Closing remarks: current position of calcium channel antagonists in hypertension--the role of manidipine.
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Biomedical subjects
Publications and source records attributed to Alberto Zanchetti.
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Coarctation of the aorta is the fourth most frequent form of congenital cardiovascular disease, which is diagnosed by the presence of higher blood pressures in the arms than in the legs. In this report we describe 3 cases of aortic coarctation, in which the correct diagnosis was suspected only months or years after the detection of hypertension, when a renal ultrasound examination was requested, despite the fact that the hallmarks of the disease were present at the physical examination in all patients. A marked reduction in renal flow velocities was suggestive of proximal aortic stenosis in all 3 cases. We conclude that the diagnosis of aortic coarctation, an uncommon but not so rare form of secondary hypertension, by renal ultrasonography rather than by a complete physical examination, reflects a commitment failure of physicians in everyday management of hypertension.
BACKGROUND AND PURPOSE: The Plaque Hypertension Lipid-Lowering Italian Study (PHYLLIS) tested whether (1) the angiotensin-converting enzyme (ACE) inhibitor fosinopril (20 mg per day) was more effective on carotid atherosclerosis progression than the diuretic hydrochlorothiazide (25 mg per day), (2) pravastatin (40 mg per day) was more effective than placebo when added to either hydrochlorothiazide or fosinopril, and (3) there were additive effects of ACE inhibitor and lipid-lowering therapies. METHODS: A total of 508 hypertensive, hypercholesterolemic patients with asymptomatic carotid atherosclerosis were randomized to: (A) hydrochlorothiazide; (B) fosinopril; (C) hydrochlorothiazide plus pravastatin; and (D) fosinopril plus pravastatin, and followed up blindly for 2.6 years. B-Mode carotid scans were performed yearly by certified sonographers in 13 hospitals and read centrally. Corrections for drift were calculated from readings repeated at study end. Primary outcome was change in mean maximum intima-media thickness of far and near walls of common carotids and bifurcations bilaterally (CBM(max)). RESULTS: CBM(max) significantly progressed (0.010+/-0.004 mm per year; P=0.01) in group A (hydrochlorothiazide alone) but not in groups B, C, and D. CBM(max) changes in groups B, C, and D were significantly different from changes in group A. Changes in group A were concentrated at the bifurcations. "Clinic" and "ambulatory" blood pressure reductions were not significantly different between groups, but total and low-density lipoprotein cholesterol decreased by approximately 1 mmol/L in groups C and D. CONCLUSIONS: Progression of carotid atherosclerosis occurred with hydrochlorothiazide but not with fosinopril. Progression could also be avoided by associating pravastatin with hydrochlorothiazide.
OBJECTIVES: The aim of this study was to test the hypothesis that the angiotensin II type 1 receptor blocker (ARB) candesartan can reduce the risk of stroke in elderly patients with isolated systolic hypertension (ISH). BACKGROUND: Isolated systolic hypertension is the predominant form of hypertension in the elderly, and stroke is the most common cardiovascular (CV) complication. METHODS: In the Study on Cognition and Prognosis in the Elderly (SCOPE), 4,964 patients age 70 to 89 years were randomly assigned to double-blind candesartan or placebo with open-label antihypertensive therapy (mostly thiazide diuretics) added as needed to control blood pressure. Of the 4,964 patients, 1,518 had ISH (systolic blood pressure >160 mm Hg and diastolic blood pressure <90 mm Hg). The present study is a predefined subgroup analysis of outcome results in the ISH patients. RESULTS: Of the ISH patients, 754 were randomized to the candesartan group and 764 to the control group. Over the study period, blood pressure was reduced by 22/6 mm Hg in the candesartan group and by 20/5 mm Hg in the control group (difference between treatments 2/1 mm Hg; p = 0.101 and 0.064). A total of 20 fatal/non-fatal strokes occurred in the candesartan group (7.2/1,000 patient-years) and 35 in the control group (12.5/1,000 patient-years); relative risk (RR) was 0.58 (95% confidence interval 0.33 to 1.00), that is, a RR reduction of 42% (p = 0.050 unadjusted, p = 0.049 adjusted for baseline risk). There were no marked or statistically significant differences between the treatment groups in other CV end points or all-cause mortality. CONCLUSIONS: In elderly patients with ISH, antihypertensive treatment based on the ARB candesartan resulted in a significant 42% RR reduction in stroke in comparison with other antihypertensive treatment, despite little difference in blood pressure reduction.
BACKGROUND: In hypertensive left ventricular hypertrophy (LVH), myocardial texture is altered by a disproportionate increase in fibrosis, but there is insufficient clinical evidence whether antihypertensive therapy or individual agents can induce regression of myocardial fibrosis. METHODS AND RESULTS: We compared the effects of an angiotensin II receptor antagonist with a beta-blocker on myocardial collagen volume (assessed by echoreflectivity and serum collagen markers) in 219 hypertensive patients with echocardiographically documented LVH. Patients were allocated randomly to receive losartan 50 to 100 mg/d (n=111) or atenolol 50 to 100 mg/d (n=99) with or without hydrochlorothiazide 12.5 to 25 mg/d for 36 weeks. Echoreflectivity analysis was conducted on ultrasound tracings of the midapex septum with specifically designed and validated software. A color histogram of reflecting echoes was obtained, and its spread (broadband [BB], previously shown to correlate directly with collagen volume fraction on endomyocardial biopsies) was used as the primary outcome measure. Mean color scale and serum markers of collagen synthesis (PIP, PIIIP) or degradation (CITP) were secondary outcome variables. Echoreflectivity analysis proved feasible in 106 patients (losartan 52, atenolol 54). Losartan reduced BB over 36 weeks (from 114.5 to 104.3 color levels, P<0.02), whereas atenolol treatment was associated with an increase in BB (from 109.0 to 113.6 color levels, P=NS), the difference between treatments being -12.8 color levels (95% CI -23.6 to -2.0, P=0.02). Secondary end points (mean color scale and collagen markers) also changed in the direction of decreased collagen in patients receiving losartan, but differences between groups were not statistically significant. CONCLUSIONS: In hypertensive patients with LVH, losartan decreases myocardial collagen content, whereas atenolol does not. The difference between the 2 treatments is statistically significant.
BACKGROUND: The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial was designed to test the hypothesis that for the same blood-pressure control, valsartan would reduce cardiac morbidity and mortality more than amlodipine in hypertensive patients at high cardiovascular risk. METHODS: 15?245 patients, aged 50 years or older with treated or untreated hypertension and high risk of cardiac events participated in a randomised, double-blind, parallel-group comparison of therapy based on valsartan or amlodipine. Duration of treatment was event-driven and the trial lasted until at least 1450 patients had reached a primary endpoint, defined as a composite of cardiac mortality and morbidity. Patients from 31 countries were followed up for a mean of 4.2 years. FINDINGS: Blood pressure was reduced by both treatments, but the effects of the amlodipine-based regimen were more pronounced, especially in the early period (blood pressure 4.0/2.1 mm Hg lower in amlodipine than valsartan group after 1 month; 1.5/1.3 mm Hg after 1 year; p<0.001 between groups). The primary composite endpoint occurred in 810 patients in the valsartan group (10.6%, 25.5 per 1000 patient-years) and 789 in the amlodipine group (10.4%, 24.7 per 1000 patient-years; hazard ratio 1.04, 95% CI 0.94-1.15, p=0.49). INTERPRETATION: The main outcome of cardiac disease did not differ between the treatment groups. Unequal reductions in blood pressure might account for differences between the groups in cause-specific outcomes. The findings emphasise the importance of prompt blood-pressure control in hypertensive patients at high cardiovascular risk.
The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial was designed to test whether, for the same achieved blood pressures, regimens based on valsartan or amlodipine would have differing effects on cardiovascular endpoints in high risk hypertension. But inequalities in blood pressure, favouring amlodipine, throughout the multiyear trial precluded comparison of outcomes. A technique of serial median matching, applied at 6 months when treatment adjustments intended to achieve control of blood pressure were complete, created 5006 valsartan-amlodipine patient pairs matched exactly for systolic blood pressure, age, sex, and the presence or absence of previous coronary disease, stroke, or diabetes. Subsequent combined cardiac events, myocardial infarction, stroke, and mortality were almost identical in the two cohorts, but admission to hospital for heart failure was significantly lower with valsartan. Reaching blood pressure control (systolic <140 mm Hg) by 6 months, independent of drug type, was associated with significant benefits for subsequent major outcomes; the blood pressure response after just 1 month of treatment predicted events and survival.
BACKGROUND: The clinical significance of stratifying cardiovascular risk in hypertensive patients on the basis of retinal changes such as arteriolar narrowing or arterio-venous crossing has been criticized. AIM: Objectives of the study were: (i) to compare the prevalence of retinal abnormalities detected by non-mydriatic retinography with that of other quantitative markers of target organ damage (TOD), such as echocardiographically determined left ventricular hypertrophy (LVH), carotid structural abnormalities and microalbuminuria in recently diagnosed and never treated hypertensives; (ii) to assess the inter- and intra-observer reproducibility in evaluating retinal microvascular changes. METHODS: One hundred ninety-seven grade 1 (73%) and grade 2 essential hypertensives (119 males; mean age 46.8 +/- 12.0 years, duration of hypertension: 2.3 +/- 1.8 years) referred for the first time to our outpatient hypertension hospital clinic were subjected to the following procedures: (i) repeated clinic blood pressure (BP) measurements; (ii) electrocardiogram; (iii) routine blood chemistry and urinalysis; (iv) 24-h urine collection for microalbuminuria; (v) 24-h ambulatory BP monitoring; (vi) non-mydriatic retinography; (vii) echocardiogram; (viii) carotid ultrasonography. Retinal changes were evaluated according to a modified Keith, Wagener and Barker (KWB) classification by two physicians, who had no knowledge of the patients' characteristics. These following markers of TOD were considered: (i) left ventricular mass index > or = 125 g/m2 in men and > or = 110 g/m2 in women; (ii) at least one carotid plaque (focal thickening > 1.3 mm) or diffuse common carotid thickening (> or = 0.9 mm); (iii) microalbuminuria (urinary albumin excretion > or = 30 and < 300 mg/24 h). RESULTS: The prevalence rates of LVH, carotid structural alterations and microalbuminuria were 12.9, 26.0 and 8.6% respectively; while the distribution of patients in the different degrees of hypertensive retinopathy made by two independent readers (1 and 2) was: 0 = 15.2, I = 25.4, II = 58.9, III = 0.5% (1); 0 = 14.7, I = 27.9, II = 56.8, III = 0.5% (2), p = NS. The overall prevalence of retinal changes was 84.3% and 84.7%, respectively, and the inter- and intra-observer reproducibility 89.1, 91.6 (1) and 90.2% (2), respectively. CONCLUSIONS: Our data indicate that: (i) the prevalence of initial retinal changes is far higher than that of other prognostically validated quantitative markers of cardiac and extracardiac TOD; (ii) the inter- and intra-observer reproducibility between two skilled readers in detecting these abnormalities with non-mydriatic retinography is excellent; (iii) the high prevalence of retinal changes in untreated subjects with mild hypertension offers a new piece of evidence that they cannot be considered a proof of TOD.
OBJECTIVE: The aim of this study was to examine whether an impaired reduction in nocturnal blood pressure (BP), defined on the basis of two periods of ambulatory BP monitoring (ABPM), is present in hypertensive patients with metabolic syndrome, as defined by the NCEP criteria. METHODS: 460 grade 1 and 2 untreated essential hypertensives (mean age 45.9 +/- 11.9 years) referred for the first time to our outpatient hospital clinic underwent the following procedures: 1) medical history and physical examination; 2) repeated clinic BP measurements; 3) routine examinations; 4) ABPM over two 24-hour periods within 4 weeks. Metabolic syndrome was defined as at least three of the following alterations: increased waist circumference, increased triglycerides, decreased HDL-cholesterol, increased BP, or high fasting glucose. Nocturnal dipping was defined as a night-time reduction in average SBP and DBP >10% compared to average daytime values. RESULTS: The 135 patients with metabolic syndrome (group I) were similar for age, gender and known duration of hypertension to the 325 patients without it (group II). There were no significant differences between the two groups in average 48-hour, daytime, night-time SBP/DBP values and the percentage nocturnal SBP and DBP decrease (-17.7 / -15.7 vs. -18.4 / -16.2, p = ns). A reproducible nocturnal dipping (decrease in BP >10% from mean daytime in both ABPM periods) and non-dipping profile (decrease in BP < or =10% in both ABPM periods) was found in 74 (54.8%) and 29 (21.4%) in group I and in 169 (52.1%) and 73 (22.4%) in group II, respectively (p = ns); 32 patients (23.7%) in group I and 83 patients (25.5%) in group II had a variable dipping profile (p = ns). CONCLUSIONS: This study shows that no significant difference exists in nocturnal BP patterns, assessed by two ABPMs, in untreated essential hypertensive patients with metabolic syndrome compared to those without it.
BACKGROUND: The 2003 European Society of Hypertension/European Society of Cardiology (ESH-ESC) guidelines have recently proposed a new risk stratification scheme for estimating absolute risk for cardiovascular disease. At variance from the previous 1999 World Health Organization-International Society of Hypertension (WHO/ISH) guidelines, the new criteria include some additional risk factors such as obesity, abnormal high-density (HDL) or low-density lipoprotein (LDL) cholesterol levels and define a slight increase in creatinine and microalbuminuria as signs of target organ damage (TOD). OBJECTIVE: The aim of the study was to assess overall cardiovascular risk in uncomplicated hypertensives according to the 2003 ESH-ESC guidelines comparing this approach with the stratification scheme of the 1999 WHO/ISH guidelines. METHODS: Four hundred and twenty-five never-treated grade 1 and 2 essential hypertensive patients, referred for the first time to our outpatient clinic without diabetes mellitus, were included in the study. They underwent the following procedures: (i) repeated clinical blood pressure measurements; (ii) routine blood chemistry and urine analysis; (iii) electrocardiogram; (iv) 24-h urine collection for microalbuminuria; (v) echocardiogram; and (vi) carotid ultrasonogram. Risk was assessed according to both stratification schemes suggested by the 2003 ESH-ESC and 1999 WHO/ISH guidelines. RESULTS: According to the 2003 ESH-ESC guidelines, 15.5% of the 425 patients were considered at low added risk, 47.8% at medium added risk and 36.7% at high added risk; 146 patients (34.3%) were classified in the high-risk stratum because of at least one manifestation of TOD and 5.6% having three or more risk factors. The accuracy in detecting TOD of the combined approach with ultrasound procedures and microalbuminuria was approximately 10-fold higher than that provided by routine investigation. As a result of the 1999 WHO/ISH stratification scheme, 34.5% were low-risk, 34.4% medium-risk and 31.1% high-risk patients. CONCLUSIONS: Our findings show that: (i) more than one-third of uncomplicated grade 1 and 2 hypertensives seen in a outpatient hypertension hospital clinic have a high added risk according to the ESH-ESC scheme; (ii) classification of the patients in the high stratum is mainly influenced by the presence of TOD; (iii) the routine diagnostic work-up is a highly insensitive approach for the detection of TOD; (iv) the 2003 ESH-ESC guidelines stratify a higher proportion of hypertensive patients in the medium and high-risk groups than do the 1999 WHO/ISH guidelines.
New evidence from recently completed clinical studies performed with nebivolol, a highly selective beta-1 beta-blocker, endowed with additional vasodilating activity mediated by nitric oxide (NO) endothelial release, confirm previous findings that nebivolol differs from other beta-blocking agents and that the combination of beta-1 blockade and NO-mediated vasodilation not only potentiates the blood pressure lowering activity, but leads to a broader favourable haemodynamic profile, which is clinically relevant to the treatment of hypertensive patients. In particular, six new studies focusing on the vasodilation properties of nebivolol demonstrated that: (i) its blood pressure lowering effect is accompanied by a vasodilating action that is seen after single and chronic administration of the usual antihypertensive oral dose of 5 mg once daily; (ii) the vasodilation can be documented systemically, at various regional vascular beds and skin microcirculation, and is accompanied by increased small arterial distensibility; (iii) the NO-endothelium-dependency of its vasodilating action is shown by the model of forearm or cutaneous vasodilating response to acetylcholine and by the blockade of the nebivolol-induced local vasodilation by a blocker of the arginine-NO cascade, L-NMMA. Two more studies demonstrated the ability of nebivolol to increase NO concentrations through preservation of NO from oxidative degradation, and not only by stimulation of its synthesis. Finally, two studies confirmed the favourable haemodynamic action of nebivolol on both systolic and diastolic function and, in particular, an increase in stroke volume, associated with reduction in vascular resistance, resulting in a maintained cardiac output despite reduced heart rate. These properties consistently differentiate nebivolol from non-vasodilating beta-blockers, such as those used for the active comparative studies, i.e. atenolol, metoprolol or bisoprolol. The observation that nebivolol enhances or restores NO-mediated vasodilation in hypertensive patients has important therapeutic implications in view of the well-established protective role of NO against cardiovascular risk factors, and particularly the development of atherosclerosis. Similarly, the favourable haemodynamic profile of nebivolol, as described by the new investigations (preservation of cardiac output, reduction of peripheral resistance and improved diastolic function) appear to have clinically relevant benefits on the impairment in systolic and/or diastolic function often complicating the hypertension.
OBJECTIVE: The clinical significance of classifying patients as dippers and non-dippers on the basis of a single period of ambulatory blood pressure monitoring (ABPM) has been questioned. The aim of this study was to evaluate the relationship between nocturnal dipping status, defined on the basis of two periods of ABPM, and cardiac and extracardiac target organ damage in essential hypertension. METHODS: A total of 375 never-treated essential hypertensive patients [mean 24-h blood pressure (BP) > or = 125/80 mmHg; mean +/- SD age 45.9 +/- 11.9 years] referred for the first time to our outpatient clinic underwent the following procedures: (i) repeated clinic BP measurements; (ii) blood sampling for routine chemistry examinations; (iii) 24-h urine collection for microalbuminuria; (iv) ABPM over two 24-h periods within 4 weeks; (v) echocardiography; and (vi) carotid ultrasonography. RESULTS: A reproducible nocturnal dipping (decrease in BP > 10% from mean daytime BP in both ABPM periods) and non-dipping profile (decrease in BP < or = 10% in both ABPM periods) was found in 199 (group I) and 79 patients (group II), respectively; 97 patients (group III) had a variable dipping profile. The three groups did not differ with regard to age, gender, body mass index, clinic BP, 48-h BP and heart rate. Left ventricular mass index, interventricular septum thickness, left atrium and aortic root diameters were significantly higher in group II compared with group I (mean +/- SD 108.5 +/- 19.5 versus 99.7 +/- 19.6 g/m, P < 0.05; 9.3 +/- 0.9 versus 9.1 +/- 0.9 mm, P < 0.05; 33.6 +/- 3.6 versus 32.2 +/- 3.7 mm, P < 0.01; 36.9 +/- 4.6 mm versus 35.5 +/- 4.6, P < 0.05, respectively). The smaller differences seen between groups II and III and between groups I and III were not statistically significant. The prevalence of left ventricular hypertrophy (defined as a left ventricular mass index > 134 g/m in men and > 110 g/m in women) was greater in group II (19%) than in group I (6%) (P < 0.05), whereas the differences between groups II and III and between groups I and III did not reach statistical significance. Differences among the three groups in the prevalence of carotid structural alterations (such as carotid plaques or intima-media thickening) were not statistically significant, and microalbuminuria had a similar prevalence in all three groups. CONCLUSIONS: Despite similar clinic and 48-h BP values, never-treated hypertensive patients with a persistent non-dipper pattern showed a significantly greater extent of cardiac structural alterations compared with subjects with a reproducible dipping pattern, but not those with a variable BP nocturnal profile. A non-dipping pattern diagnosed on two concordant ABPM periods instead of a single monitoring therefore represents a clinical trait associated with more pronounced cardiac abnormalities. Finally, in non-dipping middle-aged hypertensives, echocardiography appears to provide a more accurate risk stratification than carotid ultrasonography or microalbuminuria.
BACKGROUND: To assess the impact of immediate versus delayed antihypertensive treatment on the outcome of older patients with isolated systolic hypertension, we extended the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial by an open-label follow-up study lasting 4 years. METHODS: The Syst-Eur trial included 4695 randomized patients with minimum age of 60 years and an untreated blood pressure of 160-219 mmHg systolic and below 95 mmHg diastolic. The double-blind trial ended after a median follow-up of 2.0 years (range 1-97 months). Of 4409 patients still alive, 3517 received open-label treatment consisting of nitrendipine (10-40 mg daily) with the possible addition of enalapril (5-20 mg daily), hydrochlorothiazide (12.5-25 mg daily), or both add-on drugs. Non-participants (n = 892) were also followed up. RESULTS: Median follow-up increased to 6.1 years. Systolic pressure decreased to below 150 mmHg (target level) in 2628 participants (75.0%). During the 4-year open-label follow-up, stroke and cardiovascular complications occurred at similar frequencies in patients formerly randomized to placebo and those continuing active treatment. These rates were similar to those previously observed in the active-treatment group during the double-blind trial. Considering the total follow-up of 4695 randomized patients, immediate compared with delayed antihypertensive treatment reduced the occurrence of stroke and cardiovascular complications by 28% (P = 0.01) and 15% (P = 0.03), respectively, with a similar tendency for total mortality (13%, P = 0.09). In 492 diabetic patients, the corresponding estimates of long-term benefit (P < 0.02) were 60, 51 and 38%, respectively. CONCLUSIONS: Antihypertensive treatment can achieve blood pressure control in most older patients with isolated systolic hypertension. Immediate compared with delayed treatment prevented 17 strokes or 25 major cardiovascular events per 1000 patients followed up for 6 years. These findings underscore the necessity of early treatment of isolated systolic hypertension.
BACKGROUND: In ELSA, a randomized, double-blind trial in 2334 hypertensives, 4-year antihypertensive treatment with lacidipine slowed down progression of carotid atherosclerosis significantly more than atenolol treatment. To avoid bias, the primary outcome was measured blindly at study-end on a randomized sequence of scans, but measurements were limited to the four far walls of common carotids and bifurcations (CBMmax) and to one of each couple of duplicate scans recorded yearly. OBJECTIVES AND METHODS: Secondary outcomes included measurements made on all duplicate scans of both near and far walls, not only of common carotids and bifurcations, but also of internal carotids (12 walls). These measurements were made blindly during the 4-year study, shortly after recording. To avoid possible readers' drift or bias, 250 duplicate baseline scans were re-read at yearly intervals (longitudinal on-line quality control) and a correction factor calculated. RESULTS: Measurements during the 4-year study showed a trend toward decreased values, with the lacidipine effect significantly greater than the atenolol one. A trend toward lower values was also observed in the longitudinal quality control of baseline scans. After applying a correction factor calculated from this longitudinal control, all measurements no longer decreased with time, but significantly increased, with progression being significantly smaller in lacidipine than in atenolol patients. Corrected values were quite similar to those calculated on measurements carried out at study-end. CONCLUSION: The relative benefit of lacidipine over atenolol could be measured precisely by reading scans either during the study or at study-end. However, absolute treatment-related changes (progression versus regression) cannot safely be judged by readings made during a long-term study, unless a longitudinal quality control of readings is performed.
Microalbuminuria has been shown to predict an increased probability of suffering a cardiovascular event or death. It has also been shown to be decreased by antihypertensive therapy and in particular by drugs counteracting the effects of angiotensin II. In this issue of Journal of Hypertension data, from the LIFE study, are reported indicating for the first time that a decrease in urinary albumin excretion rate is accompanied by a significant decrease in cardiovascular events. This evidence is of great relevance because it constitutes the first evidence showing that regression of an intermediate end-point, microalbuminuria, ensures a better cardiovascular prognosis.
BACKGROUND: The prevalence and the relationship between metabolic syndrome, and target organ damage (TOD) in essential hypertensive patients has not been fully explored to date. OBJECTIVE: To investigate the association between metabolic syndrome, as defined by the ATP III report, and cardiac and extracardiac TOD, as defined by the 2003 ESH-ESC guidelines for management of hypertension, in a large population of never-treated essential hypertensives. METHODS: A total of 447 grade 1 and 2 hypertensive patients (mean age 46 +/- 12 years) who were attending a hypertension hospital outpatient clinic for the first time underwent the following procedures: (i) physical examination and repeated clinic blood pressure measurements; (ii) routine examinations; (iii) 24-h urine collection for microalbuminuria; (iv) 24-h ambulatory blood pressure monitoring; (v) echocardiography; and (vi) carotid ultrasonography. Metabolic syndrome was defined as involving at least three of the following alterations: increased waist circumference, increased triglycerides, decreased high-density lipoprotein cholesterol, increased blood pressure, or high fasting glucose. Left ventricular hypertrophy (LVH) was defined according to two different criteria: (i) 125 g/m in men and 110 g/m in women; (ii) 51 g/h in men and 47 g/h in women. RESULTS: The 135 patients with metabolic syndrome (group I) were similar for age, sex distribution, known duration of hypertension and average 24-h, daytime and night-time ambulatory blood pressure to the 312 patients without it (group II). The prevalence of altered left ventricular patterns (LVH and left ventricular concentric remodelling) was significantly higher in group I (criterion a = 30%, criterion b = 42%) than in group II (criterion a = 23%, criterion b = 30%, P < 0.05 and P < 0.01, respectively). A greater urinary albumin excretion (17 +/- 35 versus 11 +/- 23 mg/24 h, P = 0.04) was also found in group I compared to group II. There were no significant differences between the two groups in the prevalence of carotid intima-media thickening and plaques. CONCLUSIONS: These results from a representative sample of untreated middle-aged hypertensives show that: (i) the metabolic syndrome is highly prevalent in this setting and (ii) despite similar ambulatory blood pressure values, patients with metabolic syndrome have a more pronounced cardiac and extracardiac involvement than those without it.
BACKGROUND AND PURPOSE: The clinical and prognostic significance of initial retinal alterations in hypertensive patients remains controversial. Therefore, we assessed the relationship of microvascular abnormalities with prognostically validated markers of target organ damage (TOD), such as left ventricular mass (LVM), carotid intima-media thickness (IMT) and microalbuminuria, in early stages of untreated essential hypertension. METHODS: A total of 437 consecutive, never-treated patients with grade 1 or 2 essential hypertension, referred to our outpatient clinic, underwent the following procedures: (1) clinical and routine laboratory examinations, (2) 24-h ambulatory blood pressure monitoring, (3) 24-h urine collection for microalbuminuria, (4) echocardiography, (5) carotid ultrasonography, (6) non-mydriatic retinography. Patients were divided into group I, with either a normal retinal pattern (n=65, 14.9%) or arteriolar narrowing (n=185, 42.4%) and group II with arteriovenous crossings (n=187, 42.7%). RESULTS: The two groups were similar for gender, body mass index, smoking habit, heart rate, clinic and ambulatory blood pressure (BP) values, while mean age was slightly but significantly higher in group II than in group I (47.6 +/- 10.7 versus 44.5 +/- 12.5 years, P=0.008). No differences occurred between the two groups in LVM index (101.8 +/- 18.5 versus 99.9 +/- 20.4 g/m), carotid IMT (0.67 +/- 0.12 versus 0.66 +/- 0.20 mm), urinary albumin excretion rate (14.4 +/- 27.7 versus 13.3 +/- 27.7 mg/24 h) as well as in the prevalence of LV hypertrophy (14.3 versus 14.0%), IM thickening and/or plaques (26.5 versus 27.2%) (both defined according to 2003 ESH-ESC guidelines) and microalbuminuria (10.1 versus 8.7%). Furthermore, the three different retinal artery patterns were similarly distributed among tertiles of LV mass index, IMT and urinary albumin excretion rate. CONCLUSIONS: These results show that: (1) a very large fraction (more than 80%) of untreated, recently diagnosed hypertensive patients have initial retinal microvascular abnormalities detectable by non-mydriatic retinography, (2) the presence of arteriovenous crossings is not associated with more prominent cardiac and extracardiac TOD, (3) fundoscopic examination has a limited clinical value to detect widespread organ involvement in early phases of grade 1 and 2 hypertension.
Diabetes mellitus and hypertension, responsible of a major burden of cardiovascular complications, are increasing their incidence in Latin America in similar proportions to the rest of the world. The metabolic syndrome, a strong predictor of both diabetes and hypertension deserves more attention from the primary care physicians. Evidence based and updated guidelines on detection, prevention and treatment of diabetes and hypertension, issued by local experts, are willing to inform and translate these recommendations to the clinical practice of physicians assisting these patients throughout Latin America.