José A.A. Cipolli

Sex-specific hemodynamic and non-hemodynamic determinants of aortic root size in hypertensive subjects with left ventricular hypertrophy

Aortic root (AoR) dilatation is more frequently observed in hypertensive individuals and is independently associated with left ventricular (LV) hypertrophy. Although the LV structure has sex-specific predictors, it remains unknown whether there are gender-related differences in the determinants of AoR size. We carried out a cross-sectional analysis of clinical, laboratory, anthropometric, funduscopic and echocardiographic features of 438 hypertensive patients with LV hypertrophy (266 women and 172 men). Women with enlarged AoR had higher cardiac output (P=0.0004), decreased peripheral vascular resistance (P=0.009), higher prevalence of mild aortic regurgitation (P=0.02) and increased waist circumference (P=0.04), whereas AoR-dilated men presented with a higher prevalence of concentric LV hypertrophy (P=0.0008) and mild aortic regurgitation (P=0.005) and increased log C-reactive protein levels (P=0.02), compared with sex-matched normal AoR subjects. In women, AoR dilatation associated with cardiac output, mild aortic regurgitation and waist circumference in a multivariate model including age, body surface area, height, homeostasis model assessment index, LV mass index, diastolic blood pressure, menopause status and use of antihypertensive medications as independent variables. Conversely, AoR dilatation associated with LV relative wall thickness, log C-reactive protein and mild aortic regurgitation without contributions from diastolic blood pressure, height, body surface area, LV mass index, peripheral vascular resistance and antihypertensive medications in men. Taken together, these results suggest that both volume overload and abdominal obesity are related to AoR dilatation in hypertensive women, whereas AoR enlargement is associated more with inflammatory and myocardial growth-related parameters in hypertensive men with LV hypertrophy.

Relationship between serum uric acid and internal carotid resistive index in hypertensive women: a cross-sectional study

BackgroundThe impact of serum uric acid (SUA) on arteries of hypertensive subjects remains to be fully established. This study investigated the relationship between SUA and carotid structural and hemodynamic parameters in hypertensive men and women.MethodsThree hundred and thirty eight patients (207 women and 131 men) were cross-sectionally evaluated by clinical, laboratory, hemodynamic and carotid ultrasound analysis. Common carotid diameters, circumferential wall tensions, Young’s Elastic Modulus, Stiffness Index, Arterial Compliance and intima-media thickness (IMT) were determined. Internal carotid artery resistive index (ICRI), a hemodynamic measure that reflects local vascular impedance and microangiopathy, was also assessed.ResultsUnivariate analysis showed no significant correlation of SUA with carotid diameters, elasticity/stiffness indexes, IMT and circumferential wall tensions in both genders. Conversely, SUA correlated with ICRI (r = 0.34; p < 0.001) in women, but not in men, and hyperuricemic women presented higher ICRI than normouricemic ones (0.684 ± 0.007 vs. 0.649 ± 0.004; p < 0.001). Stepwise and logistic regression analyses adjusted for potential confounding factors showed that ICRI was independently associated with SUA and hyperuricemia in women.ConclusionsThis study demonstrated that SUA was associated with ICRI in hypertensive women, suggesting that there might gender-related differences in the relationship between SUA and vascular damage in subjects with systemic hypertension.

Sodium Intake Is Associated with Carotid Artery Structure Alterations and Plasma Matrix Metalloproteinase-9 Upregulation in Hypertensive Adults

The mechanisms by which dietary sodium modulates cardiovascular risk are not fully understood. This study investigated whether sodium intake is related to carotid structure and hemodynamics and to plasma matrix metalloproteinase (MMP) activity in hypertensive adults. One hundred thirty-four participants were cross-sectionally evaluated by clinical history, anthropometry, carotid ultrasound, and analysis of hemodynamic, inflammatory, and metabolic variables. Daily sodium intake (DSI) was estimated by 24-h recall, discretionary sodium, and a FFQ. In 42 patients, plasma MMP-2 and MMP-9 activities were also analyzed. The mean DSI was 5.52 ± 0.29 g/d. Univariate analysis showed that DSI correlated with common carotid artery systolic and diastolic diameter (r = 0.36 and 0.34; both P < 0.001), peak and mean circumferential tension (r = 0.44 and 0.39; both P < 0.001), Youngs Elastic Modulus (r = 0.40; P < 0.001), intima-media thickness (r = 0.19; P < 0.05), and internal carotid artery resistive index (r = 0.20; P < 0.05). Multivariate analyses revealed that only artery diameter, circumferential wall tension, and Youngs Elastic Modulus were independently associated with DSI. Conversely, plasma MMP-9 activity was associated with DSI (r = 0.53; P < 0.001) as well as with common carotid systolic diameter (r = 0.33; P < 0.05) and Youngs Elastic Modulus (r = 0.38; P < 0.01). In conclusion, sodium intake is associated with carotid alterations in hypertensive adults independently of systemic hemodynamic variables. The present findings also suggest that increased MMP-9 activity might play a role in sodium-induced vascular remodeling.

Toll-like receptor 6 Ser249Pro polymorphism is associated with lower left ventricular wall thickness and inflammatory response in hypertensive women.

BACKGROUND Experimental data demonstrated that inactivation of toll-like receptor (TLR) pathway components attenuated left ventricular (LV) remodeling induced by pressure overload. This study investigated the impact of TLR6 Ser249Pro polymorphism on LV structure in hypertensive subjects. METHODS A sample of 443 patients (266 women and 177 men) was evaluated by clinical history, physical examination, analysis of inflammatory and metabolic parameters, echocardiography, and genotyping of the TLR6 variant. Moreover, the relationship between genotypes and in vitro responsiveness of peripheral blood monocytic cells to TLR agonists was also assessed. RESULTS Homozygous women for the TLR6 249Ser allele had lower LV posterior wall thickness (9.4 + or - 0.4 vs. 10.5 + or - 0.1 mm; P = 0.02), interventricular septum thickness (9.7 + or - 0.3 vs. 10.7 + or - 0.1 mm; P = 0.03), and LV relative wall thickness (0.39 + or - 0.02 vs. 0.44 + or - 0.01; P = 0.02) than women with other genotypes. These results were confirmed by stepwise regression analyses adjusted by potential confounders. Conversely, homozygous men for the 249Ser variant showed no differences in LV structure in comparison to males carrying the 249Pro allele. In addition, monocytes from hypertensive women homozygous for the 249Ser allele showed a lower release of tumor necrosis factor-alpha and interleukin-6 in response to zymosan (TLR6 agonist), but not to lipopolysaccharide (TLR4 agonist). CONCLUSION These data suggest that hypertensive women homozygous for the TLR6 249Ser polymorphism might exhibit lower LV wall thickness and reduced TLR6-mediated inflammatory response than females carrying the major allele.

The C242T polymorphism of the p22-phox gene (CYBA) is associated with higher left ventricular mass in Brazilian hypertensive patients.

BackgroundReactive oxygen species have been implicated in the physiopathogenesis of hypertensive end-organ damage. This study investigated the impact of the C242T polymorphism of the p22-phox gene (CYBA) on left ventricular structure in Brazilian hypertensive subjects.MethodsWe cross-sectionally evaluated 561 patients from 2 independent centers [Campinas (n = 441) and Vitória (n = 120)] by clinical history, physical examination, anthropometry, analysis of metabolic and echocardiography parameters as well as p22-phox C242T polymorphism genotyping. In addition, NADPH-oxidase activity was quantified in peripheral mononuclear cells from a subgroup of Campinas sample.ResultsGenotype frequencies in both samples were consistent with the Hardy- Weinberg equilibrium. Subjects with the T allele presented higher left ventricular mass/height2.7 than those carrying the CC genotype in Campinas (76.8 ± 1.6 vs 70.9 ± 1.4 g/m2.7; p = 0.009), and in Vitória (45.6 ± 1.9 vs 39.9 ± 1.4 g/m2.7; p = 0.023) samples. These results were confirmed by stepwise regression analyses adjusted for age, gender, blood pressure, metabolic variables and use of anti-hypertensive medications. In addition, increased NADPH-oxidase activity was detected in peripheral mononuclear cells from T allele carriers compared with CC genotype carriers (p = 0.03).ConclusionsThe T allele of the p22-phox C242T polymorphism is associated with higher left ventricular mass/height2.7 and increased NADPH-oxidase activity in Brazilian hypertensive patients. These data suggest that genetic variation within NADPH-oxidase components may modulate left ventricular remodeling in subjects with systemic hypertension.

The functional Toll-like receptor 4 Asp299Gly polymorphism is associated with lower left ventricular mass in hypertensive women

BACKGROUND This study investigated the impact of a putative functional TLR4 polymorphism (Asp299Gly) on left ventricular (LV) structure in hypertensive subjects. METHODS A sample of 443 patients (266 women and 177 men) was evaluated by clinical history, physical examination, anthropometry, analysis of inflammatory and metabolic parameters, echocardiography and TLR4 Asp299Gly genotyping. In addition, the relationship between the polymorphism and in vitro lipopolysaccharide responsiveness of peripheral blood monocytic cells was also assessed. RESULTS Women carrying the 299Gly allele presented lower posterior wall thickness (p=0.01), interventricular septum thickness (p=0.04), LV mass (p=0.01) and LV mass index (p=0.03), as well as a reduced prevalence of LV hypertrophy (p=0.002), in comparison to women with the wild-type genotype. These results were confirmed by stepwise and logistic regression analyses adjusted for potential confounders. Conversely, the 299Gly allele did not influence LV structure in men. Furthermore, in vitro assays revealed that monocytes of either men or women heterozygous for the 299Gly allele presented a lower lipopolysaccharide-induced production of interleukin-6, compared to non-carriers. CONCLUSIONS The functional TLR4 Asp299Gly polymorphism is associated with lower LV mass in hypertensive women. These findings suggest that interactions among gender, LV remodeling and TLR4 gene variants may occur in hypertensive subjects.

Gender influences the relationship between lung function and cardiac remodeling in hypertensive subjects

Hypertensive patients are predisposed to left ventricular (LV) remodeling and frequently exhibit decline in lung function as compared with the general population. Here, we investigated the association between spirometric and echocardiographic data in non-smoking hypertensive subjects and the role of gender in this regard. In a cross-sectional study, 107 hypertensive patients (60 women) enrolled from a university outpatient clinic were evaluated by clinical, hemodynamic, laboratory and echocardiographic analysis. Vital capacity, forced vital capacity (FVC), forced expired volume in 1 s (FEV1) and in 6 s (FEV6), FEV1/FVC ratio and FEV1/FEV6 ratio were estimated by spirometry. In women, higher LV mass index and E/Em ratio correlated with markers of restrictive lung alterations, such as reduced FVC (r=−044; P<0.001; r=−0.42; P<0.001, respectively) and FEV6 (r=−0.43; P<0.001; r=−0.39; P<0.01, respectively), while higher left atrial volume index correlated with markers of obstructive lung alterations, such as reduced FEV1/FVC (r=−055; P<0.001) and FEV1/FEV6 (r=−0.45; P<0.001) ratios. These relationships were further confirmed by stepwise regression analysis adjusted for potential confounders. In men, LV mass index correlated with FVC and FEV6, but these associations did not remain statistically significant after adjustment for confounding variables. Furthermore, inflammatory markers such as plasma C-reactive protein and matrix-metalloproteinases-2 and -9 levels did not influence the association between spirometric and cardiac parameters. In conclusion, these results indicate that LV remodeling is related to restrictive lung alterations while left atrial remodeling is associated with obstructive lung alterations in hypertensive women.

Mannose-binding lectin (MBL2) polymorphisms and inflammation in hypertensive patients.

We investigated the possible role of Mannose binding lectin 2 (MBL2) functional polymorphisms in the prevalence of hypertension and hypertensive end‐organ damage in 300 hypertensive patients and 313 normotensive individuals from Southern Brazil. Hypertensive subjects with MBL2 AO/OO genotypes presented lower C‐reactive protein levels than AA individuals and consequently lower inflammatory status.

Onset of hypertension during pregnancy is associated with long-term worse blood pressure control and adverse cardiac remodeling

Up to 20% of women with hypertensive pregnancy disorders might persist with chronic hypertension. This study compared clinical and echocardiographic features between women whose hypertension began as hypertensive pregnancy disorders (PH group) and women whose diagnosis of hypertension did not occur during pregnancy (NPH group). Fifty PH and 100 NPH women were cross-sectionally evaluated by clinical, laboratory, and echocardiography analysis, and the groups were matched by duration of hypertension. PH exhibited lower age (46.6 ± 1.4 vs. 65.3 ± 1.1 years; P < .001), but higher systolic (159.8 ± 3.9 vs. 148.0 ± 2.5 mm Hg; P = .009) and diastolic (97.1 ± 2.4 vs. 80.9 ± 1.3 mm Hg; P < .001) blood pressure than NPH, although used more antihypertensive classes (3.4 ± 0.2 vs. 2.6 ± 0.1; P < .001). Furthermore, PH showed higher left ventricular wall thickness and increased prevalence of concentric hypertrophy than NPH after adjusting for age and blood pressure. In conclusion, this study showed that PH may exhibit worse blood pressure control and adverse left ventricular remodeling compared with NPH.

Lung age is related to carotid structural alterations in hypertensive subjects

Hypertensive patients exhibit higher cardiovascular risk and reduced lung function compared with the general population. Whether this association stems from the coexistence of two highly prevalent diseases or from direct or indirect links of pathophysiological mechanisms is presently unclear. This study investigated the association between lung function and carotid features in non-smoking hypertensive subjects with supposed normal lung function. Hypertensive patients (n = 67) were cross-sectionally evaluated by clinical, hemodynamic, laboratory, and carotid ultrasound analysis. Forced vital capacity, forced expired volume in 1 second and in 6 seconds, and lung age were estimated by spirometry. Subjects with ventilatory abnormalities according to current guidelines were excluded. Regression analysis adjusted for age and prior smoking history showed that lung age and the percentage of predicted spirometric parameters associated with common carotid intima-media thickness, diameter, and stiffness. Further analyses, adjusted for additional potential confounders, revealed that lung age was the spirometric parameter exhibiting the most significant regression coefficients with carotid features. Conversely, plasma C-reactive protein and matrix-metalloproteinases-2/9 levels did not influence this relationship. The present findings point toward lung age as a potential marker of vascular remodeling and indicate that lung and vascular remodeling might share common pathophysiological mechanisms in hypertensive subjects.