Marina Crivaro

Cardiovascular risk factors, angiotensin-converting enzyme gene I/D polymorphism, and left ventricular mass in systemic hypertension

We investigated the influence of major cardiovascular risk factors (smoking, hypercholesterolemia, diabetes mellitus) on the association between angiotensin-converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphism and echocardiographic left ventricular mass in 225 patients with sustained hypertension, assessed by ambulatory blood pressure monitoring. When the study population was analyzed as a whole, the 3 ACE genotypes did not differ in left ventricular mass (II, 47 g/m2.7; ID, 49 g/m2.7; DD, 51 g/m2.7; p = NS). No difference was found in subjects (n = 135) in whom at least 1 major cardiovascular risk factor was present (II, 51 g/m2.7; ID, 51 g/m2.7; DD: 52 g/m2.7; p = NS). In contrast, in the absence of cardiovascular risk factors, DD subjects (n = 32) exhibited left ventricular mass index higher than non-DD (ID/II) subjects (n = 75; p <0.05). After controlling for age and sex, in the absence of cardiovascular risk factors, the risk of left ventricular hypertrophy was 3.8-fold higher in DD than in non-DD patients (odds ratio 3.8; 95% confidence interval 1.2 to 12.1, p <0.02). We conclude that in the present setting of patients with established sustained systemic hypertension, the absence of risk factors potentially affecting cardiovascular adaptation allows for the detection of a positive association between homozygosity for the D allele of the ACE gene and left ventricular hypertrophy.

Isolated office hypertension and end-organ damage

Background Patients with elevated blood pressure levels in the doctors office but normal blood pressures at other times have recently been described as having ‘isolated office hypertension’ (IOH). There is debate concerning whether this condition is really benign and thus not in need of treatment. Most of the previous studies on this topic included patients who had already been administered antihypertensive treatment, which unavoidably alters their cardiovascular profile. Objective To evaluate whether recently discovered and never-treated patients with isolated office hypertension have structural or functional abnormalities in comparison with normotensive controls. Methods Patients included in the study underwent 24 h ambulatory blood pressure monitoring, M-mode echocardiography and high-resolution echography of carotid arteries. Parameters of lipid and carbohydrate metabolism were also determined. Results We investigated 76 patients (20 with IOH and 56 with sustained hypertension) who had recently been diagnosed hypertensive but never been administered antihypertensive treatment and 32 matched controls. No changes were detected in left ventricular mass (LVM h2.7, 41.5 ± 11, 44.5 ± 10 and 41.5 ± 10 g/cm2.7 in IOH, sustained hypertension and controls, respectively) and in intimal–medial thickness (IMT, 0.54 ± 0.13, 0.59 ± 0.14 and 0.55 ± 0.16 mm, respectively). However, the left ventricular diastolic function was significantly different (E/A = 1.08 ± 0.3, 1.04 ± 0.3 and 1.43 ± 0.3, respectively, P = 0.02) and the carotid diameter significantly lower than that expected from the pressure–diameter relationship for normotensives. Conclusions These results, at variance with those of others, suggest that IOH affects the cardiovascular system even during the early phases of the disease and indicate the need for prospective clinical trials to evaluate the benefit from early treatment of IOH patients.

Clinic-daytime blood pressure difference and cardiovascular damage.

OBJECTIVE To investigate whether the clinic-daytime blood pressure difference can provide information on vascular reactivity to stress comparable to that of simple noninvasive stimuli such as a cold pressor test and isometric exercise, and whether there is any relationship between this blood pressure difference and noninvasive measurements of the left ventricular mass and carotid arterial wall. DESIGN Patients with newly discovered, never-treated, sustained hypertension were included in the study after a 1 month run-in, during which time their blood pressure was measured three times at 2 week intervals. METHODS Blood pressure was measured by a noninvasive procedure at rest and during a cold pressor test and an isometric exercise. The difference was calculated for systolic, diastolic and mean blood pressure as resting minus daytime ambulatory blood pressure. Parameters of the posterior wall and septal thickness of the left ventricle, aortic root and left atrium were studied by M-mode echocardiography. Carotid wall thickness and diameter were measured using ultrasound. RESULTS The 90 patients enrolled in the study were divided into tertiles of clinic-daytime blood pressure difference. The composition of the groups differed in sex, since the majority of women were in the highest tertile, but was comparable for age, body mass index, renin-aldosterone axis and lipid and carbohydrate metabolism. Blood pressure responses to cold and isometric exercise were more pronounced in patients in the lowest tertile of blood pressure difference. No intergroup differences were detected in echocardiographic parameters of ventricular (left ventricular mass, tertiles I-III: 46.5 +/- 10, 42.3 +/- 8, 44.8 +/- 13 g/m2.7, respectively) and carotid (intima-media thickness, tertiles I-III 0.58 +/- 0.1, 0.54 +/- 0.1, 0.62 +/- 0.1 mm, respectively) structure. CONCLUSIONS The present study indicates that the clinic-daytime blood pressure difference provides different information on cardiovascular reactivity compared with that obtained from the cold pressor test and isometric exercise. Moreover, it does not seem to have any relationship with ventricular hypertrophy and/or carotid wall thickening.

Influence of cardiovascular risk factors on relation between angiotensin converting enzyme-gene polymorphism and blood pressure in arterial hypertension.

Background The angiotensin-converting enzyme gene insertion (I)/deletion (D) polymorphism might be involved in the development of several cardiovascular diseases, but its role in humans remains controversial. Objective To investigate the relation between the angiotensin converting enzyme gene polymorphism and extent of blood pressure elevation in arterial hypertension, taking into account the influence of cardiovascular risk factors. Methods We studied 171 patients (aged 49 ± 9 years, 61 women) with abnormal clinic and 24 h ambulatory blood pressures, after a 3-week wash-out. Results We found no significant difference in clinic and ambulatory blood pressures among homozygotic D (DD), heterozygotic D (ID) and homozygotic I (II) angiotensin converting enzyme genotypes and between homozygotic D (DD) and pooled heterozygotic D (ID) plus homozygotic I (II) (non-DD) angiotensin converting enzyme genotypes. At least one additional cardiovascular risk factor (smoking, hypercholesterolaemia or diabetes) was present for 103 patients (33 DD and 70 non-DD). Non-DD subjects (n = 43) without additional cardiovascular risk factors exhibited lower values of 24 h, daytime systolic and pulse blood pressures than did members of all other groups (all P < 0.04). In the presence of risk factors, DD and non-DD subjects exhibited similar systolic and pulse ambulatory blood pressures, in that we found higher values in non-DD genotype subjects with risk factors than we did for non-DD subjects without additional risk factors. In multivariate analysis, the combination of non-DD genotype and absence of cardiovascular risk factors was associated with the lowest values of systolic and pulse blood pressures. Conclusions Angiotensin converting enzyme insertion allele appears clustered with lower ambulatory systolic and pulse blood pressures in hypertensive patients when the potential interference of additional cardiovascular risk factors is eliminated. A high prevalence of cardiovascular risk factors in population studies might blunt a possible biological association of blood pressure with DD genotype by contributing to raising of blood pressures also in subjects with non-DD genotypes.

Inappropriate left ventricular mass and angiotensin converting enzyme gene polymorphism

Under this scenario, it is poss-ible to discriminate between subjects with LVMappropriate to compensate an abnormal cardiacworkload at a given individual body size and gen-der, and those with LVM exceeding the value thatwould be normal for their loading conditions. Wetermed the latter condition ‘inappropriate LVM’. Inprevious reports we found that inappropriate LVMwas associated with relevant cardiovascular abnor-malities, suggesting that inappropriate LVM is ahigh-risk cardiac phenotype.