The new concept of total cardiovascular risk management

Introduction: Cardiovascular risk factors, such as hypertension, hypercholesterolemia, and diabetes mellitus, often cluster together and can also be seen with other pathophysiological conditions that greatly increase an individual's risk for cardiovascular morbidity and death. Aim of the study: This article emphasizes the importance of assessing and managing the total cardiovascular risk in an individual patient. Materials and methods: Suggestions and recommendations from the most current hypertension management guidelines have been integrated with results from the major clinical trials published in the last decade. Results: Based on a review of the epidemiological data on cardiovascular disease, this paper expands the concept of stratification of hypertensive patients according to the approximate added risk of major cardiovascular events in the next 10 years and stresses the importance of subclinical target-organ damage. Conclusions: Although common in clinical practice, high-risk patients are often undiagnosed. Intensive hypertensive therapy is recommended for high-risk patients, and this treatment strategy will require combination therapy to control or reverse subclinical organ damage and prevent the progression of cardiovascular risk in subjects at low risk or medium risk

Effects of Chronic Clonidine Administration on Sympathetic Nerve Traffic and Baroreflex Function in Heart Failure

Abstract— Congestive heart failure is characterized by a sympathetic activation that is coupled with a baroreflex impairment. Whether these alterations are affected by clonidine is unknown. In 26 normotensive patients age 58.0±1.1 years (mean±SEM) affected by congestive heart failure (New York Heart Association functional class II or III) and treated with furosemide and enalapril, we measured mean arterial pressure, heart rate, venous plasma norepinephrine, and muscle sympathetic nerve traffic (microneurography) at rest and during baroreceptor stimulation and deactivation caused by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Measurements were repeated after a 2-month administration of transdermal clonidine patch (14 patients) or placebo (12 patients) according to a double-blind, randomized sequence. Clonidine caused a slight, nonsignificant reduction in mean arterial pressure and heart rate without affecting exercise capacity and echocardiographically determined left ventricular ejection fraction. In contrast, both plasma norepinephrine and sympathetic nerve traffic were significantly reduced (−46.8% and −26.7%, respectively; P <0.01 for both). This reduction was coupled with no change in cardiac and sympathetic baroreflex responses. Transdermal placebo administration for a 2-month period did not affect any of the above-mentioned variables. Thus, in congestive heart failure patients who are undergoing conventional drug treatment, chronic clonidine administration exerts marked sympathoinhibitory effects without adversely affecting cardiac functions and clinical state. Whether this leads to further therapeutic benefits remains to be tested

Effects of long-term lercanidipine or hydrochlorothiazide administration on hypertension-related vascular structural changes.

Vascular remodelling and hypertrophy represent early therapeutic targets of antihypertensive treatment. The present study was aimed at assessing the effects of 1-year administration of the highly vasoselective calcium-channel blocker lercanidipine (10 mg/day) or the diuretic compound hydrochlorothiazide (25 mg/day) on hypertension-related vascular alterations. The study was also aimed at assessing whether and to what extent: (i) pharmacological regression of vascular hypertrophy is related only to the blood pressure (BP) reduction "per se" or also to the specific ancillary properties of a given drug and (ii) treatment provides restoration of vascular function indicative of normal vascular structure.In 26 untreated patients with mild-to-moderate essential hypertension sphygmomanometric and finger BP, heart rate, forearm and calf blood flow (venous occlusion plethysmography) and corresponding vascular resistance (forearm and calf vascular resistance: FVR and CVR) were assessed before and following 6 and 12 months of either lercanidipine or hydrochlorothiazide administration. Vascular resistance was also evaluated following a local ischaemic stimulus (FVR(min) and CVR(min)) in order to assess the effects of treatment on arteriolar structural alterations.For superimposable BP reductions, lercanidipine caused FVR and CVR to decrease significantly more than hydrochlorothiazide. Similarly, the FVR(min) and CVR(min) reductions induced by lercanidipine were markedly and significantly greater than those caused by hydrochlorothiazide (-46.1% and -40.9% vs -22.5% and -19.9%, p0.01 for both). FVR(min), and CVR(min), however, remained higher than those found in 10 age-matched normotensive individuals.These data provide evidence that, compared to hydrochlorothiazide, lercanidipine favours a greater regression of the vascular structural changes associated with hypertension, probably through its "ancillary" properties. Lercanidipine, however, does not allow restoration of a "normal" vascular structure, thereby suggesting that vascular hypertrophy is only in part a reversible phenomenon

Short- and Long-Term Neuroadrenergic Effects of Moderate Dietary Sodium Restriction in Essential Hypertension

Background— In essential hypertension, marked restrictions in dietary sodium intake cause in the short-term period an increase in muscle sympathetic nerve traffic (MSNA) and a baroreflex impairment. The present study was set out to assess on a long-term basis the neuroadrenergic and reflex effects of moderate sodium restriction. Methods and Results— In 11 untreated mild to moderate essential hypertensive patients (age 42.0±2.6 years, mean±SEM), we measured beat-to-beat blood pressure (Finapres), heart rate (ECG), and MSNA (microneurography) at rest and during stepwise intravenous infusions of phenylephrine and nitroprusside. Measurements were performed at regular sodium intake, after 1 and 8 weeks of low-sodium diet (80 mmol NaCl/d), and repeated again at regular sodium intake. After 1 week, urinary sodium excretion was markedly reduced. This was accompanied by a slight blood pressure reduction, no heart rate change, and a significant increase in plasma renin activity, aldosterone, and MSNA (+23.0±4.6% P <0.05). Whereas baroreflex heart-rate control was unchanged, baroreflex modulation of MSNA was reduced by 46.8±5.1% ( P <0.01). At the end of the 8-week low-sodium diet, the neurohumoral and baroreflex responses were similar to the ones observed after 1 week of the dietary intervention. All changes disappeared when regular sodium diet was restored. Conclusions— Thus, a moderate dietary sodium restriction triggers a sympathetic activation and a baroreflex impairment. Maintenance of low-sodium diet for several weeks does not attenuate these adverse adrenergic and reflex effects

Sympathetic Control of Circulation in Hypertension and Congestive Heart Failure

Adrenergic overactivity is a common hallmark of both essential hypertension and congestive heart failure. Indirect and direct measures of sympathetic function have clearly shown that sympathetic activation characterizes essential hypertension. This adrenergic overactivity appears to be related to the severity of the hypertensive state, being detectable in its early stages and showing a progressive increase with the severity of the disease. Essential hypertension is also associated with an impaired baroreflex control of vagal activity, whereas baroreceptor modulation of sympathetic nerve traffic remains unaltered, although undergoing a resetting phenomenon. In contrast, secondary hypertension is not associated with an increased adrenergic activity, thus suggesting that an enhancement in efferent sympathetic outflow is a peculiar feature of essential hypertension. Congestive heart failure is a condition also characterized by sympathetic activation, whose degree is proportional to the clinical severity of the disease. This is paralleled by an impairment in arterial baroreceptor modulation of both vagal and sympathetic activity, thus suggesting that the adrenergic overactivity in congestive heart failure is triggered by a reduced afferent restraint on the vasomotor centre. Chronic angiotensin-converting enzyme inhibition reduces the degree of both sympathetic activation and baroreflex dysfunction occurring in heart failure patients, a finding which documents that the neurohumoral abnormalities can be at least partially reversed by pharmacologic treatment

Effects of somatostatin analogues on muscle sympathetic nerve activity in acromegaly

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The Complex Relationship Between Serum Uric Acid, Endothelial Function and Small Vessel Remodeling in Humans

Aims: The relationship between serum uric acid (SUA) and microvascular remodeling in humans remains largely unexplored. We assessed whether SUA provides additional information on the severity of microvascular remodeling than that obtained from the European Heart Score (HS), the patterns of microvascular remodeling associated with changes in SUA levels and the mediation by endothelial function and nitric oxide (NO) availability on this relationship. Methods: A total of 162 patients included in the microvascular dataset of the Italian Society of Hypertension with available information on SUA, media-to-lumen (M/L) ratio, media cross-sectional area (MCSA), endothelial function, NO availability and HS were included in the analysis. The top tertile of M/L ratio and MCSA were used to define severe microvascular remodeling. Results: A U-shaped association was observed between SUA and both M/L ratio and MCSA. Adjustment for HS did not affect these associations. SUA was able to reclassify a significant number of subjects without, and with, severe M/L ratio and MCSA remodeling over the HS alone. The microvascular remodeling associated with SUA levels presented a predominant hypertrophic pattern. SUA was inversely associated with endothelial function and NO availability. Structural equation modeling analysis controlling for the HS suggested that the association of SUA with M/L ratio and MCSA was mediated through changes in endothelial function and NO availability. Conclusions: The addition of SUA to the HS improves the identification of subjects with greater microvascular remodeling. The relationship between SUA and microvascular remodeling is mediated by endothelial function and NO availability

The new concept of total cardiovascular risk management

Introduction: Cardiovascular risk factors, such as hypertension, hypercholesterolemia, and diabetes mellitus, often cluster together and can also be seen with other pathophysiological conditions that greatly increase an individual’s risk for cardiovascular morbidity and death. Aim of the study: This article emphasizes the importance of assessing and managing the total cardiovascular risk in an individual patient. Materials and methods: Suggestions and recommendations from the most current hypertension management guidelines have been integrated with results from the major clinical trials published in the last decade. Results: Based on a review of the epidemiological data on cardiovascular disease, this paper expands the concept of stratification of hypertensive patients according to the approximate added risk of major cardiovascular events in the next 10 years and stresses the importance of subclinical target-organ damage. Conclusions: Although common in clinical practice, high-risk patients are often undiagnosed. Intensive hypertensive therapy is recommended for high-risk patients, and this treatment strategy will require combination therapy to control or reverse subclinical organ damage and prevent the progression of cardiovascular risk in subjects at low risk or medium risk