Blood pressure, risk of ischemic cerebrovascular and ischemic heart disease, and longevity in alpha(1)-antitrypsin deficiency: the Copenhagen City Heart Study (original) (raw)
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The prevalence of hypertension (HTN) associated with alpha-1 antitrypsin deficiency (AATD) has been studied with indeterminate results. The aim of the study was to prospectively compare the prevalence of HTN before testing in 3 groups of individuals with subsequently normal, moderately deficient, and severely deficient genotypes of AATD with adjustment for differences in demographics and clinical variables. Methods: We performed a cross sectional study using data from the Alpha-1 Coded Testing (ACT) study. The univariate demographic and clinical factors associated with HTN were further analyzed by logistic regression analysis. Results: The prevalence of HTN was 27.2%, 20.6%, and 27.9% for individuals with normal, moderate and severe AATD, respectively (p<0.02). The prevalence of HTN increased with age and Kumbhare et al.; BJMMR, 5(7): 880-888, 2015; Article no.BJMMR.2015.095 881 an interaction between age, alpha-1 antitrypsin deficiency genotype and HTN was identified. The relative risk of HTN among young moderately deficient individuals was 0.53 (95% CI 0.37-0.76) the risk of young PiMM and PiMS (normal genotype) individuals. There was no significant difference in the risk in older moderately deficient individuals 1.02 (95% CI 0.76-1.37) and individuals with severe AATD 1.10 (95% CI 0.71-1.68) when compared to normal genotypes. Conclusion: Moderate deficiency genotypes (PiMZ, PiSS, PiMNull) have less HTN than normal or severe deficiency genotypes, particularly in young individuals. We speculate that protease inhibitor deficiency over a lifetime allows unopposed proteolysis of vascular connective tissue.Measured comorbidities do not explain these findings. Validation of this data should occur in other AATD cohorts.
Progression of Atherosclerosis Is Associated With Variation in the alpha1-Antitrypsin Gene
Arteriosclerosis, Thrombosis, and Vascular Biology, 2003
Objective— α 1 -Antitrypsin (AAT) protects elastic tissue and may play a role in atherogenesis. The association of atherosclerosis progression with common AAT variants was considered in 2 clinical trials. Methods and Results— We examined the association of AAT V213A, S and Z deficiency alleles, and the functional 3′ UTR 11478G>A with change in minimal luminal diameter, a measure of focal disease, in the Lopid Coronary Angiography Trial gemfibrozil study of post-bypass men. S or Z carriers (n=14) showed strong progression of disease on placebo (11.5%) but responded well to treatment (3% regression). 11478A carriers treated with placebo or gemfibrozil showed significantly more disease progression (n=8, −14.5% and n=16, −4.0%, respectively) than 11478GG men (n=107, −7.0% and n=108, −1.4%, respectively; overall, P =0.003). VV213 men treated with gemfibrozil (n=68) showed −4.8% progression, whereas A213 carriers (n=55) showed +1.4% regression of disease ( P =0.001). No V213A effect wa...
Cardiovascular risk in patients with alpha-1-antitrypsin deficiency
Respiratory Research
Background: Alpha-1-antitrypsin deficiency (AATD) is a rare inherited condition caused by mutations of the SERPINA1 gene that is associated with the development of a COPD like lung disease. The comorbidities in patients with AATDrelated lung diseases are not well defined. The aim of this study was to analyze the clinical phenotype of AATD patients within the German COPD cohort study COSYCONET ("COPD and SYstemic consequences-COmorbidities NETwork") cohort focusing on the distribution of comorbidities. Method and results: The data from 2645 COSYCONET patients, including 139 AATD patients (110 with and 29 without augmentation therapy), were analyzed by descriptive statistics and regression analyses. We found significantly lower prevalence of cardiovascular comorbidities in AATD patients as compared to non-AATD COPD patients. After correction for age, pack years, body mass index, and sex, the differences were still significant for coronary artery disease (p = 0.002) and the prevalence of peripheral artery disease as determined by an ankle-brachial-index <= 0.9 (p = 0.035). Also the distribution of other comorbidities such as bronchiectasis differed between AATD and non-deficient COPD. Conclusion: AATD is associated with a lower prevalence of cardiovascular disease, the underlying mechanisms need further investigation.
International Journal of Chronic Obstructive Pulmonary Disease, 2020
Background: Severe alpha-1-antitrypsin deficiency (AATD) is an established risk factor for chronic obstructive pulmonary disease (COPD) and liver disease, but the effect on the incidence of ischemic heart disease (IHD) is not well known. The aim was to evaluate the risk of incident IHD in patients with severe AATD compared with a random sample of the general population, with known smoking habits. Methods: AAT-deficient individuals, phenotype PiZZ (n=1545), were included in the Swedish National AATD Register. Controls (n=5883) were selected from population-based cohorts in Northern Sweden. Data on IHD and comorbidities were obtained by nationwide cross-linkage with the Swedish National Patient Register. Risk factors for incident IHD were analyzed using Cox regression, adjusted for age, gender, smoking status and the presence of COPD, hypertension, hyperlipidemia and diabetes. Results: At inclusion, 46% of the PiZZ individuals and 53% of the controls were neversmokers. During follow-up (median 16 years; range 0.2-23), 8% (n=123) of PiZZ individuals and 12% (n=690) of controls developed IHD. The controls had a significantly higher risk for incident IHD than the PiZZ individuals, with adjusted hazard ratio (HR) of 1.8 (95% CI 1.4-2.3). The risk was higher for controls in both ever-smokers (HR 2.1; 95% CI 1.5-2.9) and never-smokers (HR 1.5; 95% CI 1.1-2.2). Conclusion: PiZZ individuals have a lower risk of developing incident ischemic heart disease than the control subjects with known smoking habits, who had been randomly selected from population-based cohorts.
Serum alpha-1-antitrypsin level in Iraqi patients with coronary heart disease
Journal of Biotechnology Research Center
This study was designed to estimate the level of serum alpha -1- antitrypsin in patients with coronary heart disease. Patients were clinically subdivided into stable angina 25 patients, unstable angina30 patients and myocardial infarction 50 patients. A control sample of 30 individuals was matched with patient for age and sex.Non-significant elevation of serum alpha one antitrypsin were noted in MI cases compared to healthy control individuals, even some MI patients showed decreasing level of alpha one antitrypsin, which may return to hereditary alpha one antitrypsin deficiency in Iraqi patients.The Stable angina patients group showed non-significant decrease in alpha one antitrypsin level compared to healthy control, while unstable angina patients group showed significant decrease in alpha one antitrypsin level that will may facilitate developing disease towards MI. All present results need additional studies to be carried out on larger samples of Iraqi individuals and alpha one an...
Aging, carotid artery distensibility, and the Ser422Gly elastin gene polymorphism in humans
2001
Elastin is a protein of the extracellular matrix that forms the major component of elastic fibers from the arterial wall thickness and plays an important role in elastic properties of large blood vessels. To study the relationships between the Ser422Gly polymorphism in exon 16 of the gene-encoding elastin and the distensibility of 2 different arteries, the radial artery (a muscular artery) and the common carotid artery (an elastic artery), we studied a cohort of 320 subjects (49Ϯ12 years of age) without evidence of cardiovascular disease and who had never been treated with cardiovascular drugs. Distensibility and elastic modulus were evaluated for the common carotid and the radial arteries with high-resolution echo-tracking devices (NIUS-02 and Wall Track System). The A-to-G nucleotide change corresponding to the Ser422Gly amino acid change was studied by digestion of polymerase chain reaction products with BstNI. Results indicate that genotype frequencies (AAϭ10%, AGϭ51%, GGϭ39%) were in agreement with the Hardy-Weinberg equilibrium. For the carotid artery, a significant decrease in distensibility was observed in subjects carrying the A allele (with AAϩAG genotypes) compared with subjects with the GG genotype (13.8Ϯ6.4 kPa Ϫ1 • 10 Ϫ3 versus 15.9Ϯ6.2 kPa Ϫ1 • 10 Ϫ3 , PϽ0.01), assuming a dominant effect of the A allele. Moreover, the presence of the A allele was associated with a significant increase in elastic modulus (0.98Ϯ0.40 kPa • 10 3 in subjects with AAϩAG genotypes versus 0.83Ϯ0.41 kPa • 10 3 in subjects with GG genotypes, PϽ0.01). Multivariate analysis indicated that these results were observed after adjustment for age, gender, and mean arterial blood pressure (PϽ0.01). In contrast, no association was found between arterial parameters and genotypes for the radial artery. The 2-way analysis of covariance adjusted for mean arterial blood pressure indicated that the association between the A allele and distensibility of the carotid artery was observed only in subjects Ͼ50 years of age, assuming for carotid distensibility a significant age effect (PϽ0.01), genotype effect (Pϭ0.01), and age-genotype interaction (Pϭ0.04). The present results indicate a relationship between the Ser422Gly polymorphism and the distensibility of elastic arteries but not of muscular arteries and suggest that there is an age-genotype interaction for carotid artery distensibility.
Angiotensin-converting enzyme deletion allele is beneficial for the longevity of Europeans
AGE, 2011
The human angiotensin converting enzyme (ACE) gene is one of the most investigated candidate genes for cardiovascular diseases (CVD), but the understanding of its role among the elderly is vague. Therefore, this study focuses at: (a) testing the association of ACE polymorphism with CVD risk factors among the elderly, and (b) detecting the possible unequal distribution of ACE genotypes between senescent and younger segments of the European populations. The association of ACE I/D polymorphism with CVD health status [hypertension (HT), obesity, dislypidemia] in 301 very old subjects (88.2±5 years; F/M=221/80) was tested by means of logistic regression analysis. The meta-analysis of D allele frequency in general vs. elderly (80+ years) groups was conducted using all publicly available data for European populations comprising both age cohorts. Multiple multinomial logistic regression revealed that within this elderly sample, age (younger olds, 80-90 years), female sex (OR=3.13, 95% CI= 1.59-6.19), and elevated triglycerides (OR=2.53, 95% CI=1.29-4.95) were positively associated with HT, while ACE polymorphism was not. It was also established that the DD genotype was twice as high in 80+ cohort compared to general population of Croatia (p<0.00001). This trend was confirmed by the metaanalysis that showed higher D allele frequencies in olds from nine of ten considered European populations (OR=1.19, 95% CI=1.08-1.31). The data in elderly cohort do not confirm previously reported role of ACE DD genotype to the development of HT. Moreover, meta-analysis indicated that ACE D allele has some selective advantage that contributes to longevity in majority of European populations.
Investigating the Link between Alpha-1 Antitrypsin Deficiency and Abdominal Aortic Aneurysms
Annals of Vascular Surgery, 2021
Background: Alpha-1-Antitrypsin (AAT) is one of the major plasmatic protease inhibitors. In the last decade, an association between Alpha-1-Antitrypsin Deficiency (AATD) and Abdominal Aortic Aneurysms (AAA) has been hypothesized. Multiple factors may be involved in AAA's etiopathogenesis, and an underlying structural defect of the extracellular matrix (ECM) is always present. AATD could be a reasonable risk factor for AAA because it is related to protease/antiprotease imbalance and enhanced ECM degradation of the vessel wall. Methods: We performed genotyping of 138 patients hospitalized in the Vascular Surgery Division of the ASST-Spedali Civili di Brescia, Italy, for nontraumatic rupture of AAA. The second purpose was to observe the distribution of main nongenetic risk factors for AAA between patients with and without AATD. Results: Out of 138 patients, 22 were found with AATD: 16 MS, 1 SS, 3 MZ, and 2 with a new rare AAT variant. When compared to the general Italian population, our cohort's frequency of deficient S allele was significantly higher (7.8 vs. 2.2% respectively, P < 0.01), whereas the deficient Z allele was similar (1.1 vs. 1.3% respectively, P > 0.05). Although we found no differences in age, gender, hypertension, diabetes, and smoke habits between AAA patients with and without AATD, hyperlipidemia was significantly less frequent in patients with AATD (46.4 vs. 12.5% respectively, P < 0.05). Conclusions: In our AAA patients' cohort, the S allele frequency was higher than in the general Italian population. Our results support the hypothesis that AATD might be a risk factor for AAA.