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Biomedical subjects

Guido Grassi

Publications and source records attributed to Guido Grassi.

At least 55 records · Page 3Linked to original sources
PubMed2004

Effect of central and peripheral body fat distribution on sympathetic and baroreflex function in obese normotensives.

BACKGROUND: Previous studies have shown that obesity is characterized by a sympathetic overactivity coupled with an insulin resistance state and a baroreflex impairment. The present study was set out to compare the effects of peripheral versus central obesity on sympathetic, metabolic and reflex function. METHODS: In 36 lean subjects (age 35.8 +/- 1.4 years, mean +/- SEM), 20 subjects with peripheral obesity (PO) and 26 subjects with central obesity (CO), all age-matched and with normal blood pressure values, we measured beat-to-beat arterial blood pressure (Finapres), heart rate (HR, ECG), homeostasis model assessment (HOMA) index, plasma norepinephrine (NE, high-performance liquid chromatography) and postganglionic muscle sympathetic nerve traffic (MSNA, microneurography) at rest and during baroreceptor stimulation and deactivation induced by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. RESULTS: Both HOMA index, NE and MSNA values were significantly increased (P < 0.01) in obese as compared with lean individuals. Subjects with CO displayed MSNA and HOMA values significantly greater than those found in individuals with PO (65.4 +/- 2.0 versus 47.9 +/- 1.9 bs/100hb and 2.85 +/- 0.10 versus 2.43 +/- 0.11 a.u., respectively, P < 0.05 for both). Both in male and female subjects with CO or PO, MSNA, HOMA index and waist-to-hip ratio were significantly related to each other. Baroreceptor-HR and -MSNA control was significantly (P < 0.01) impaired in obese as compared with lean subjects, the degree of impairment being similar in CO and PO. CONCLUSIONS: These data suggest that CO is characterized by a sympathetic activation greater for magnitude than that detectable in PO. This appears not to be related to gender or to baroreflex mechanisms but rather to metabolic factors, i.e. to the greater insulin resistance characterizing CO.

Adult↗
PubMed2004

Blood pressure control according to new guidelines targets in low- to high-risk hypertensives managed in specialist practice.

OBJECTIVE: It is well established that adequate blood pressure (BP) control characterizes only a fraction of treated hypertensive patients. Few reports are available on BP control in relation to the cardiovascular risk profile in patients followed by specialist physicians. METHODS: We evaluated the cardiovascular risk profile (according to recent ESH/ESC Guidelines), antihypertensive drug treatment and systolic and diastolic blood pressure values (SBP/DBP) by semi-automatic BP monitoring in 2775 hypertensive patients, aged 60.6 +/- 16.1 years (mean +/- SD), followed by 131 specialist centres in northern (34.5%), central (28.1%) and southern (37.4%) Italy. Of these patients, 94.6% received antihypertensive treatment with one (36.9%) or more (57.7%) drugs. RESULTS: Optimal SBP and DBP control (< 140/90 mmHg) was shown by 37.5% of the patients, the rate of controlled values being much greater for DBP (64.4%) than for SBP (40.2%). About one-third of patients displayed BP values in the higher range (>/= 160/95 mmHg). No difference in BP control was found in relation to different geographic areas, patient's gender, occupational activity and attitude to the use of home blood pressure monitoring. BP control was inversely related to patient's age and directly related to educational level. It was more manifest in low- or medium-risk categories than in higher-risk patients (43.2 versus 34.9%). Follow-up visits performed after 6 and 12 months after patient enrollment have shown an improvement in blood pressure control (from 40.7 to 51.8%), related to therapeutic modifications and better compliance. CONCLUSIONS: These data provide evidence that BP control in different Italian geographic areas remains largely inadequate, particularly for SBP and high-risk patients. They also suggest that an improvement in treatment compliance may produce favourable therapeutic effects.

Adult↗
PubMed2004

Effects of the combination of low-dose nifedipine GITS 20 mg and losartan 50 mg in patients with mild to moderate hypertension.

Most hypertensive patients require more than one medication to effectively control elevated blood pressure (BP) values. This multicenter, randomized, double-blind study was aimed at testing the efficacy and safety of the combination of low-dose nifedipine GITS 20 mg/ losartan 50 mg compared with either monotherapy in patients with grade 1 to 3 hypertension over an eight-week period. Of 352 patients enrolled in the study, 300 were randomized. All the three treatments lowered elevated BP without clinically relevant changes in heart rate. All the three treatments lowered mean 24-hour diastolic BP: nifedipine GITS/losartan -10.6 mm Hg, losartan -5.4 mm Hg, nifedipine GITS 20 mg -8.0 mm Hg. There was a statistically significant difference of diastolic BP change between patients receiving losartan compared with those receiving combination treatment (P < 0.05). Diastolic BP trough-to-peak ratio and smoothness index were highest in the patient group receiving combination therapy (70%). Nifedipine GITS monotherapy had the highest systolic BP trough-to-peak ratio of all treatment arms (78%) and higher diastolic BP trough-to-peak ratio and smoothness index than losartan monotherapy. All treatments were safe. These data provide evidence that in hypertensive patients combination of nifedipine GITS 20 mg and losartan 50 mg improves control of systolic and diastolic BP compared with either monotherapy.

Adult↗
PubMed2004

Counteracting the sympathetic nervous system in essential hypertension.

PURPOSE OF REVIEW: This paper will provide an up-to-date overview of the adrenergic effects of the different classes of antihypertensive drugs in uncomplicated hypertension, as well as in hypertension associated with obesity, renal failure, diabetes or congestive heart failure. RECENT FINDINGS: Animal and human studies unequivocally show that sympathetic activation characterizes the hypertensive state and participates in the development, maintenance and progression of elevated blood pressure values. Evidence has also been provided that elevated sympathetic cardiovascular influences are involved in the pathogenesis of left ventricular hypertrophy, vascular hypertrophy and atherogenesis, as well as in the occurrence of metabolic disarray (i.e. metabolic syndrome, hypercholesterolemia, hyperinsulinemia and insulin resistance), which frequently accompany the hypertensive state. Antihypertensive drugs with confirmed sympathoinhibitor effects are represented by beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. In the case of the latter two classes of antihypertensive compounds the sympathoinhibitory effects have been shown to be associated with beneficial metabolic and cardiovascular effects, a finding that supports the use of these drugs in complicated hypertension. SUMMARY: Investigation of the adrenergic effects of antihypertensive drugs has had a significant impact on cardiovascular pharmacology and hypertension treatment. Although remarkable progress has been made on this topic in recent years, future studies aimed at assessing the sympathetic effects of combination drug treatment will be helpful in improving the clinical use of the association of two or more drugs in hypertension treatment.

Angiotensin Receptor Antagonists↗
PubMed2004

Sympathetic and baroreflex function in hypertension: implications for current and new drugs.

The sympathetic nervous system has moved towards center stage in cardiovascular medicine. The importance of the sympathetic activation in heart failure and in renal insufficiency progression and mortality is indeed now well established. In essential hypertension evidence has been provided that this may be the case, because sympathetic overactivity is a key factor in the pathophysiology of the disease, thereby promoting not only the blood pressure increase but also the development and progression of the hypertension-related cardiovascular and metabolic complications, such as left ventricular hypertrophy, vascular hypertrophy, endothelial dysfunction, cardiac rhythm disturbances and insulin resistance. In this review article the main pathophysiologic and mechanistic features of the sympathetic overactivity characterizing the essential hypertensive state will be examined. This will be followed by an analysis of the effects of 1) the hyperadrenergic state on the cardiovascular risk profile as well as on the end organ damage and 2) the different antihypertensive compounds on sympathetic and baroreflex function. The rationale for obtaining during antihypertensive drug treatment an effective sympathoinhibition will be finally highlighted.

Animals↗
PubMed2003

Effects of hypertension and obesity on the sympathetic activation of heart failure patients.

Previous studies have shown that congestive heart failure is characterized by sympathetic and reflex dysfunctions. Whether these alterations are potentiated in the presence of obesity and hypertension, two conditions that also display neuroadrenergic abnormalities and markedly increase the risk of heart failure, is unknown. In 14 healthy control subjects (C; age, 55.1+/-3.0 years; mean+/-SEM), 13 lean hypertensive subjects (H), 15 obese normotensive subjects (O), 14 lean normotensive subjects with congestive heart failure (CHF, New York Heart Association class II), 14 lean hypertensive subjects with CHF (CHFH), 14 obese normotensive subjects with CHF (CHFO), and 13 obese hypertensive subjects with CHF (CHFOH), all age-matched with C, we measured mean blood pressure (Finapres), heart rate (ECG), and muscle sympathetic nerve traffic (MSNA, microneurography) at rest and during baroreflex testing. Compared with C, body mass index was similarly increased in O, CHFO, and CHFOH, whereas mean blood pressure was similarly increased in HF, CHFH, and CHFOH, and left ventricular ejection fraction (echocardiography) was similarly reduced in CHF, CHFH, CHFO and CHFOH. Compared with C, MSNA was significantly increased in O, H, and CHF (43.0+/-2.2 versus 54.1+/-2.8, 53.1+/-2.5, and 57.4+/-2.8 bursts/100 heart beats, P<0.01). When O or H was combined with CHF, the MSNA increase was significantly more pronounced and maximal when O and H were concomitantly associated with CHF. Baroreflex sensitivity was reduced in O and H, with a further reduction in CHF and a minimal value in CHFOH. These data show that the sympathetic activation characterizing CHF is markedly potentiated when O and H alone or combined together are associated with a low cardiac output state and that this may depend on an arterial baroreflex impairment.

Blood Pressure↗
PubMed2003

Impairment of thermoregulatory control of skin sympathetic nerve traffic in the elderly.

BACKGROUND: Human aging is characterized by a marked increase in muscle sympathetic nerve traffic (MSNA). No information exists, however, on the effects of aging on skin sympathetic nerve traffic (SSNA) and on its reflex modulation by thermoregulatory mechanisms. METHODS AND RESULTS: In 13 young, 11 middle-aged, and 12 elderly healthy subjects, we measured arterial blood pressure (Finapres), skin temperature (thermocouples), and resting MSNA and SSNA (microneurography). Measurements also included the SSNA responses to (1) an acute increase and reduction (+/-8 degrees C) in room temperature, each lasting 45 minutes and (2) an acoustic stimulus capable to trigger an emotional arousal. Although resting MSNA was progressively and significantly (P<0.05) increased from young to middle-aged and elderly groups, SSNA was significantly (P<0.05) reduced in the latter compared with the former 2 groups. Cold exposure induced a SSNA increase that was significantly (P<0.01) smaller in the elderly than in young and middle-aged subjects. Conversely, heat exposure induced a SSNA reduction that was significantly (P<0.05) smaller in elderly than in young and middle-aged subjects. Compared with SSNA in young individuals, the SSNA change from cold to warm temperature was reduced by 61% in the elderly group. This was not the case, however, for the SSNA responses to the arousal stimulus, which were superimposable in the 3 groups. CONCLUSIONS: These data provide the first demonstration of a dichotomy in the MSNA and SSNA responses to aging. They also show that aging markedly impairs thermoregulatory control of SSNA and that this impairment might participate at the age-related SSNA decrease.

Adolescent↗
PubMed2003

Purification and structural characterization of 3-hydroxypropionaldehyde and its derivatives.

The compound 3-hydroxypropionaldehyde (3-HPA), together with HPA hydrate and HPA dimer, in aqueous solution forms a system with interesting chemical properties. Therefore, 3-HPA has attracted attention by the chemical industry for use as a precursor in the production of plastics, acrylic acid, and 1,3-propanediol and by the food industry, in using 3-HPA-producing Lactobacillus reuteri as a probiotic. To produce 3-HPA in high yield from glycerol, L. reuteri was used as a biotransformation system. A convenient chromatographic purification method was developed, and purified 3-HPA was analyzed using electrospray ionization mass spectrometry and (13)C NMR. Quantitative (13)C NMR revealed a concentration-dependent distribution of the three compounds forming the HPA system. At concentrations above 1.4 M, the HPA dimer was predominant. However, at concentrations relevant for biological systems, HPA hydrate was the most abundant, followed by the aldehyde form. Our results indicate that the dimeric form with expected antibiotic properties should not be the active form.

Aldehydes↗
PubMed2003

Short-versus long-term effects of different dihydropyridines on sympathetic and baroreflex function in hypertension.

Antihypertensive treatment with dihydropyridines may be accompanied by sympathetic activation. Data on whether this is common to all compounds and similar in the various phases of treatment are not univocal, however. In 28 untreated essential hypertensives (age, 56.4+/-1.8 years; mean+/-SEM) finger blood pressure (BP, Finapres), heart rate (HR, ECG), plasma norepinephrine (NE, high-performance liquid chromatography), and muscle sympathetic nerve traffic (MSNA, microneurography) were measured at rest and during baroreceptor manipulation (vasoactive drugs) in the placebo run-in period and after randomization to double-blind acute and chronic (8 weeks) felodipine (10 mg/d, n=14) or lercanidipine (10 mg/d, n=14). Acute administration of both drugs induced pronounced BP reductions and marked increases in HR, NE, and MSNA. After 8 weeks of treatment, BP reductions were similar to those observed after acute administration, whereas HR, NE, and MSNA responses were markedly attenuated (-7%, -32%, and -14%, respectively; P<0.05). There was a small residual increase in sympathetic activity in the felodipine group, whereas in the lercanidipine group, all adrenergic markers returned to baseline values. Baroreflex control of HR and MSNA was markedly impaired (-42% and -48%, respectively) after acute drug administration, with a recovery and complete resetting during chronic treatment. Thus, the sympathoexcitation induced by 2 different dihydropyridines is largely limited to the acute administration. The 2 drugs have, nevertheless, a different chronic sympathetic effect, indicating that dihydropyridines do not homogeneously affect this function. The acute sympathoexcitation, but not the small between-drugs differential chronic adrenergic effect, is accounted for by baroreflex impairment.

Antihypertensive Agents↗
PubMed2003

Tolerability and treatment compliance with angiotensin II receptor antagonists.

Several studies and intervention trials performed during the past 30 years have provided evidence that hypertension-related cardiovascular risk is not irreversible. This is because the reduction in blood pressure (BP) induced by antihypertensive drugs has been shown to be accompanied by a clear-cut decrease in the rate of cardiovascular events and complications. There is also evidence that BP control in the population is far from being optimal, and that no more than one quarter of treated hypertensive patients display BP values <140/90 mm Hg. The reasons for inadequate BP control are multiple, involving a combination of factors such as inadequate compliance with treatment, intolerance to side effects of currently prescribed drugs, and insufficient clinical use of combination drug treatment. This article focuses on three major areas. It first provides an overview of the current status of BP control in treated hypertensive persons. It then examines the factors potentially responsible for this phenomenon, with particular emphasis on the relevance of the so-called "compliance factor." Finally it provides an overview of the tolerability and compliance profile of the angiotensin II receptor antagonists, a new class of antihypertensive drugs characterized by an efficacy and safety profile.

Angiotensin Receptor Antagonists↗
PubMed2003

Behaviour of the adrenergic cardiovascular drive in atrial fibrillation and cardiac arrhythmias.

AIM: Animal studies have conclusively shown that the sympathetic nervous system plays a major role not only in regulating sinus node activity but also in promoting cardiac rhythm alterations. Less univocal and often circumstantial have been the evidences collected on this issue in humans. However, the introduction of the microneurographic technique in clinical research has allowed to gain new important insights on the role of neuroadrenergic factors in the pathophysiology of cardiac arrhythmias. METHODS: The present paper will review the results of microneurographic studies performed by our group and others in the field of cardiac rhythm disturbances by addressing three specific issues. First it will examine the relationships between heart rate and muscle sympathetic neural outflow in a variety of cardiovascular diseases characterized by sympathetic activation. This will be followed by an analysis of the behaviour of the sympathetic nerve traffic responses to paroxysmal atrial fibrillation. Finally, the sympathetic adjustments to spontaneously occurring or artificially induced pre-mature ventricular contractions will be highlighted.

Atrial Fibrillation↗