Prevalence and incidence of the metabolic syndrome in the European Lacidipine Study on Atherosclerosis (ELSA) and its relation with carotid intima-media thickness

BACKGROUND: The European Lacidipine Study on Atherosclerosis (ELSA) randomized 2334 hypertensive patients to either the lipophilic calcium antagonist lacidipine or the beta-blocker atenolol for 4 years. About 35% of subjects in both groups received additional hydrochlorothiazide (12.5-25 mg/day). The patients were followed up for carotid intima-media thickness (IMT) changes for 3.7 years. OBJECTIVES: The present post-hoc analyses were aimed at: describing the prevalence of the metabolic syndrome (MS) at baseline; investigating the effect of long-term antihypertensive therapy (and separately of atenolol and lacidipine) on MS prevalence; exploring whether MS at baseline influenced changes in carotid IMT and incidence of cardiovascular events during treatment; and describing the relations between MS and new cases of diabetes developing during treatment. METHODS: At baseline 2034 patients had, in addition to blood pressure (BP), measurements of blood glucose, serum high-density lipoprotein (HDL)-cholesterol, triglycerides and body mass index (BMI > 28.8 for men and > 26.2 for women were taken to correspond to waist circumference > 102 and > 88 cm, respectively). These measurements were repeated after 4 years of treatment in 1444 patients. MS was defined according to Adults Treatment Panel III (ATP III). RESULTS: A high proportion of ELSA patients (33.3%) had MS at baseline, with no difference between atenolol and lacidipine. Baseline IMT was slightly greater in MS patients, but only the difference in mean maximum IMT at common carotids and bifurcations (CBMmax) achieved significance (P = 0.0325). Progression of CBMmax was also slightly greater in MS patients (P = 0.0241), but significance was lost when adjusted for covariates. No significant difference was found in the incidence of new cardiovascular events between patients with and without MS. The incidence of new MS was 21.4%, and significantly greater in patients under atenolol (25.2%) than lacidipine (17.7%; P = 0.0045). New-onset diabetes occurred in 5.54% of ELSA patients, and was three times higher among patients with than those without MS (10.28 versus 3.43%, P > 0.0001). CONCLUSIONS: Our analyses show a high prevalence of MS in ELSA hypertensives, a substantial incidence of new cases of MS and diabetes, the latter mostly among patients with MS. These analyses also show that in ELSA lacidipine was superior to atenolol, not only in showing a lower progression of carotid atherosclerosis, but also in causing a significantly lower incidence of new MS.     

Carotid wall composition in hypertensive patients after 4-year treatment with lacidipine or atenolol: an echoreflectivity study

OBJECTIVE: In the European Lacidipine Study on Atherosclerosis (ELSA), against a similar antihypertensive effect, a significantly greater effect of lacidipine was found on carotid intima-media thickness (IMT) progression, indicating a specific anti-atherosclerotic effect of lacidipine. However, not only the extent but also the composition of an atherosclerotic plaque is a determinant of subsequent events. DESIGN AND METHODS: Among the 2334 patients enrolled in ELSA, 420 with 4-year treatment were chosen, videodensitometric analysis of their ultrasound carotid scan was performed and the maximum wall lesion (Tmax) was classified as lipidic, fibrolipidic and fibrotic by means of software previously validated against histology. Of the 420 patients, 244 had scans suitable for videodensitometry. RESULTS: Excellent reproducibility of videodensitometry analysis was found using the Bland-Altman and other methods. At baseline, ELSA hypertensive patients had predominantly fibrolipidic walls (70%), with an echoreflectivity indicating a mean collagen content of 25%. After 4 years of antihypertensive treatment, little change in the frequency distribution of carotid lesions (fibrolipidic 73%) was found, with no significant differences between patients randomized to lacidipine or atenolol. CONCLUSIONS: Our study provides previously unavailable information that carotid wall composition changes to an extremely small extent during 4-year effective blood pressure lowering. With lacidipine, stable composition is associated with a lower IMT progression than with atenolol.     

The effect of lowered pressure on the diastolic ventricular function after antihypertensive treatment]

Thirty hypertensive patients with increased left ventricular (LV) mass and impaired diastolic function received routinely 2 or 3 kinds of captopril, nifedipine and atenolol for a mean period of 98 days. The LV mass index (LVMI) decreased by an average of 21 g/M2, but no significant correlation between blood pressure reduction and decrease in LVMI was found. So there may be some direct effect of these antihypertensive agents on the myocardium in addition to the benefit from blood pressure reduction. Marked reduction in PVA, Ai, A/E and Ai/T-VTi (P less than 0.01) along with elevation in ratio of E/A, Ei/Ai and Ei/T-VTi (P less than 0.01) were also observed by Doppler transmitral filling studies. These results indicated that the impaired LV diastolic function in patients with hypertension can be much improved following reduction of blood pressure and LV mass.     

Absolute and relative changes in carotid intima-media thickness and atherosclerotic plaques during long-term antihypertensive treatment: further results of the European Lacidipine Study on Atherosclerosis (ELSA)

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.     

动态脉压对老年高血压患者靶器官损害的影响

目的探讨动态脉压对老年高血压患者靶器官损害的影响。方法选择原发性高血压患者146例,按24 h平均脉压(MPP)分为2组:24 h MPP≥60 mm Hg(1 mm Hg=0.133 kPa)为A组(60例),24 h MPP<60 mm Hg为B组(86例);另选健康体检者为对照组(C组,30例)。所有患者均行血清肌酐、动态血压、超声心动图、颈动脉超声检查;计算肌酐清除率(Ccr)、24 h平均收缩压(MSBP)、24 h平均舒张压、24 h MPP、左心室重量指数(LVMI)、LVEF、颈动脉内膜中层厚度(IMT)。结果与C组比较,A组和B组患者24 h MSBP、24 h MPP、LVMI、IMT、左心室肥厚、左心室功能受损、脑损害、肾功能受损、颈动脉斑块发生率明显升高,Ccr、LVEF水平明显降低(P<0.05,P<0.01);与B组比较,A组患者Ccr、LVEF水平明显降低,24 h MSBP、24 h MPP、LVMI、IMT、靶器官损害发生率均明显升高(P<0.05,P<0.01)。24 h MPP与心脑肾和颈动脉损害相关(P<0.05)。结论动态脉压增大与老年高血压患者靶器官结构和功能的损害相关;动态脉压越大,靶器官损害越严重。     

Irbesartan reduces common carotid artery intima-media thickness in hypertensive patients when compared with atenolol: the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) study

BACKGROUND AND PURPOSE: Angiotensin II promotes cell growth and has been implicated in the development and maintenance of left ventricular (LV) hypertrophy and of structural vascular changes. We wished to examine whether an angiotensin receptor blocker (ARB) would influence structural vascular changes beyond the effects of blood pressure reduction. METHODS: Hypertensive patients with LV hypertrophy (age 55 +/- 9 years, blood pressure 162 +/- 19/104 +/- 8 mmHg, LV mass index 148 +/- 31 g m(-2); mean +/- SD) were randomized double-blind to the ARB irbesartan (n=52) or the beta(1) receptor blocker atenolol (n=56) for 48 weeks. Ultrasonography of the left and right common carotid artery (CCA) and echocardiography were performed at week 0 and 48. RESULTS: With similar reductions in blood pressure, CCA intima-media thickness (IMT) was reduced by irbesartan (from 0.92 +/- 0.14 by 0.01 +/- 0.10 mm, NS), whereas it was increased by atenolol (from 0.94 +/- 0.21 by 0.03 +/- 0.12 mm, P=0.018; P=0.002 between groups). CCA lumen diameter was less reduced by irbesartan than by atenolol. Thus, CCA intima-media area was reduced by irbesartan (from 21.3 +/- 5.0 by 0.90 +/- 2.45 mm(2), P=0.034) but not by atenolol (from 21.3 +/- 6.1 by 0.18 +/- 2.71 mm(2), NS; P=0.037 between groups). Changes in CCA IMT or area did not relate to changes in LV mass. CONCLUSIONS: The favourable effects by irbesartan on CCA IMT with an outward vascular remodelling suggest that angiotensin II mediates structural vascular changes, beyond the effects of blood pressure. This may be important in the prevention of cerebrovascular events.     

Importance of blood pressure control in left ventricular mass regression

Blood pressure (BP) reduction to 140/90 mm Hg or lower using renin-angiotensin-system blockers reportedly provides the greatest left ventricular (LV) mass regression; β-blockers have less effect. This study examined whether combination antihypertensive therapy would provide greater benefit. With a double-blind, parallel-group design, the effects of 3 different combinations, carvedilol controlled-release (CR)/lisinopril, atenolol/lisinopril, and lisinopril, on left ventricular mass index (LVMI) were assessed by MRI after 12 months. Patients were treated to achieve guideline-recommended BP (<140 mm Hg/<90 mm Hg; diabetes: <130 mm Hg/<80 mm Hg). Sample size was calculated to achieve 90% power to detect a 5 g/m² difference in mean change from baseline in LVMI between the carvedilol CR/lisinopril group and each of the other treatment groups. Of 287 patients randomized, more than 50% were titrated to maximum dosage; 73% reached targeted BP. At month 12 (last observation carried forward ≥ month 9) for 195 evaluable subjects, mean BP was similar in all groups (carvedilol CR/lisinopril: 128.8/77.9; atenolol/lisinopril: 128.7/76.5; lisinopril: 126.3/80.3 mm Hg). Compared with baseline, mean LVMI decreased to a similar extent in all groups (carvedilol CR/lisinopril: –6.3; atenolol/lisinopril: –6.7; lisinopril: –7.9 g/m²). Achievement of targeted BP control is more important than treatment regimen in achieving LV mass reduction.     

Does long-term losartan- vs atenolol-based antihypertensive treatment influence collagen markers differently in hypertensive patients? A LIFE substudy

BACKGROUND: The aim of this study was to investigate the effects of losartan- vs atenolol-based antihypertensive treatment on circulating collagen markers beyond the initial blood pressure (BP) reduction. METHODS: In 204 patients with hypertension and left ventricular (LV) hypertrophy we measured serum concentration of carboxy-terminal telopeptide of type I procollagen (ICTP), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), amino-terminal propeptide of type I procollagen (PINP) and LV mass by echocardiography at baseline and annually during 4 years of losartan- or atenolol-based antihypertensive treatment; 185 patients completed the study. RESULTS: Beyond the first year of treatment systolic and diastolic BP, LV mass index (LVMI) as well as collagen markers did not change significantly and were equal in the two treatment groups. Changes in PICP during first year of treatment were related to subsequent changes in LV mass index after 2 and 3 years of treatment (r=0.28 and r=0.29, both p<0.05) in patients randomized to losartan, but not atenolol. CONCLUSION: Long-term losartan- vs atenolol-based antihypertensive treatment did not influence collagen markers differently, making a BP-independent effect of losartan on collagen markers unlikely. However, initial reduction in circulating PICP may predict later regression of LV hypertrophy during losartan-based antihypertensive treatment.     

Markers of collagen synthesis is related to blood pressure and vascular hypertrophy: a LIFE substudy

Cardiac fibrosis and high levels of circulating collagen markers has been associated with left ventricular (LV) hypertrophy. However, the relationship to vascular hypertrophy and blood pressure (BP) load is unclear. In 204 patients with essential hypertension and electrocardiographic LV hypertrophy, we measured sitting BP, serum collagen type I carboxy-terminal telopeptide (ICTP) reflecting degradation, procollagen type I carboxy-terminal propeptide (PICP) reflecting synthesis and LV mass by echocardiography after 2 weeks of placebo treatment and after 1 year of antihypertensive treatment with a losartan- or an atenolol-based regimen. Furthermore, we measured intima-media thickness of the common carotid arteries (IMT), minimal forearm vascular resistance (MFVR) by plethysmography and ambulatory 24-h BP in around half of the patients. At baseline, PICP/ICTP was positively related to IMT (r=0.24, P<0.05), MFVR(men) (r=0.35, P<0.01), 24-h systolic BP (r=0.24, P<0.05) and 24-h diastolic BP (r=0.22, P<0.05), but not to LV mass. After 1 year of treatment with reduction in systolic BP (175+/-15 vs 151+/-17 mmHg, P<0.001) and diastolic BP (99+/-8 vs 88+/-9 mmHg, P<0.001), ICTP was unchanged (3.7+/-1.4 vs 3.8+/-1.4 microg/l, NS) while PICP (121+/-39 vs 102+/-29 microg/l, P<0.001) decreased. The reduction in PICP/ICTP was related to the reduction in sitting diastolic BP (r=0.31, P<0.01) and regression of IMT (r=0.37, P<0.05) in patients receiving atenolol and to reduction in heart rate in patients receiving losartan (r=0.30, P<0.01). In conclusion, collagen markers reflecting net synthesis of type I collagen were positively related to vascular hypertrophy and BP load, suggesting that collagen synthesis in the vascular wall is increased in relation to high haemodynamic load in a reversible manner.     

Transforming growth factor beta1 genotype and change in left ventricular mass during antihypertensive treatment--results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA)

BACKGROUND: Angiotensin II, via the angiotensin II type 1 (AT1) receptor, may mediate myocardial fibrosis and myocyte hypertrophy seen in hypertensive left ventricular (LV) hypertrophy through production of transforming growth factor beta1 (TGF-beta1); AT1-receptor antagonists reverse these changes. The TGF-beta1 G + 915C polymorphism is associated with interindividual variation in TGF-beta1 production. No study has yet determined the impact of this polymorphism on the response to antihypertensive treatment. HYPOTHESIS: We aimed to determine whether the TGF-beta1 G + 915C polymorphism was related to change in LV mass during antihypertensive treatment with either an AT1-receptor antagonists or a beta1-adrenoceptor blocker. The polymorphism was hypothesized to have an impact mainly on the irbesartan group. METHODS: We determined the association between the TGF-beta1 genotype and regression of LV mass in 90 patients with essential hypertension and echocardiographically diagnosed LV hypertrophy, randomized in a double-blind study to receive treatment for 48 weeks with either the AT1-receptor antagonist irbesartan or the beta1-adrenoceptor blocker atenolol. RESULTS: Irbesartan-treated patients who were carriers of the C-allele, which is associated with low expression of TGF-beta1, responded with a markedly greater decrease in LV mass index (LVMI) than subjects with the G/G genotype (adjusted mean change in LVMI -44.7 g/m2 vs. -22.2 g/m2, p = 0.007), independent of blood pressure reduction. No association between genotype and change in LVMI was observed in the atenolol group. CONCLUSIONS: The TGF-beta1 G + 915C polymorphism is related to the change in LVMI in response to antihypertensive treatment with the AT1-receptor antagonist irbesartan.     

Pulse pressure in normotensives: a marker of cardiovascular disease

The purpose of the present study was to evaluate the relation of the systemic arterial pulse pressure and other parameters derived from the 24-h arterial blood pressure (BP) monitoring to the severity of coronary artery disease, carotid lesions, and left ventricular (LV) mass index in patients without arterial hypertension. One hundred ten patients with known coronary artery disease underwent coronary arteriography, 24-h arterial BP monitoring, and ultrasound imaging of the carotid arteries and the myocardium. Measurements of 24-h arterial BP monitoring (systolic, diastolic, and average BP, pulse pressure, abnormal values of systolic and diastolic BP, and heart rate), the severity of coronary heart disease (Gensini score), intima-media thickness (IMT) of the common carotid artery and LV mass index were determined in all patients. By univariate analysis, only 24-h pulse pressure was significantly related to the severity of coronary artery disease (P < .01), carotid IMT(P < .01), and LV mass index (P < .01). In a multivariate analysis, 24-h pulse pressure was also the best predictor of the severity of coronary lesions (P = .009), carotid IMT (P = .003), and LV mass index (P = .009). Gensini score was related (P < .01) to LV mass index and not to carotid IMT. In conclusion, systemic arterial pulse pressure derived from 24-h arterial BP monitoring is related to coronary artery disease, carotid IMT, and LV mass index independently of age or any other derivative of 24-h arterial BP monitoring, indicating that this parameter could be a marker of global cardiovascular risk.     

Different relation between 24-h blood pressure and distensibility at different peripheral arteries. Data from the European Lacidipine Study on Atherosclerosis (ELSA)

INTRODUCTION: The European Lacidipine Study on Atherosclerosis (ELSA) has been planned to investigate the effect of reduction in office and ambulatory blood pressure by lacidipine versus atenolol on carotid artery wall thickness in mild to moderate essential hypertensive patients with no metabolic abnormalities. One prespecified sub-study of ELSA focused on measurements of arterial distensibility in the carotid as well as in the radial artery to determine the relationship of functional arterial properties with office versus ambulatory blood pressure (BP) values as well as the correspondence between functional and structural arterial alterations. METHODS: The sub-study was conducted on 124 patients recruited in four centres (Monza-Milan, Paris, Grenoble and Glasgow). BP was measured both by a mercury sphygmomanometer and by 24-h ambulatory monitoring. Common carotid artery wall thickness was measured by certified sonographers as described in the main study. Common carotid and radial artery distensibility were obtained by echotracking techniques, which allowed to relate changes in arterial diameter with systo-diastolic BP changes. RESULTS: Carotid artery wall distensibility showed (1) a negative correlation with office and more so 24-h average systolic BP (r = -0.45 and -0.58, P < 0.008 and 0.001) but not with office or 24-h diastolic BP) and (2) a negative correlation with the corresponding wall thickness (r = -0.47, P < 0.005). In contrast, at the radial artery level distensibility and thickness showed no correlation with each other and with BP. Carotid (but not radial) artery distensibility also correlated with ambulatory systolic BP variability but the correlation was lost after adjustment for age and mean BP values. CONCLUSION: These data suggest that stiffening of large elastic artery is reflected more by ambulatory than office BP elevations, systolic BP being much more important than diastolic. Alterations of large elastic arteries function is related to structural wall changes. Functional and structural properties of middle-size muscle arteries are independent of BP.     

Changes in midwall systolic performance and cardiac hypertrophy reduction in hypertensive patients

OBJECTIVE: To investigate changes in left ventricular (LV) performance, as evaluated by measurement of midwall LV fractional shortening (FS), after reduction of cardiac hypertrophy. DESIGN AND METHODS: Echocardiographic evaluation of LV anatomy and function was performed by M-mode echocardiography at baseline, after long-term antihypertensive therapy, and after treatment withdrawal in 68 asymptomatic hypertensive patients (50 males, 18 females, age range 22-62 years). Patients were divided according to the presence of LV hypertrophy (LVH) at baseline (LV mass index, LVMI, > or = 51 g/m(2.7)). RESULTS: At baseline patients with concentric (relative wall thickness > 0.44) LV hypertrophy (n = 38) or remodelling (n = 7) had reduced midwall shortening with respect to patients with normal LV geometry (n = 4) or eccentric LVH (n = 19); no differences were observed for endocardial FS. After long-term treatment (average 15 months), in 11 patients LV mass remained within normal limits, in 45 patients LVH reduction was obtained, while in 12 patients LV mass remained persistently elevated. Midwall FS was significantly increased in patients with reduction of LVH both during treatment and after withdrawal of treatment, while it remained significantly lower in patients with persistently elevated LV mass. Changes in midwall fractional shortening were independently associated with modifications in relative wall thickness (P < 0.00001), with changes in end-diastolic dimensions (P < 0.0001) and those of LVMI (P< 0.02) as shown by multivariate analysis. CONCLUSION: LV midwall systolic performance significantly improved after reduction of LVH, even in the presence of high blood pressure values. Modifications in relative wall thickness are more independently associated with changes, in LV diastolic dimensions and mass, to midwall improvement     

Baseline reproducibility of B-mode ultrasonic measurement of carotid artery intima-media thickness: the European Lacidipine Study on Atherosclerosis (ELSA)

BACKGROUND AND OBJECTIVE: The European Lacidipine Study of Atherosclerosis (ELSA) is a prospective, randomized, double-blind, multi-national interventional trial to determine the effect of four-year treatment using the calcium antagonist lacidipine versus the beta-blocker atenolol on the progression of carotid atherosclerosis in 2259 asymptomatic hypertensive patients. B-mode ultrasound is used to measure the primary and secondary endpoints including the mean maximum intima-media thickness (IMT) of the carotid bifurcations and the common carotid arteries (CBM(max)), the mean maximum IMT of 12 standard carotid sites (M(max)) and the overall maximum IMT (T(max)). This paper reports the cross-sectional reproducibility of ultrasound measurements at baseline. METHOD: To evaluate measurement reliability, each patient is scanned twice at baseline and again at four annual visits, with 80% of the replicate scans performed by the same sonographer and 20% by a different sonographer; 50% of the replicate scans are read by the same reader and the other 50% by different readers. RESULTS: The overall coefficient of reliability (R) was 0.859 for CBM(max), 0.872 for M(max) and 0.794 for T(max). The reliability for CBM(max) was stable during the 1 3/4-year baseline period (R = 0.848 to 0.953) and was uniform among the 23 field centres (R = 0.798 to 0.926). Intra- and inter-reader reliability were 0.915 and 0.872 respectively, and intra-sonographer reliability was 0.866. CONCLUSION: The results demonstrate that by implementing standardized protocols and strict quality control procedures, highly reliable ultrasonic measurements of carotid artery IMT can be achieved in large multi-national trials.     

Impact of age on left ventricular hypertrophy regression during antihypertensive treatment with losartan or atenolol (the LIFE study)

To assess the influence of age on changes in left ventricular (LV) mass and geometry during antihypertensive treatment, we related age to clinical and echocardiographic findings before and after 4 years of antihypertensive treatment in a subset of 560 hypertensive patients without known concurrent disease in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, which randomized patients to blinded losartan- or atenolol-based treatment. Patients >/=65 years (older group) included more women and patients with isolated systolic hypertension or albuminuria (all P<0.05). Compared to patients <65 years, older patients had higher pulse pressure, LV mass, and prevalence of concentric hypertrophy at baseline (78 vs 69 mmHg, 234 vs 224 g, and 28 vs 16%, respectively, all P<0.01), while the mean blood pressure did not differ. Over 4 years, reductions in LV mass and the mean blood pressure were similar in both groups, but older patients more often had residual hypertrophy (31 vs 15%, P<0.001) with a preponderance of eccentric geometry. In multivariate analysis of 4-year change in LV mass controlling for baseline mass, larger hypertrophy reduction was associated with losartan treatment, while age, gender, body mass index, and 4-year change in pulse pressure and albuminuria did not enter (Multiple R (2)=0.40, P<0.001). Thus, in up-to-80-year-old hypertensive patients with left ventricular hypertrophy, age did not significantly attenuate hypertrophy reduction during antihypertensive treatment, although residual hypertrophy was more prevalent in older patients as a consequence of higher initial LV mass.     

Night time blood pressure and cardiovascular structure in a middle-aged general population in northern Italy: the Vobarno Study.

The aim was to determine, in a cross-sectional study, the relation between structural alterations in the heart and carotid arteries, and blood pressure (BP) changes from day to night time, measured by ambulatory BP (ABP). In 225 untreated subjects (107 F, 118 M, age range 48-64 years) and 59 treated subjects (24 M, 35 F, age range 50-64), living in a small town of northern Italy (Vobarno, Brescia) carotid intima media thickness as well as the occurrence of plaque, were evaluated by ultrasound. Echocardiographic left ventricular (LV) mass was measured according to the Penn Convention. BP was determined by clinic measurement and by 24-h non-invasive ABP monitoring. Subjects were divided in two groups, according to the decrease of night time systolic BP (SBP) "dippers" (SBP decreased by at least 10% during night time) and "non-dippers" (decrease of night time SBP <10%). The intima-media thickness in the common carotid, in the carotid bifurcation, in the internal carotid artery and average intima-media thickness were significantly greater in untreated non-dippers as compared with dipper subjects (ANOVA P < 0.05). A significantly higher prevalence of plaque was observed in untreated non-dippers as compared with dippers (P = 0.002). After adjusting for age, sex, 24-h SBP, and smoking, IMT in the carotid bifurcation and average intima-media thickness remained significantly greater in non-dipper subjects (P < 0.05 for all comparisons). No significant differences in LV mass were observed between dippers and non-dipper subjects. In conclusion, in a general population of unselected middle-aged subjects, night time BP values, among other risk factors, seem to represent an important determinant of carotid wall structure.     

Quality control of B-mode ultrasonic measurement of carotid artery intima-media thickness: the European Lacidipine Study on Atherosclerosis

BACKGROUND: The European Lacidipine Study of Atherosclerosis (ELSA) was a prospective, randomized, double-blind, multinational interventional trial using B-mode ultrasound measurement of carotid intima-media thickness (IMT) in 2259 hypertensive individuals. ELSA showed that 4-year treatment with the calcium antagonist, lacidipine, significantly slowed down progression of carotid atherosclerosis as compared with treatment with the beta-blocker, atenolol. OBJECTIVE: To report data on cross-sectional and longitudinal quality control of the ultrasound measurements implemented throughout ELSA. METHODS: Patients underwent scans at baseline and at each annual visit. All endpoints were measured while the study was in progress (initial measurements). In addition to the cross-sectional quality control procedures, a longitudinal quality control procedure of re-reading 250 baseline scans at yearly intervals was implemented, to control possible reader drift. After the study had been completed, the primary endpoint was measured again under the same condition of cross-sectional quality control. RESULTS: Cross-sectional quality control data showed high reliability for all endpoints at all time points except for single maximum IMT (Tmax) and internal carotid IMT. Within-reader reliability was constantly better than between-reader reliability but, for the primary endpoint, between-reader reliability remained excellent. Initial and longitudinal quality control measurements showed a time trend toward lower IMT values. After application of a correction factor calculated from longitudinal quality control, all initial measurements no longer decreased with time, and the corrected IMT measurements were reasonably similar to those made after completion of the study. CONCLUSION: For long-term epidemiological studies and clinical trials, both cross-sectional and longitudinal quality control are critical to the reliability of measurements. In order to evaluate the absolute change in IMT and interpret study results without bias, both must be implemented.     

Comparison of actions of irbesartan versus atenolol on cardiac repolarization in hypertensive left ventricular hypertrophy: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation Versus Atenolol (SILVHIA)

Left ventricular (LV) hypertrophy is associated with a substantial risk for malignant arrhythmias and sudden death. The effects of antihypertensive therapy on QT dispersion, which reflects cardiac repolarization heterogeneity, in relation to changes in LV mass has not been well studied. Repeat echocardiography and QT measurements (standard 12-lead electrocardiograms) were performed in hypertensive patients with LV hypertrophy, who were randomized double-blind to receive the angiotensin II type 1-receptor blocker irbesartan (n = 44) or the beta(1)-receptor blocker atenolol (n = 48) for 48 weeks, and in 37 matched hypertensive control subjects without LV hypertrophy. LV mass index was related to QT dispersion (r = 0.34, p <0.001). The reduction in LV mass was greater using irbesartan than using atenolol (-27 +/- 28 vs -15 +/- 21 g/m(2) at 48 weeks, p = 0.021), with similar reductions in blood pressure. Irbesartan decreased QT dispersion (from 56 +/- 24 ms to 45 +/- 20 ms at 48 weeks; p <0.001) and QTc dispersion (from 57 +/- 24 to 44 +/- 19 ms at 48 weeks; p <0.001). In contrast, atenolol had minor effects. The decreases in QT and QTc dispersions were greater using irbesartan than using atenolol (p = 0.001 and p = 0.011, respectively); the same results were found when changes in LV mass, blood pressure, and heart rate were also included in multivariate analyses. Thus, heterogeneity of ventricular repolarization is related to the degree of LV hypertrophy. Irbesartan, but not atenolol, reduces QT and QTc dispersions independent of changes in LV mass, blood pressure, or heart rate, and thus seems to induce structural and electrical remodeling in a direction that could decrease the risk of fatal events in hypertensive patients.     

Maximum value of home blood pressure: a novel indicator of target organ damage in hypertension

The maximum office systolic blood pressure (SBP) has been shown to be a strong predictor of cardiovascular events, independently of the mean SBP level. However, the clinical implications of maximum home SBP have never been reported. We investigated the association between the maximum home SBP and target organ damage (TOD). We assessed the left ventricular mass index (LVMI) and carotid intima-media thickness (IMT) using ultrasonography and the urinary albumin/creatinine ratio (UACR) as measures of TOD in 356 never-treated hypertensive subjects. Home BP was taken in triplicate in the morning and evening, respectively, for 14 consecutive days with a memory-equipped device. The maximum home SBP was defined as the maximum mean triplicate BP reading in the 14-day period for each individual and was significantly correlated with LVMI (r=0.51, P<0.001), carotid IMT (r=0.40, P<0.001), and UACR (r=0.29, P<0.001). The correlation coefficients with LVMI and carotid IMT were significantly larger for the maximum home SBP than the mean home SBP. In multivariate regression analyses, the maximum home SBP was independently associated with LVMI and carotid IMT, regardless of the mean home BP level. In the prediction of left ventricular hypertrophy and carotid atherosclerosis, the goodness-of-fit of the model was significantly improved when the maximum home SBP was added to the sum of the mean office and home BPs (P=0.002 and P<0.001, respectively). These findings indicate that assessment of the maximum home SBP, in addition to the mean home SBP, might increase the predictive value of hypertensive TOD in the heart and artery.     

Sex-related difference in regression of left ventricular hypertrophy with antihypertensive treatment: the LIFE study

While left ventricular (LV) structure and function differ between hypertensive women and men, it remains unclear whether sex affects regression of LV hypertrophy with antihypertensive treatment. We analysed paired echocardiograms in 500 men and 347 women enrolled in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study at baseline and after 12 months of antihypertensive treatment with either losartan or atenolol. At enrollment, 177 women and 242 men were randomized to losartan-based treatment and 161 women and 247 men were randomized to atenolol-based treatment (sex difference=NS). After 12 months of antihypertensive treatment, blood pressure was lowered similarly in women (152/83 from 174/97 mmHg) and men (149/85 from 173/99 mmHg; both P<0.001, sex difference=NS), without significant change in body weight in either sex. Cardiac output and pulse pressure/stroke volume were equivalently reduced in both sexes (-0.2 vs -0.1 l/min and both -0.20 mmHg/ml/m(2), respectively; both P=NS). Absolute LV mass change after 12 months of antihypertensive treatment was greater in men than in women (-30 vs -24 g, P=0.01). However, after adjusting for baseline LV mass and randomized study treatment, LV mass reduction was greater in women than in men (-33 vs -23 g, P=0.001). LV mass regression was greater in women, by 8.0+/-2.8 g, after adjusting for baseline LV mass and randomized study treatment. After consideration of baseline LV mass and randomized study treatment, antihypertensive treatment regressed LV hypertrophy more in women. Further studies are needed to identify the mechanisms and prognostic implications of this sex-related difference.