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ABSTRACT: Currently there is no consensus regarding which add-on therapy to use in resistant hypertension. This study was designed to compare two treatment options, spironolactone (SPR) versus dual blockade of the renin-angiotensin-aldosterone system (RAAS).
Forty-two patients with true resistant hypertension were included in the study. An open-label prospective crossover design was used to add a second RAAS blocker to previous treatment and then SPR following 1 month of wash-out. BP was measured in the office and by ambulatory blood pressure monitoring (ABPM). Changes in laboratory tests were also studied for both treatments. The predictive values of aldosterone-renin ratio (ARR) and serum potassium of determining the antihypertensive response were analyzed for both arms.
Following the first stage of dual blockade, SBP dropped significantly both in office (reduction of 12.9 ± 19.2 mmHg)) and by ABPM (reduction of 7.1 ± 13.4 mmHg). Office DBP was unchanged but was significantly reduced as measured by ABPM (3.4 ± 6.2 mmHg). On SPR treatment, office BP was reduced 32.2 ± 20.6/10.9 ± 11.6 mmHg. By ABPM the reduction was 20.8 ± 14.6/8.8 ± 7.3 mmHg (P < 0.001). The BP control was achieved by 25.6% of patients in dual blockade and 53.8% in SPR with office blood pressure. By ABPM, 20.5% were controlled on dual blockade and up to 56.4% with SPR. Serum potassium was a weak inverse predictor of the blood pressure-lowering effect of SPR.
SPR has a greater antihypertensive effect than dual blockade of the RAAS in resistant hypertension. SPR at daily doses of 25-50 mg shows a potent antihypertensive effect when added to prior regimes of single RAAS axis blockade in patients with resistant arterial hypertension.
Journal of hypertension 11/2010; 28(11):2329-35. · 4.02 Impact Factor
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ABSTRACT: To investigate the influence of metabolic syndrome (MS) on risk stratification and ulterior classification in hypertensive patients at entry into a hypertension unit by comparing the criteria of ESH-ESC 2003 and 2007 guidelines.
720 consecutive patients attending a hospital-located hypertension unit were included in the study. They were classified with or without MS according to the ATP-III 2005 report. Patients underwent repeated office BP measurements and routine blood/urine examinations. In addition ultrasensitive CRP (uCRP), echocardiogram, fasting insulin, urinary albumin excretion were determined and HOMA index was calculated.
The prevalence of MS was 58.8 %. Abdominal obesity and fasting glucose were the most prevalent components of MS, and HDL-cholesterol the least prevalent. MS group had higher levels of LDL-cholesterol and higher prevalence of left ventricular hypertrophy and microalbuminuria. Patients with MS also presented a significant elevation in uCRP, fasting insulin and HOMA. BP was controlled in 55.6%. When we applied the 2003 guideline, 48.9% patients showed a high or very high added cardiovascular risk. With the applications of the 2007 guide the prevalence of this two categories reach 73.9%.
A significant difference in the risk pattern distribution is found when MS is considered in risk stratification in our hypertensive population. The accompanying increase in the levels of other cardiovascular risk factors and in the prevalence of target organ damage justifies the global intervention on cardiovascular risk recommended by 2007 ESH-ESC guidelines.
Therapeutic Advances in Cardiovascular Disease 03/2010; 4(2):97-103.
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ABSTRACT: To investigate the prevalence of anti-C-reactive protein (CRP) autoantibodies in patients with systemic lupus erythematosus (SLE) and non-SLE patients with persistent antiphospholipid antibodies (aPL) and their association with clinical manifestations.
Sera of 137 patients with SLE, 127 with persistent aPL and 30 with idiopathic venous thromboembolic disease, were assayed for the presence of anti-CRP reactivity by ELISA. Associations of anti-CRP reactivity with clinical features, with other autoantibodies, and with serum concentrations of C3 and CRP were assessed.
Antibodies against CRP were seen in 51% (n = 137) of patients with SLE and in 54% (n = 127) of patients with aPL. SLE patients with anti-CRP antibodies showed increased frequencies of anti-dsDNA and aPL antibodies compared to those without anti-CRP (52% vs 26% and 68% vs 31%, respectively). Mean serum C3 levels were lower in the subgroup of patients with SLE positive for anti-CRP antibodies (79 +/- 25 vs 92 +/- 25 mg/dl; p = 0.004 ) and mean serum CRP levels were significantly higher (13 +/- 17 vs 5 +/- 8 mg/l; p = 0.01 ). The frequency of nephritis was higher in SLE patients with anti-CRP antibodies, than in those without (27% vs 13%; p = 0.058). In patients with clinical and serological evidence of antiphospholipid syndrome (APS) the frequency of anti-CRP antibodies was significantly higher than in asymptomatic aPL carriers, in both SLE patients [85% (23 of 27) vs 59% (19 of 32); p = 0.021] and non-SLE patients [76% (38 of 50) vs 19% (9 of 47); p < 0.001]. Among patients with APS with or without SLE, 26 had arterial events, 31 had venous events, 6 had combined arterial and venous events, and 14 had fetal loss. Mean titers of IgG anti-CRP (29 +/- 21, 30 +/- 19, 60 +/- 37, and 26 +/- 12 AU/ml) and frequencies of anti-CRP antibodies (88%, 71%, 50%, and 71%) in these subgroups of patients were comparable.
We confirmed the high prevalence of anti-CRP autoantibodies both in patients with SLE and in non-SLE and aPL-positive patients. We observed that the presence of these antibodies was associated with lupus nephritis and with clinical features of the APS in patients with lupus and non-lupus patients.
The Journal of Rheumatology 10/2006; 33(10):1980-6. · 3.69 Impact Factor
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ABSTRACT: Left ventricular hypertrophy increases the risk for cardiovascular target organ damage, myocardial infarction, and stroke. The authors assessed the patterns of ventricular adaptation in 107 essential hypertensives whose treatment had been withdrawn and its modification after 1 year of hypertension treatment. Blood pressure decreased from 158+/-17/96+/-12 mm Hg to 137+/-15/83+/-10 mm Hg (mean +/- SD; p<0.001); 45% of the patients (49 of 107) had their blood pressure controlled below 140 mm Hg and 90 mm Hg. Although a significant decrease of left ventricular mass index was found in the study, the percentage of patients with normal left ventricular geometry at the completion of the study increased by only 9% (27% to 36%, p>0.05). Left ventricular mass geometry improved in 31% of the patients, remained unaffected in 51%, and worsened in 18%. The data suggest that even while suboptimal antihypertensive treatment reduces left ventricular mass index, either left ventricular hypertrophy or concentric remodeling remains present in a significant number of patients at the end of a 1-year treatment period. The authors conclude that these patients should be considered as a subgroup at high risk and should be treated more aggressively.
Journal of Clinical Hypertension 06/2005; 7(6):333-8. · 1.83 Impact Factor
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ABSTRACT: Recent findings have demonstrated that plasma C-reactive protein levels predict restenosis after coronary angioplasty. Furthermore, C-reactive protein levels have also been shown to be heritable. However, no genetic-epidemiological data are available on the relationship between genetic variants of C-reactive protein (CRP) gene and risk of restenosis after angioplasty. The present study was carried out to examine the possible association of a non-sense exonic 1059G > C and an intronic T > A C-reactive protein gene polymorphisms in a large, previously described, well-characterized cohort of 779 post-angioplasty patients of whom 342 subjects developed restenosis. Genotype distributions were in Hardy-Weinberg equilibrium. Genotype and allele distributions were similar between cases and controls. Haplotype frequency distributions were also similar between cases and controls. Further investigation using a haplotype-based logistic and linear regression analyses, adjusting for potential confounders, yielded similar null results. In conclusion, we found no evidence for an association between the polymorphisms/haplotypes thereof tested and restenosis after angioplasty.
Atherosclerosis 11/2004; 176(2):393-6. · 3.79 Impact Factor
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ABSTRACT: Single-nucleotide polymorphisms (SNPs) are commonly used to study genetics for common diseases and predict pharmacological response. The selection of likely informative SNPs in association studies depends on their allele frequencies and on the linkage disequilibrium (LD) between SNPs, both of which may show interethnic differences. Among three populations consisting of 207 Chinese, 858 French, and 395 Spanish, we compared the allele frequency distributions of 64 intragenic SNPs of 35 candidate genes for cardiovascular diseases. Twenty-eight of these SNPs from 12 genes were also examined for intragenic LD. About 20% of SNPs were restricted to Europeans, being monomorphic in Chinese, among them mostly nonsynonymous coding SNPs and noncoding SNPs. Only 1.6% of SNPs were specific in Chinese, commensurate with the detection of these SNPs almost exclusively in Caucasians. Similarly, these SNPs were more often rare (<0.1 minor allele frequency) in Chinese (44.3%) than in Europeans (31.1%). The variant allele frequencies and intermarker LDs in terms of D' and Delta(2) were highly correlated between French and Spanish populations (r = 0.98-0.99, p < 0.001). However, only moderate correlations of allele frequencies and D' were found between the Chinese and the European populations (r = 0.7 and 0.3, respectively) despite a high correlation of Delta(2) values (r = 0.8). These results suggest that ethnic considerations are important in the selection of SNPs for association studies of candidate genes, as this may affect the power of the study as well as the likelihood of asking relevant questions and getting medically meaningful answers.
Genomics 04/2004; 83(4):559-65. · 3.02 Impact Factor
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ABSTRACT: The tumor suppressor gene product, in particular tumor suppressor protein p53 (TP53), has been suggested to play a role in post-angioplasty restenosis. However, no genetic-epidemiological studies relating to TP53 gene polymorphism(s) and the incidence of post-angioplasty restenosis are available. TP53 11951_11966dup16bp, R72P, and 13494G>A polymorphisms were characterized in a cohort of 779 patients, of whom 342 cases had developed restenosis (as defined by >50% loss of lumen compared with immediate post-procedure results) at repeat quantitative coronary angiography at six months post angioplasty. The haplotype-frequency distribution was marginally different between cases and controls with restenosis risk (chi(2)(7df)=13.08, P=0.070). Multivariable haplotype-based logistic regression indicated that haplotypes 16bp(-) -P72-G13494 [corrected], and 16bp(+) -P72-A13494 [corrected] exhibit protective effects on restenosis risk (odds ratio=0.58, 95%CI=0.40-0.83, P=0.0033; odds ratio=0.69, 95%CI=0.48-0.99, P=0.049, respectively). Multivariable haplotype-based linear regression again showed similar, significant association with degree of lumen loss. The present findings indicate protective effects of TP53 16bp(-) -P72-G13494 [corrected], and 16bp(+) -P72-A13494 [corrected] haplotypes in the incidence of restenosis after angioplasty. Furthermore, our study demonstrates that a haplotype-based approach can be more informative than a single-marker or marker-by-marker analysis.
Human Genetics 03/2004; 114(4):386-90. · 5.07 Impact Factor
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ABSTRACT: A polymorphic marker of the gene encoding the interleukin-1 (IL-1) receptor antagonist has been recently reported to be associated with risk of coronary artery disease. However, no prospective studies of the IL-1 gene cluster in relation to the occurrence of restenosis, a major complication of percutaneous transluminal coronary angioplasty (PTCA), have so far been conducted. We had the opportunity to investigate this question in a large, prospective cohort characterized by quantitative coronary angiography in all subjects. The IL1A A114S, IL1B -511C>T, IL1B 3953T>C, IL1RI exon1B T>C, and IL1RN VNTR (intron 2) polymorphisms were characterized in a cohort of 779 patients of whom 342 ("cases") had developed restenosis (as defined by >50% loss of lumen compared to immediate post-procedure results) at repeat angiography at 6 months post-PTCA. All observed genotype frequencies were in Hardy-Weinberg equilibrium. Frequencies for the rare alleles were: IL1A S, 0.29 (cases), 0.28 (controls); IL1B T, 0.31 (cases), and 0.33 (controls); IL1B C, 0.23 (cases), 0.24 (controls); IL1RI C, 0.34 (cases), 0.35 (controls); and IL1RN 2, 0.29 (cases), 0.29 (controls), respectively. There was no evidence for an association between genotype and restenosis or degree of lumen loss (adjusted for covariables). Our data indicate that the common variants in the IL-1 cluster genes are not associated with incidence of restenosis after PTCA.
Atherosclerosis 12/2003; 171(2):259-64. · 3.79 Impact Factor
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ABSTRACT: Even with optimal blood pressure control, organ protection may also depend on the selected therapeutic regime. Angiotensin-converting enzyme inhibitors have been shown to provide excellent organ protection in hypertension, and may show dose-dependent protective effects. Adrenergic alpha blockers have been associated with an increased rate of heart failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and Vasodilator-Heart Failure Trial (V-HeFT). This has been related to a proapoptotic effect of this drug in cardiomyocytes. Our purpose is to compare the heart and renal protection of a high quinapril dose, with a combined low quinapril dose plus doxazosin, in an animal model of chronic hypertension.
Uninephrectomized spontaneously hypertensive 12-week-old rats were treated for 36 weeks with either quinapril or a combination of doxazosin plus a low quinapril dose. Tight blood pressure control was achieved with both treatments. Renal and cardiac protection was assessed by different parameters, and cardiac apoptosis was evaluated by active caspase-3, apoptotic protein and heat shock protein levels. Untreated hypertensive and normotensive rats were included as controls.
Both treatments showed significant heart and renal protection compared with untreated animals. Both therapeutic regimes showed similar protection in renal and cardiac pathology, coronary media fibrosis, myocardial apoptosis and cardiac index. Proteinuria and left ventricular hypertrophy regression were significantly lower in the quinapril group compared with the combined treatment group.
Blood pressure control with a high quinapril dose provided higher organ protection than a combined therapy with a lower quinapril dose. This effect was not due to a deleterious effect of doxazosin.
Journal of nephrology 19(5):588-98. · 1.65 Impact Factor
