Retinal microvascular changes and target organ damage in untreated essential hypertensives.

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.

Cardiovascular risk stratification according to the 2003 ESH-ESC guidelines in uncomplicated patients with essential hypertension: comparison with the 1999 WHO/ISH guidelines criteria.

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.

High prevalence of retinal vascular changes in never-treated essential hypertensives: an inter- and intra-observer reproducibility study with non-mydriatic retinography.

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.

Cardiovascular target organ damage in essential hypertensives with or without reproducible nocturnal fall in blood pressure.

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.

Left ventricular hypertrophy in treated hypertensive patients with good blood pressure control outside the clinic, but poor clinic blood pressure control.

OBJECTIVE: The aim of the study was to evaluate the prevalence of left ventricular hypertrophy (LVH) in treated patients with good blood pressure (BP) control during multiple home BP (HBP) measurements and during 24-h ambulatory BP monitoring (ABPM), but with unsatisfactory BP control in the clinic. These patients were compared with treated hypertensives whose BP was well controlled under the three circumstances. METHODS: Seventy-two treated consecutive patients (group I, age 56 +/- 10 years) with clinic BP values > or = 140/90 mmHg, and a difference between clinic and self-measured HBP > 10 mmHg for diastolic blood pressure (DBP) and/or > 20 mmHg for systolic blood pressure (SBP), underwent the following procedures: (1) clinic BP measurement; (2) routine diagnostic work-up; (3) HBP monitoring; (4) 24-h ABPM; (5) echocardiography. Thirty-five hypertensive patients with satisfactory BP control according to clinic (< 140/90 mmHg), HBP (< or = 131/82 mmHg) and ABP criteria (< or = 125/79 mmHg) were included as the control group (group II, age 55 +/- 9 years). RESULTS: In group I, 33 subjects out of the 72 (46%) with clinic BP > 140/90 mmHg had BP values controlled outside the clinic (23 according to HBP criteria and 22 according to ABP criteria). The prevalence of LVH (LV mass index > 134 g/m2 in men and > 110 g/m2 in women) was significantly higher in these patients (15.1 versus 2.8%, P < 0.01) than in group II (BP also controlled in the clinic), despite the fact that HBP and ABP were reduced to similar levels in the two groups. CONCLUSIONS Our data provide evidence that treated hypertensive patients with good BP control at home or during ambulatory monitoring, but incomplete BP control in the clinic, have more pronounced cardiac alterations than patients with both clinic and out of the clinic BP control. This finding offers a new piece of information about the diagnostic value of BP measurement in the clinic to assess BP control during antihypertensive treatment.

Impact of carotid intima-media thickening on risk stratification in elderly hypertensives.

BACKGROUND: It has been shown that aging and arterial hypertension are both associated with an increased prevalence of carotid structural abnormalities, such as intima-media (IM) thickening or plaques, which are a powerful independent predictor of cardiovascular (CV) events. We investigated the impact of carotid IM thickening in profiling the absolute CV risk stratification according the 1999 World Health Organization/International Society of Hypertension (WHO/ISH) guidelines in elderly hypertensive patients. METHODS: Two hundred and thirty untreated elderly patients (>65 years) referred to our outpatient hospital clinic were included in the study. They underwent the following procedures: (i) medical history, physical examination and clinic blood pressure measurement; (ii) routine blood chemistry and urine analysis; (iii) electrocardiogram. The risk was initially stratified according to the routine procedures indicated by WHO/ISH guidelines and subsequently reassessed by adding the results of carotid ultrasonography (IM thickening as diffuse IM thickness >0.9 and <1.3 mm). RESULTS: According to routine classification 56% (=129) were medium-risk patients, 29% (n = 67) high-risk and 15% (n = 34) very-high-risk patients. The overall prevalence of carotid IM thickening was 54% (49% in medium-risk vs 60% in high or very high-risk patients, p < 0.05). A marked change in risk stratification was observed when IM thickening was taken in consideration: medium-risk patients decreased to 29% and high-risk rose to 56% (p < 0.01). CONCLUSIONS: Ultrasound assessment of large artery damage is extremely useful for a more accurate estimate of global CV risk in elderly hypertensives, because stratification based on diagnostic routine procedures can underestimate the overall risk in a large fraction of medium-risk subjects.

Trends in hypertension control and left ventricular hypertrophy over three years.

BACKGROUND: The aim of this study was to describe trends in blood pressure (BP) control and in the prevalence of left ventricular hypertrophy (LVH) during 3 years of follow-up in a representative sample of treated hypertensive patients seen in our out-patient hypertension hospital clinic. METHODS: Four hundred and sixty-four hypertensive treated patients who took part in a clinical survey at our out-patient clinic during the year 1997 and who had been submitted to a routine follow-up visit 3 years later were included in the study. All patients were subjected to the following procedures: an accurate medical history, physical examination, electrocardiogram, clinical BP measurement. For the diagnosis of LVH we used two different ECG criteria: the Solokow-Lyon voltage and the gender-specific Cornell voltage. RESULTS: During the first survey, 15% of treated patients had a clinical BP < 130/85 mmHg, 25.1% > or = 130/85 mmHg and < 140/90 mmHg, 33.6% > or = 140/90 and < 150/95 mmHg, 26.3% > or = 150/95 mmHg. The corresponding figures in the second survey were 19, 26.7, 33.2 and 21.1%, respectively. Overall, from the first to the second survey the prevalence of an effective BP control (< 140/90 mmHg) rose from 40.1 to 46.7% (p < 0.01). At baseline, 40 patients had ECG LVH (8.6%); at the second visit, LVH was found to have regressed in 19 of these patients. Among the 424 patients with a normal baseline electrocardiogram, 3 developed LVH during follow-up. Hence, the prevalence of LVH decreased from 8.6 to 5.1% (p < 0.01). In terms of treatment, the prevalence of combination therapy regimens increased from 68.6 to 79.7% (p < 0.05). CONCLUSIONS: This study demonstrates that in hypertensive patients managed in a hypertension hospital clinic, BP control improved during the long-term follow-up and that this trend was associated with a significant regression in ECG LVH.