations of cardiovascular disease, especially inflammatory responses, occur that may play a pivotal role in driving the atherosclerotic process in conduit vessels.

A cardiologist view of vascular disease in diabetes.

Diabetes mellitus is a potent risk factor for the development of a wide spectrum of cardiovascular (CV) complications. The complex metabolic milieu accompanying diabetes alters blood rheology, the structure of arteries and disrupts the homeostatic functions of the endothelium. These changes act as the substrate for end-organ damage and the occurrence of CV events.

Arterial stiffness: clinical relevance, measurement and treatment.

Most traditional cardiovascular risk factors alter the structure and/or function of arteries. An assessment of arterial wall integrity could therefore allow accurate prediction of cardiovascular risk in individuals. The term 'arterial stiffness' denotes alterations in the mechanical properties of arteries, and much effort has focused on how best to measure this.

Subclinical impairment of arterial mechanics in systemic lupus erythematosus identified by arterial waveform analysis.

Structural and functional changes in wall and endothelial components of arterial blood vessels underlie the accelerated vascular disease progression in systemic lupus erythematosus (SLE). Using pulse contour analysis we sought to determine if subclinical vascular abnormalities could be identified in a well-characterised cohort of patients with SLE who had no increase in traditional cardiovascular risk factors. Radial artery pressure waveforms were obtained by applanation tonometry and pressure envelopes were analysed by descriptive and model-based approaches.

Measuring endothelial function.

Dysfunction of the endothelium and of the arterial wall is well described in patients with atherosclerosis, diabetes, and other risk factors for vascular disease. In recent years, clinical research has focused on elucidating the role of this dysfunction in influencing vascular disease progression. Alteration in the structure of arteries and disruption of the homeostatic functions of the endothelium act as a substrate for end-organ damage and the occurrence of vascular events.

Microcirculatory hemodynamics and endothelial dysfunction in systemic lupus erythematosus.

Objective: Impaired flow-mediated dilation (FMD) occurs in disease states associated with atherosclerosis, including SLE. The primary hemodynamic determinant of FMD is wall shear stress, which is critically dependent on the forearm microcirculation. We explored the relationship between FMD, diastolic shear stress (DSS), and the forearm microcirculation in 32 patients with SLE and 19 controls.

Nitric oxide modulation of ophthalmic artery blood flow velocity waveform morphology in healthy volunteers.

Quantitative analysis of the arterial pressure pulse waveform recorded by applanation tonometry of the radial artery can track NO (nitric oxide)-mediated modulation of arterial smooth muscle tone. The changes in pressure pulse waveform morphology result from pulse wave reflection arising predominantly from smaller arteries and arterioles. Employing Doppler ultrasound to record the spectral flow velocity waveform in the ophthalmic artery, we studied the effects of NO modulation on waveforms recorded in the proximity of the terminal ocular microcirculatory bed.

Effects of dietary omega-3 fatty acid supplementation on endothelium-dependent vasodilation in patients with chronic heart failure.

We investigated the effects of omega-3 fatty acids administration on endothelium-dependent vasodilation in patients > or =65 years old who received treatment for chronic heart failure (CHF). Twenty patients (mean age 73 years; 15 men) with grade II and III CHF who were on maximal medical management were recruited. Patients were randomized in a double-blind, crossover fashion to 6 weeks of omega-3 fatty acid (1.

Increased superoxide production in hypertensive patients with diabetes mellitus: role of nitric oxide synthase.

Background: Hypertension and diabetes are important independent risk factors for increased oxidative stress and increased cardiovascular risk. The combination of hypertension and diabetes results in a dramatic increase in cardiovascular risk. Enhanced oxidative stress in hypertension and diabetes is linked to decreased nitric oxide (NO) bioavailability because of its interaction with vascular superoxide (O(2)(*-)), derived predominantly from NAD(P)H-dependent oxidases.

NAD(P)H-dependent superoxide production in platelets: the role of angiotensin II and protein kinase C.

Objectives: Vascular NAD(P)H oxidase represents a major source for excessive superoxide production in hypertension. Angiotensin II (AngII) can activate NAD(P)H oxidase via the angiotensin II type 1 (AT1) receptor and protein kinase C (PKC). Platelets possess AT1 receptors and all the components of the NAD(P)H oxidase system.

Impaired endothelium-dependent and -independent vasodilation in elderly patients with chronic heart failure.

Background: Impaired endothelium-dependent and independent vasodilator responses in chronic heart failure (CHF) have been well described. Previous studies involved younger patients and omitted medications prior to study.

Aims: We explored if new therapeutic interventions would restore vasodilator responses in typical patients with chronic heart failure.

Vascular abnormalities in hypertension: cause, effect, or therapeutic target?

Alteration in the physical properties of arterial blood vessels act as the substrate for end-organ damage and the occurrence of vascular events in hypertension. Structural and functional alteration in the microcirculation represents a prevalent and characteristic abnormality described in the earliest stages of hypertension. In addition to lowering arterial pressure, the importance of reversing structural abnormalities and restoring endothelial function has recently been emphasized.