J Gasowski

Antihypertensive treatment modulates the association between the D/I ACE gene polymorphism and left ventricular hypertrophy: a meta-analysis

This meta-analysis attempted to derive pooled estimates for the putative association between echocardiographic or electrocardiographic left ventricular hypertrophy and the deletion/insertion (D/I) polymorphism of the angiotensin-I converting enzyme. Case-control studies were combined, using the Mantel and Haenszel approach. Joint P-values for continuous variables were calculated by Stouffer’s method. Continuous measurements of left ventricular mass, which were reported in different units, were expressed on a percentage scale using the within-study mean of the II genotype as the denominator. The computerised database used for this analysis, included 28 reports with an overall sample size of 6638 subjects. The prevalence of the D allele was significantly lower in Japanese (37.2%) than in Caucasians (56.2%). A funnel plot including 12 case-control studies (4094 subjects) suggested that no publication bias was present. Overall, left ventricular hypertrophy was not associated with the D allele. Compared with the II genotype, the excess risks of left ventricular hypertrophy associated with DD and DI genotypes were only 14% (95% CI: 0.92–1.42; P = 0.23) and 5% (95% CI: 0.87–1.28; P = 0.61), respectively. However, the sensitivity analysis showed that in untreated hypertensive patients the DD genotype, compared with II homozygozity, was associated with a 192% (P = 0.002) higher risk of left ventricular hypertrophy. If left ventricular mass was analysed as a continuous trait across 23 studies (5438 subjects), overall no association with the D/I polymorphism was present. However, if untreated hypertensive patients were analysed separately, echocardiographic left ventricular mass was on average 10.1% (95% CI: 4.8–15.5%; P = 0.001) higher in DDhomozygotes than in the II reference group. Thus, in untreated hypertensive patients, in case-control studies as well as association studies, the D allele behaved as a marker for left ventricular hypertrophy. These findings support the hypothesis that the enhanced ACE activity associated with the D allele may promote left ventricular hypertrophy if a pathophysiologic process causing this disorder, remains unopposed by treatment.

Systolic Hypertension in Europe (Syst-Eur) Trial Phase 2: objectives, protocol, and initial progress

The Systolic Hypertension in Europe (Syst-Eur) trial proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in older (⩾60 years) patients with isolated systolic hypertension (systolic BP ⩾160 mm Hg and diastolic BP <95 mm hg). after the completion of the syst-eur trial on 14 february 1997, 3506 consenting patients (93.0% of those eligible) were enrolled in phase 2 of the syst-eur trial. this open follow-up study aims to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine. to lower the sitting systolic bp below 150 mm hg (target bp), the first-line agent nitrendipine (10–40 mg/day) may be associated with enalapril (5–20 mg/day), hydrochlorothiazide (12.5–25 mg/day), both add-on study drugs, or if required any other antihypertensive agent. on 1 november 1998, 3248 patients were still being followed, 86 patients had proceeded to non-supervised follow-up, and 43 had died. the median follow-up in syst-eur 2 was 14.3 months. at the last available visit, systolic/diastolic bp in the patients formerly randomised to placebo (n = 1682) or active treatment (n = 1824), had decreased by 13.2/5.2 mm Hg and by 4.6/1.6 mm Hg, respectively, so that the between-group BP difference was 1.7 mm Hg systolic (95% Cl: 0.8 to 2.6 mm Hg; P < 0.001) and 0.9 mm hg diastolic (95% cl: 0.4 to 1.5 mm mm hg; P < 0.001). at the beginning of syst-eur 2, the goal bp was reached by 25.4% and 50.6% of the former placebo and active-treatment groups; at the last visit these proportions were 55.9% and 63.1%, respectively. at that moment, 45.9% of the patients were on monotherapy with nitrendipine, 29.3% took nitrendipine in combination with other study drugs. until the end of 2001, bp control of the syst-eur 2 patients will be further improved. cardiovascular complications and adverse events, such as cancer or gastro-intestinal bleeding, will be monitored and validated by blinded experts.

The relationship between pulse wave velocity and indexes of collagen synthesis in hypertensive patients, according to the level of systolic blood pressure

Vascular stiffening, a process responsible for the development of isolated systolic hypertension, depends on dysregulation of collagen–elastine production and arrangement, yet it is not known whether the effect is uniform throughout wide blood pressure (BP) range. To check whether arterial stiffness is similarly related to increased fibrotic remodelling, in patients with systolic blood pressure (SBP) above and below 160 mmHg. Consecutive peri- and postmenopausal female outpatients treated for hypertension and free from other disorders interfering with fibrotic processes, had their BP, pulse wave velocity (PWV), and collagen (N-terminal procollagen type III propeptide (PIIINP); C-terminal procollagen type I propeptide—(PICP)) measured. The average age of 100 women was 71.8±10.5 years, BP was 145/83±25/15 mmHg, pulse pressure 63±17 mmHg, and mean blood pressure (MBP) 104±17 mmHg. PWV was 12.9±3.6 m/s and was significantly higher among 30 patients with SBP of ⩾160 mmHg. PIIINP averaged 4.6±1.6 ng/ml and PICP 142.2±47.0 ng/ml. In the low SBP (<160 mmHg) group there was no relationship between PWV and collagen concentrations. However, in the ⩾160 mmHg group there was significant correlation between PWV and PIIINP concentration. The relationship held significant after adjustment for age, and BP components. Our result can help explaining the results of recent intervention trials where older patients tended to benefit more from potentially antifibrotic drugs (ACE-I), whereas those with compliant arteries tend to benefit from diuretics.

P.078 REFERENCE VALUES IN WHITE EUROPEANS FOR THE ARTERIAL PULSE WAVE RECORDED BY MEANS OF THE SPHYGMOCOR DEVICE

Measurement of blood pressure together with applanation tonometry at the radial artery allows the reproducible assessment of various indexes of arterial stiffness, including the peripheral (PPp) and central pulse pressures (PPc) and the peripheral (AIp) and central augmentation indexes (AIc). We defined preliminary diagnostic thresholds, using the distributional characteristics of these hemodynamic measurements in a reference population. We randomly recruited 870 subjects from 3 European populations. PPp was the average difference between systolic and diastolic blood pressure measured five times at one home visit. For measurement of PPc, AIp and AIc, we used the SphygmoCor device. We selected subjects without hypertension, diabetes, dyslipidemia in need of medical treatment or previous or concomitant cardiovascular disease. The study population included 228 men and 306 women (mean age 34.9 years). All hemodynamic measurements were curvilinearly related to age, and AIp and AIc were lower in men than in women. In men at age 40, the upper 95% prediction bands of the relations of the hemodynamic measurements with age approximated 60 mmHg for PPp, 40 mmHg for PPc, 90% for AIp, and 30% for AIc. For PPc, AIp and AIc, these thresholds must be adjusted for age, leading to lower and higher thresholds at younger and older age, respectively. In addition, in women of any age, the AIp and AIc thresholds must be increased by 10% and 7%, respectively. Pending validation in prospective outcome studies, distributional characteristics of arterial stiffness indexes in a reference population can be used to generate operational thresholds for use in clinical practice. (Hypertens Res 2006; 29: 475‐483)

Potentially positive ageing-related variations of medial smooth muscle cells in the saphenous veins used as aortocoronary bypass grafts

INTRODUCTION Currently, elderly people constitute a large proportion of patients undergoing coronary artery bypass grafting (CABG). Activated smooth muscle cells in the tunica media of saphenous vein (SV) grafts are thought to play a key role in the formation of neointima and development of occluding atherosclerotic plaques. The aim of this study was to identify ageing-related variations in the expression of the smooth muscle cells pro-teins that may impact on patency rate of the grafts and the CABG outcomes. MATERIAL AND METHODS The study involved 216 consecutive patients with the mean of 62.7 ± 8.4 years who underwent isolated CABG with at least one SV aortocoronary bypass graft. Expression of a-smooth muscle actin (a-SM actin), smooth muscle-myosin heavy chain (SM-MHC), calponin (CALP), cytokeratin 8 (CK-8), metalloproteinase-2 (MMP-2) and tissue inhibitors of metalloproteinases-2 and -3 (TIMP-2, TIMP-3) in the SV wall was assessed by immunohistochemistry and correlated with the age of patients. RESULTS Calponin and a-SM actin were expressed in all studied SV transplants. SM-MHC immunoreactivity was observed in SV segments in 68.5% of patients, whereas MMP-2a and TIMPs expression was found in 75% of cases. In more than 50% of analyzed SV transplants, no expression of cytokeratin-8 was found. Moderate correlations between preexisting expressions of either cytoskeletal or hemostatic proteins in the tunica media of the SV grafts and the age of CABG patients were demonstrated. They were positive for SM-MHC (r = 0.494), CALP (r = 0.548), TIMP-2 (r = 0.413) and TIMP-3 (r = 0.406) whereas negative for CK-8 (r = -0.528) and MMP-2 (r = -0.417). CONCLUSIONS Age-dependent decreases in the expression of MMP-2 and CK-8 accompanied by increases in expression of SM-MHC, TIMP-2 and TIMP-3 may promote SV graft patency and, thus, suggest a rationale for common use of SV grafts in the elderly.