Carla Sala

Sympathetic Activation and Loss of Reflex Sympathetic Control in Mild Congestive Heart Failure

BACKGROUND Baroreflex control of sympathetic activity is impaired in severe congestive heart failure (CHF), probably causing the marked sympathetic activation typical of this condition. Little information exists, however, as to whether baroreflex impairment and related sympathetic activation also occur in mild CHF. METHODS AND RESULTS We studied 19 patients (age, 57.5 +/- 2.2 years, mean +/- SEM) with CHF in New York Heart Association (NYHA) class III or IV and with a marked reduction in left ventricular ejection fraction (LVEF, 30.1 +/- 1.5% from echocardiography) and 17 age-matched patients with CHF in NYHA class I or II and with an only slightly reduced LVEF (44.9 +/- 3.3%) that never was < 40%. Seventeen age-matched healthy subjects served as control subjects. Primary measurements included beat-to-beat arterial blood pressure (with the Finapres technique), heart rate (from ECG), and postganglionic muscle sympathetic nerve activity (MSNA, from microneurography at the peroneal nerve). Measurements were performed at baseline and during baroreceptor stimulation (intravenous phenylephrine infusion), baroreceptor deactivation (intravenous nitroprusside infusion), and cold-pressor test. Baseline blood pressure was similar in the three groups, whereas heart rate was progressively greater from control subjects to patients with mild and severe CHF, MSNA (bursts per 100 heart beats) increased significantly and markedly from control subjects to patients with mild and severe CHF (47.1 +/- 2.9 versus 64.4 +/- 6.2 and 82.1 +/- 3.4, P < .05 and P < .01, respectively). Heart rate and MSNA were progressively reduced by phenylephrine infusion and progressively increased by nitroprusside infusion. Compared with control subjects, the responses were strikingly impaired in severe CHF patients, but a marked impairment also was seen in mild CHF patients. On average, baroreflex sensitivity in mild CHF patients was reduced by 59.1 +/- 5.5% (MSNA) and 64.8 +/- 4.8% (heart rate). In contrast, reflex responses to the cold-pressor test were similar in the three groups. CONCLUSIONS These results demonstrate that in mild CHF patients the baroreceptor inhibitor influence on heart rate and MSNA is already markedly impaired. This impairment may be responsible for the early sympathetic activation that occurs in the course of CHF.

Antihypertensive and renal effects of orally administered verapamil

SummaryIn 12 in-patients with moderate uncomplicated hypertension, maintained on constant sodium intake for 15 days, single-blind oral administration of verapamil 80–160 mg t. i. d. for 10 days had a significant antihypertensive effect: in the supine position systolic blood pressure decreased from 177±5 to 150±3 mmHg, and diastolic pressure from 111±3 to 96±2 mmHg; standing values were similarly lowered from 171±7 to 143±4 mmHg, systolic, and from 118±4 to 97±2 mmHg, diastolic. The heart rate did not show any significant change (from 79±3 to 77±2 beats/min, supine, and from 92±3 to 87±3 beats/min, upright). The antihypertensive effect was uniform throughout the day, being similar 2, 3, 6 and 8 h after administration of a dose. Dynamic exercise (75–100 watts on a cycle-ergometer) caused identical increases in arterial pressure and heart rate on the last day of placebo and again on the last day with verapamil, but the peak levels of systolic pressure reached during exercise were lower after verapamil than with placebo, because of the lower blood pressure before exercise. Reduction of arterial pressure by verapamil was not accompanied by increased plasma renin activity, or by renal retention of sodium and water: there was a small increase in sodium excretion, at least during the first days of verapamil administration (from 107±15 to 113±15 mEq Na+/day), and a slight significant reduction in body weight (from 74.2±3.7 to 73.5±3.7 kg). It is concluded that oral administration of verapamil significantly lowers blood pressure without simultaneously inducing cardiac stimulation, renin secretion or salt and water retention.

Prevalence of left-ventricular hypertrophy in hypertension: an updated review of echocardiographic studies

Left-ventricular hypertrophy (LVH) is a cardinal manifestation of hypertensive organ damage associated with an increased cardiovascular (CV) risk. We reviewed recent literature on the prevalence of LVH, as assessed by echocardiography, in order to offer an updated information on the magnitude of subclinical alterations in LV structure in contemporary human hypertension. A MEDLINE search using key words ‘left ventricular hypertrophy’, ‘hypertension’, ‘echocardiography’ and ‘cardiac organ damage’ was performed in order to identify relevant papers. Full articles published in English language in the last decade, (1 January 2000–1 December 2010), reporting studies in adult or elderly individuals, were considered. A total of 30 studies, including 37 700 untreated and treated patients (80.3% Caucasian, 52.4% men, 9.6% diabetics, 2.6% with CV disease) were considered. LVH was defined by 23 criteria; its prevalence ranged from 36% (conservative criteria) to 41% (less conservative criteria) in the pooled population. LVH prevalence was not different between women and men (range 37.9–46.2 versus 36.0–43.5%, respectively). Eccentric LVH was more frequent than concentric hypertrophy (range 20.3–23.0 versus 14.8–15.8, respectively, P<0.05); concentric phenotype was found in a consistent fraction (20%) of both genders. Despite the improved management of hypertension in the last two decades, LVH remains a highly frequent biomarker of cardiac damage in the hypertensive population. Our analysis calls for a more aggressive treatment of hypertension and related CV risk factors leading to LVH.

Prevalence and correlates of aortic root dilatation in patients with essential hypertension : relationship with cardiac and extracardiac target organ damage

Objective To assess the prevalence of aortic root dilatation in a large cohort of uncomplicated hypertensive patients and to evaluate the relations of aortic root size to different markers of cardiac and extracardiac target organ damage (TOD). Methods A total of 3366 untreated and treated essential hypertensive patients (mean age, 53 ± 12 years) consecutively attending our out-patient hypertension clinic and included in the Evaluation of Target Organ Damage in Hypertension (an observational ongoing registry of hypertension-related TOD) were considered for this analysis. All patients underwent routine examinations, 24-h urine collection for microalbuminuria, echocardiography and carotid ultrasonography. Results Aortic root dilatation, defined by the sex-specific echocardiographic criteria of 40 mm in men and 38 mm in women, was present in 8.5% of men and in 3.1% of women. Compared with 3160 patients with normal aortic size, the group of 206 patients with an enlarged aortic root was older, had higher diastolic blood pressure values and included a greater fraction of subjects under antihypertensive treatment, with type 2 diabetes and metabolic syndrome. The prevalence of left ventricular hypertrophy, carotid intima–media thickening, plaques and microalbuminuria was significantly higher in patients with aortic root dilatation. According to a logistic regression analysis, left ventricular hypertrophy, carotid atherosclerosis, overweight and metabolic syndrome were the main independent and potentially modifiable predictors of aortic root dilatation in the whole hypertensive population as well as in untreated and treated hypertensive patients separately. Conclusions Our study shows that hypertensive patients with aortic root enlargement have more pronounced alterations in cardiac structure and geometry as well as in carotid artery morphology compared with those without the enlargement. Aortic root dilatation therefore appears to be a useful marker of high cardiovascular risk related to TOD. Whether this alteration independently predicts cardiovascular morbidity remains to be proven.

Short-term reproducibility of a non-dipping pattern in type 2 diabetic hypertensive patients.

Background Little information is available on the reproducibility of nocturnal variations in blood pressure in type 2 diabetic hypertensive patients. Objective We aimed to compare the intrasubject short-term reproducibility of a nocturnal non-dipping pattern and the prevalence of cardiac and extracardiac signs of target organ damage, in a group of type 2 diabetic hypertensive patients and in an age/gender-matched group of non-diabetic hypertensive subjects. Methods Thirty-six treated hypertensive patients with long-lasting type 2 diabetes (> 10 years duration) consecutively attending our hospital out-patient hypertension clinic (group I; mean age, 65 ± 9 years), and 61 untreated non-diabetic subjects with grade 1 and grade 2 uncomplicated essential hypertension, matched for age and gender, and chosen from patients attending an outpatient clinic (group II; mean age, 65 ± 5 years), were considered for this analysis. All patients underwent blood sampling for routine blood chemistry, 24-h urine collection for microalbuminuria, two 24-h periods of ambulatory blood pressure monitoring (ABPM) within a 4-week period, echocardiography, and carotid ultrasonography. A dipping pattern was defined as a greater than 10% reduction in the average systolic and diastolic blood pressure at night compared with average daytime values. Results A reproducible nocturnal dipping and non-dipping profile was found in 11 (30.6%) and 21 (58.3%) diabetic patients, respectively; while only in four (11.1%) patients was a variable dipping profile observed. Of the 23 patients with a non-dipping pattern during the first ABPM period, 21 (91.3%) also had this type of pattern during the second ABPM recording. In group II (non-diabetic hypertensive patients), 30 patients (49.2%, P < 0.05) had a dipping pattern, 13 patients (21.3%, P < 0.01) had a non-dipping profile pattern and 18 patients (29.5%, P < 0.01) had a variable dipping pattern. Of the 20 patients with a non-dipping pattern during the first ABPM period, 13 (65.0%) confirmed this type of pattern during the second ABPM recording. Finally, the prevalence of left ventricular hypertrophy (77.7 versus 41.4%, P < 0.01), carotid plaques (80.5 versus 38.3%, P < 0.01), carotid intima–media thickening (54.3 versus 44.0%, P < 0.05) and microalbuminuria (11.1 versus 2.0%, P < 0.01) was significantly higher in group I than in group II. According to a logistic regression analysis, diabetes, left ventricular hypertrophy and carotid plaques were the main independent predictors of the non-dipping (pattern in the overall population. Conclusions These findings indicate that intrasubject variability of non-dipper pattern is lower in diabetic than in non-diabetic hypertensive patients, that classification of diabetic hypertensive patients as dipper or non-dipper on the basis of a single ABP recording is more reliable than in non-diabetic patients, and that the more frequent and reproducible non-dipping (pattern in diabetic patients is associated with a more prominent cardiac and extracardiac target organ damage.

Left-ventricular hypertrophy and obesity: a systematic review and meta-analysis of echocardiographic studies.

Aim: Left-ventricular hypertrophy (LVH) is a frequent complication in obese individuals; an updated review and meta-analysis focusing on this issue is lacking. Thus, we analysed the literature in order to provide a comprehensive information on the left-ventricular structural changes, as assessed by echocardiography, associated to obesity. Design: A literature search using the keywords ‘left ventricle’, ‘left-ventricular hypertrophy’, ‘cardiac hypertrophy’, ‘obesity’, ‘hypertension’ and ‘echocardiography’ was performed in order to identify relevant papers. Full articles published in English language in the past 12 years reporting studies in adult obese individuals were considered. Results: A total of 22 studies including 5486 obese individuals were considered. Overall, in the pooled obese population, prevalence of LVH, defined by 12 criteria, was 56.0% (range 20.0–85.0%). Data provided by 15 studies (n = 4999 obese individuals), including 6623 non-obese controls, showed that the probability of having LVH was much higher in cases than in non-obese counterparts (odds ratio 4.19, 95% confidence interval 2.67–6.53, P < 0.01). A meta-regression analysis (n = 2214; 14 studies) showed a direct correlation between BMI and left-ventricular mass (P < 0.01). Among obese patients with LVH (n = 1930; 15 studies), eccentric hypertrophy was more frequent than the concentric phenotype (66 versus 34%; P < 0.01). Conclusions: Our analysis shows that LVH is present in a consistent fraction of the obese population and that eccentric hypertrophy prevails over the concentric phenotype. As obesity-related LVH is a powerful risk factor for systolic/diastolic dysfunction, the prevention/treatment of obesity may have a strong, favourable impact on incident heart failure.

Atrial Natriuretic Peptide and Hemodynamic Changes During Normal Human Pregnancy

We compared plasma atrial natriuretic peptide (ANP) and cGMP levels during normal pregnancy--a condition characterized by hypervolemia, high cardiac output, and decreased vascular resistance--with postpartum levels and assessed their relation to pregnancy-induced hemodynamic changes. Humoral and hemodynamic variables were measured in healthy women subjects in the supine and upright postures at each trimester of pregnancy and postpartum. Supine plasma ANP was increased throughout pregnancy (32 +/- 5, 21 +/- 3, and 19 +/- 2 versus 15 +/- 1 pmol.L-1, respectively, at each trimester versus postpartum), as was cGMP (8.6 +/- 1, 7.1 +/- 1, and 6.6 +/- 1 versus 5.6 +/- 1 nmol.L-1), and their increments were directly related (r = .68, P < .01). Both ANP and cGMP levels did not differ from postpartum levels after subjects stood. Supine stroke volume was initially increased but declined below postpartum levels in late pregnancy (69 +/- 4, 60 +/- 3, and 44 +/- 3 versus 58 +/- 4 mL.m-2), whereas after subjects stood it was always higher (56 +/- 3, 58 +/- 3, and 49 +/- 2 versus 44 +/- 2 mL.m-2); thus, stroke volume tended to increase in response to standing in late pregnancy. Supine cardiac index had a similar trend, which was opposite to that of total peripheral resistance (1213 +/- 62, 1265 +/- 79, and 1729 +/- 89 versus 1654 +/- 92 dyne.s-1.cm-5.m-2).(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular hypertrophy and cardiovascular risk stratification: Impact and cost-effectiveness of echocardiography in recently diagnosed essential hypertensives

Background Echocardiography is more accurate than electrocardiography in the assessment of cardiac target organ damage related to hypertension, thus leading to a more precise stratification of total cardiovascular risk. However, ultrasound examination of the heart on a routine basis remains a matter of debate. Objective To evaluate the impact and cost-effectiveness of echocardiographic examination on global risk stratification in low and medium-risk hypertensive patients in relation to age and sex. Methods A total of 580 untreated hypertensive individuals (355 men and 225 women, mean age 47.8 ± 11.4 years), classified at low to medium risk, according to routine clinical work-up suggested by the 2003 European Society of Hypertension/European Society of Cardiology guidelines, were included in the study. Total risk was reassessed by adding the results of ultrasound examination of the heart. Left ventricular hypertrophy (LVH) was defined as a left ventricular mass index of 125 g/m2 or more in men and 110 g/m2 or more in women. The impact of LVH in stratifying risk was assessed according to age (< 50 and ≥ 50 years) and sex. Results According to routine classification, 16.3% (n = 93) of the 580 patients were considered to be at low added risk and 83.7% (n = 487) at medium added risk. In the whole population, echocardiographic LVH was found in 86 patients (14.8%) who were then reclassified in the high-risk stratum. The prevalence rates of patients reclassified in the high-risk class as a consequence of LVH detection, according to age and sex, were as follows: 8.9% in men under 50 years, 12.3% in women under 50 years, 26.7% in men aged 50 years and over and 15.3% in women aged 50 years and over. The cost per detected case of LVH was &U20AC;595 in patients under 50 years of age and &U20AC;290 in those 50 years of age and older. Conclusions Our findings indicate that the prevalence of LVH, and consequently the probability of upgrading the total cardiovascular risk profile, is highest in the group of old hypertensive men; echocardiography has a limited impact on the risk reclassification in younger patients and an unfavourable cost-effectiveness profile. Our data thus do not support the systematic ultrasound assessment of the heart in all uncomplicated hypertensive individuals.

White-coat hypertension, as defined by ambulatory blood pressure monitoring, and subclinical cardiac organ damage: a meta-analysis.

Aim: The clinical and prognostic relevance of white-coat hypertension (WCH) has not been fully elucidated; in particular, the association of this blood pressure phenotype with suclinical organ damage remains unclear. We performed a systematic meta-analysis in order to provide a comprehensive information on cardiac structural and functional changes in WCH, as defined by ambulatory blood pressure monitoring. Design: Studies were identified by the following search terms: ‘white-coat hypertension’, ‘isolated clinic hypertension’, ‘cardiac organ damage’, ‘target organ damage’, ‘left ventricle’, ‘left ventricular hypertrophy’, ‘cardiac hypertrophy’, ‘ventricular dysfunction’, and ‘echocardiography’. Results: A total of 7382 untreated adult patients (2493 normotensive, 1705 WCH, and 3184 hypertensive individuals) included in 25 studies were considered. Left ventricular mass index was higher in WCH than in normotensive patients [standardized difference in mean (SDM) 0.50, P < 0.01]; mitral E/A ratio was lower (SDM −0.27, P < 0.01) and left atrium larger (SDM 0.29, P < 0.05) in WCH than in the normotensive counterparts. Hypertensive patients showed a greater left ventricular mass index (SDM 0.42, P < 0.01), reduced E/A (SDM −0.15, P < 0.01), and larger left atrium diameter (SDM 0.27, P < 0.01) than WCH patients. Conclusions: Our meta-analysis shows that alterations in cardiac structure and function in WCH patients, as defined by ambulatory blood pressure monitoring, are intermediate between sustained hypertensive patients and normotensive controls. The study supports the view that WCH should not be further considered a fully benign entity.

Nocturnal hypertension and organ damage in dippers and nondippers

BACKGROUND The relationship between high nocturnal blood pressure (BP), organ damage and the dipping/nondipping status is poorly defined. We investigated whether a consistent dipping/nondipping pattern defined on the basis of two 24-h ambulatory BP monitorings (ABPMs) is associated with subclinical organ damage in untreated hypertensive patients with elevated nighttime BP. METHODS All subjects underwent the following procedures: cardiac and carotid ultrasonography, 24-h urine collection for microalbuminuria (MA), and ABPM over two 24-h periods within 4 weeks. Nocturnal hypertension was defined according to current guidelines (i.e., nighttime systolic BP (SBP) ≥120 and/or diastolic BP ≥70 mm Hg) and nondipping status as an average reduction in SBP at night <10% compared with day-time values. RESULTS Among 343 subjects, 199 were dippers and 144 nondippers. No differences were found in clinical variables, average 48-h BP, left ventricular mass, carotid intima-media (IM) and urinary albumin excretion between the groups. This was also the case for prevalence rates of left ventricular hypertrophy, carotid IM thickening or plaque and MA. Finally, no relationship was found between the markers of organ damage and BP fall at night. CONCLUSIONS In the presence of nocturnal hypertension, dippers have a similar subclinical cardiac and extra-cardiac organ damage as their nondipper counterparts. These data suggest that therapeutic strategies only addressing the nondipper pattern may be insufficient to protect hypertensive subjects against the dangerous effects of elevated nocturnal BP.American Journal of Hypertension, (2012); doi:10.1038/ajh.2012.49.