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The Cochrane Database of Systematic... Apr 2017Hypertension is a chronic condition associated with an increased risk of mortality and morbidity. Renin is the enzyme responsible for converting angiotensinogen to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hypertension is a chronic condition associated with an increased risk of mortality and morbidity. Renin is the enzyme responsible for converting angiotensinogen to angiotensin I, which is then converted to angiotensin II. Renin inhibitors are a new class of drugs that decrease blood pressure (BP) by preventing the formation of both angiotensin I and angiotensin II.
OBJECTIVES
To quantify the dose-related BP lowering efficacy of renin inhibitors compared to placebo in the treatment of primary hypertension.To determine the change in BP variability, pulse pressure, and heart rate and to evaluate adverse events (mortality, non-fatal serious adverse events, total adverse events, withdrawal due to adverse effects and specific adverse events such as dry cough, diarrhoea and angioedema).
SEARCH METHODS
The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to February 2017: the Cochrane Hypertension Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 2), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. There was no restriction by language or publication status. We also searched the European Medicines Agency (EMA) for clinical study reports, the Novartis Clinical Study Results Database, bibliographic citations from retrieved references, and contacted authors of relevant papers regarding further published and unpublished work.
SELECTION CRITERIA
We included randomized, double-blinded, placebo-controlled studies evaluating BP lowering efficacy of fixed-dose monotherapy with renin inhibitor compared with placebo for a minimum duration of three to 12 weeks in adult patients with primary hypertension.
DATA COLLECTION AND ANALYSIS
This systematic review is a comprehensive update which includes four additional studies and extensive detail from nine clinical study reports (CSRs) of previously included studies obtained from EMA. The remaining three CSRs are not available.Two review authors independently assessed study eligibility and extracted data. In all cases where there was a difference between the CSR and the published report, data from the CSR was used. Dichotomous outcomes were reported as risk ratio (RR) with 95% confidence intervals (CIs) and continuous outcomes as mean difference (MD) with 95% CIs.
MAIN RESULTS
12 studies (mean duration of eight weeks) in 7439 mostly Caucasian patients (mean age 54 years) with mild-to-moderate uncomplicated hypertension were eligible for inclusion in the review. Aliskiren was the only renin inhibitor evaluated. All included studies were assessed to have high likelihood of attrition, reporting and funding bias.Aliskiren has a dose-related systolic/diastolic blood pressure (SBP/DBP) lowering effect as compared with placebo MD with 95% CI: aliskiren 75 mg (MD -2.97, 95% CI -4.76 to -1.18)/(MD -2.05, 95% CI -3.13 to -0.96) mm Hg (moderate-quality evidence), aliskiren 150 mg (MD -5.95, 95% CI -6.85 to -5.06)/ (MD -3.16, 95% CI -3.74 to -2.58) mm Hg (moderate-quality evidence), aliskiren 300 mg (MD -7.88, 95% CI -8.94 to -6.82)/ (MD -4.49, 95% CI -5.17 to -3.82) mm Hg (moderate-quality evidence), aliskiren 600 mg (MD -11.35, 95% CI -14.43 to -8.27)/ (MD -5.86, 95% CI -7.73 to -3.99) mm Hg (low-quality evidence). There was a dose-dependent decrease in blood pressure for aliskiren 75 mg, 150 mg and 300 mg. The blood pressure lowering effect of aliskiren 600 mg was not different from 300 mg (MD -0.61, 95% CI -2.78 to 1.56)/(MD -0.68, 95% CI -2.03 to 0.67). Aliskiren had no effect on blood pressure variability. Due to very limited information available regarding change in heart rate and pulse pressure, it was not possible to meta-analyze these outcomes.Mortality and non-fatal serious adverse events were not increased. This review found that in studies of eight week duration aliskiren may not increase withdrawal due to adverse events (low-quality evidence). Diarrhoea was increased in a dose-dependent manner (RR 7.00, 95% CI 2.48 to 19.72) with aliskiren 600 mg (low-quality evidence). The most frequent adverse events reported were headache, nasopharyngitis, diarrhoea, dizziness and fatigue.
AUTHORS' CONCLUSIONS
Compared to placebo, aliskiren lowered BP and this effect is dose-dependent. This magnitude of BP lowering effect is similar to that for angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). There is no difference in mortality, nonfatal serious adverse events or withdrawal due to adverse effects with short term aliskiren monotherapy. Diarrhoea was considerably increased with aliskiren 600 mg.
Topics: Amides; Antihypertensive Agents; Blood Pressure; Diarrhea; Fumarates; Humans; Middle Aged; Randomized Controlled Trials as Topic; Renin
PubMed: 28379619
DOI: 10.1002/14651858.CD007066.pub3 -
American Journal of Hypertension Feb 2023The rates of uncontrolled hypertension, along with downstream cardiovascular outcomes, has been worsening in this country. Despite the plethora of antihypertensive...
BACKGROUND
The rates of uncontrolled hypertension, along with downstream cardiovascular outcomes, has been worsening in this country. Despite the plethora of antihypertensive medications on the market, the prevalence of resistant hypertension (RH) is estimated to be 13.7%. Therefore in addition to increased clinical education and focus on lifestyle management of hypertension and medication compliance, new therapies are needed to address this rise in hypertension.
METHODS
A systematic review of the available medical literature was performed to identify emerging treatment options for RH.
RESULTS
Six different pharmacologic classes and 2 procedural interventions were identified as being appropriate for review in this paper. The pharmacologic classes to be explored are non-steroidal mineralocorticoid receptor antagonists, aminopeptidase A inhibitors, dual endothelin antagonists, aldosterone synthetase inhibitors, atrial natriuretic peptide inhibitors, and attenuators of hepatic angiotensinogen. Discussion of procedural interventions to lower blood pressure will focus on renal denervation and devices that increase carotid baroreceptor activity.
CONCLUSIONS
Promising medication and procedural interventions are being developed and studied to expand our treatment arsenal for patients with uncontrolled essential hypertension and RH.
Topics: Humans; Hypertension; Antihypertensive Agents; Blood Pressure; Kidney; Pressoreceptors
PubMed: 36201204
DOI: 10.1093/ajh/hpac111 -
Stroke Jun 2009White matter hyperintensities (WMH) are highly heritable and associated with small artery ischemic stroke, so they may be a useful trait for studying the genetics of... (Review)
Review
BACKGROUND AND PURPOSE
White matter hyperintensities (WMH) are highly heritable and associated with small artery ischemic stroke, so they may be a useful trait for studying the genetics of small vessel disease. Many studies have attempted to find associations between polymorphisms in various candidate genes and WMH. We aimed to evaluate the evidence for these associations by performing a systematic review and series of meta-analyses.
METHODS
We used a comprehensive search strategy to identify studies of the association between any genetic polymorphism and WMH. For all polymorphisms in genes studied in >2000 subjects we performed meta-analyses, calculating pooled odds ratios or standardized mean differences.
RESULTS
We identified 46 studies of polymorphisms in 19 genes in approximately 19 000 subjects. Most genes were involved in lipid metabolism, control of vascular tone, or blood pressure regulation. Polymorphisms in the apolipoprotein E, angiotensin-converting enzyme, methylenetetrahydrofolate reductase, and angiotensinogen genes had been studied in >2000 subjects and were evaluated by meta-analysis. There was no evidence for an association between apolipoprotein E (epsilon 4+/-), methylenetetrahydrofolate reductase (677 cytosine/thymine polymorphism [C/T]), or angiotensinogen (Met235Thr) and WMH. For the angiotensin-converting enzyme insertion/deletion polymorphism (I/D) there appeared to be a significant association (OR, 1.95; 95% CI, 1.09-3.48), but this may be partly attributable to the small study (mainly publication) and other biases.
CONCLUSIONS
No genetic polymorphism has yet shown convincing evidence for an association with WMH. Much larger studies will be needed to detect and confirm genetic associations with this promising trait in the era of genome-wide association studies.
Topics: Apolipoproteins E; Brain; Brain Ischemia; Gene Frequency; Genotype; Humans; Methylenetetrahydrofolate Reductase (NADPH2); O(6)-Methylguanine-DNA Methyltransferase; Odds Ratio; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Stroke
PubMed: 19407234
DOI: 10.1161/STROKEAHA.108.542050 -
The Cochrane Database of Systematic... Oct 2008Hypertension is a chronic condition associated with an increased risk of mortality and morbidity. The renin-angiotensin-aldosterone system is an important target site... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hypertension is a chronic condition associated with an increased risk of mortality and morbidity. The renin-angiotensin-aldosterone system is an important target site for five antihypertensive drug classes: beta blockers, renin inhibitors, ACE inhibitors, angiotensin receptor blockers (ARBs) and aldosterone inhibitors. Renin is the enzyme responsible for converting angiotensinogen to angiotensin I, which is then converted to angiotensin II. Renin inhibitors prevent the formation of both angiotensin I and angiotensin II . Renin inhibitors do not affect kinin metabolism and may produce fewer adverse effects than ACE inhibitors such as dry cough or angioedema.
OBJECTIVES
To quantify the dose-related blood pressure lowering efficacy of renin inhibitors versus placebo in the treatment of primary hypertension.
SEARCH STRATEGY
We searched the following databases for randomised, double blind, placebo-controlled trials of renin inhibitors: Medline (1966-March 2008), EMBASE (1988-March 2008), Cochrane CENTRAL, and bibliographic citations from retrieved references. No language restrictions were applied.
SELECTION CRITERIA
Study design had to meet the following criteria: double-blinded, placebo-controlled; random allocation to a specific dose of renin inhibitor group and parallel placebo group; duration of follow-up of at least three weeks.
DATA COLLECTION AND ANALYSIS
Two reviewers independently extracted data and assessed trial quality using risk of bias tables. Disagreements were resolved by discussion or a third reviewer. Data synthesis and analyses were done using the Cochrane Review Manager software, RevMan 5. Data for continuous variables were combined using a weighted mean difference method. Dichotomous variables were analysed using relative risk.
MAIN RESULTS
Six trials (N=3694) met the inclusion criteria for this review. Aliskiren was the only renin inhibitor studied in these studies. The meta-analysis shows that aliskiren has a dose-related both systolic/diastolic blood pressure lowering effect as compared to placebo: aliskiren 75 mg -2.9/-2.3 mmHg, aliskiren 150 mg -5.5/-3.0 mmHg, aliskiren 300 mg -8.7/-5.0, aliskiren 600 mg -11.4/-6.6 mmHg. Aliskiren 300 mg significantly lowered both SBP and DBP as compared to aliskiren 150 mg (SBP:-2.97 (95% CI -3.99, -1.95) and DBP: -1.66 (95% CI -2.32, -1.0). Aliskiren has no effect on blood pressure variability. No data was available to assess the effect of aliskiren on heart rate and pulse pressure. This review found weak evidence that with short- term use, aliskiren does not increase withdrawals due to adverse effects as compared to placebo.
AUTHORS' CONCLUSIONS
Aliskiren has a dose-related blood pressure lowering effect better than placebo. This effect is similar to that determined for ACE inhibitors and ARBs.
Topics: Amides; Antihypertensive Agents; Blood Pressure; Fumarates; Humans; Hypertension; Randomized Controlled Trials as Topic; Renin
PubMed: 18843743
DOI: 10.1002/14651858.CD007066.pub2 -
Journal of Science and Medicine in Sport May 2016To meta-analyze candidate gene association studies on the change in blood pressure beyond the immediate post-exercise phase after versus before aerobic exercise. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To meta-analyze candidate gene association studies on the change in blood pressure beyond the immediate post-exercise phase after versus before aerobic exercise.
DESIGN
Meta-analysis.
METHODS
A systematic search was conducted. Studies retrieved included acute (short-term or postexercise hypotension) or chronic (long-term or training) aerobic exercise interventions; and blood pressure measured before and after aerobic exercise training, or before and after exercise or control under ambulatory conditions by genotype. Effect sizes were determined for genotype and adjusted for sample features.
RESULTS
Qualifying studies (k=17, n=3524) on average included middle-aged, overweight men (44.2%) and women (55.8%) with prehypertension (134.9±11.7/78.6±9.5mmHg). Training interventions (k=12) were performed at 60.4±12.9% of maximum oxygen consumption (VO2max) for 41.9±12.5minsession(-1), 3.6±1.2daysweek(-1) for 15.7±7.6week; and post-exercise hypotension interventions (k=5) were performed at 53.5±14.4% VO2max for 38.5±5.4minsession(-1). Sample characteristics explained 54.2-59.0% of the variability in the blood pressure change after versus before acute exercise or control under ambulatory conditions, and 57.4-67.1% of the variability in the blood pressure change after versus before training (p<0.001). Only angiotensinogen M235T (rs699) associated with the change in diastolic blood pressure after versus before training (R(2)=0.1%, p=0.05), but this association did not remain statistically significant after adjustment for multiple comparisons.
CONCLUSIONS
Sample characteristics explained most of the variability in the change of BP beyond the immediate post-exercise phase after versus before acute and chronic aerobic exercise. Angiotensinogen M235T (rs699) was the only genetic variant that associated with the change in diastolic blood pressure after versus before training, accounting for <1% of the variance.
Topics: Adult; Blood Pressure; Exercise; Female; Humans; Male; Middle Aged; Regression Analysis
PubMed: 26122461
DOI: 10.1016/j.jsams.2015.05.009 -
Revista Brasileira de Ginecologia E... Jul 2022To describe the effects of combined oral contraceptives (COC) on the renin-angiotensin-aldosterone system (RAAS).
OBJECTIVE
To describe the effects of combined oral contraceptives (COC) on the renin-angiotensin-aldosterone system (RAAS).
DATA SOURCES
This is a systematic review according to the criteria of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), registered in PROSPERO under the ID: CRD42020200019. Searches were performed between August 2020 and December 2021, in the following databases: Medline via Pubmed, Cochrane Central Library, Scientific Electronic Library Online, and Latin American and Caribbean Literature in Health Sciences via Virtual Health Library. The effects of the combined oral contraceptive on plasma renin activity values, plasma renin values, angiotensinogen values- also known as plasma renin substrate- angiotensin, and/or aldosterone values.
STUDY SELECTION
A total of 877 studies were selected and, of these, 10 articles met the eligibility criteria and were included in this review.
DATA COLLECTION
Data were combined through qualitative synthesis and included in a spreadsheet previously prepared by the authors.
DATA SYNTHESIS
The collected samples ranged from 18 to 137 participants, totaling 501 women aged between 18 and 49 years throughout all studies. The studies showed increased activity of plasma renin, plasma renin substrate, angiotensin II, and aldosterone in this population.
CONCLUSION
The findings of this study suggest that the COC promotes greater activation of the RAAS. Supporting the idea that its use is related to an increased risk of cardiovascular events, including systemic arterial hypertension.
Topics: Adolescent; Adult; Aldosterone; Angiotensinogen; Contraceptives, Oral, Combined; Female; Humans; Middle Aged; Renin; Renin-Angiotensin System; Young Adult
PubMed: 35724684
DOI: 10.1055/s-0042-1745790 -
Cardiology Journal 2022In this recent publication review the authors aimed to collect evidence of impact of nonsynonymous single nucleotide polymorphisms (nsSNP) in the...
In this recent publication review the authors aimed to collect evidence of impact of nonsynonymous single nucleotide polymorphisms (nsSNP) in the renin-angiotensin-aldosterone system on patients' phenotype not only regarding arterial hypertension and its complications, but also the impact on other diseases of interest outside the field of cardiovascular medicine. PubMed database records published between 2017-2020 were searched and all positive case-control studies or positive studies with human DNA were selected. The search identified 104 articles, of which 22 were included on the basis of the inclusion criteria. This paper presents the impact of 44 nsSNPs in panels for genes of renin, angiotensinogen, angiotensin-converting enzyme, angiotensin receptor and aldosterone on the clinical picture of investigated cohorts or on the peptide-protein interactions as consequence of nsSNPs. Genetic variability in nsSNPs of the RAAS is involved in the pathogenesis of arterial hypertension and its complications, and surprisingly also in the pathogenesis of conditions not associated with elevated blood pressure, like neoplasms or inflammatory diseases.
Topics: Humans; Renin-Angiotensin System; Polymorphism, Single Nucleotide; Renin; Aldosterone; Hypertension
PubMed: 34060646
DOI: 10.5603/CJ.a2021.0055 -
American Journal of Obstetrics and... Feb 2022There has been increasing research momentum to identify new therapeutic agents for the prevention or treatment of preeclampsia, drugs that can affect the underlying...
There has been increasing research momentum to identify new therapeutic agents for the prevention or treatment of preeclampsia, drugs that can affect the underlying disease pathophysiology. Molecular targets of candidate treatments include oxidative stress, antiangiogenic factors, and the angiotensin, nitric oxide, and proinflammatory pathways. The proposed treatments undergoing preclinical and clinical trial evaluation are thought to act on placental or endothelial disease or both. Most have adopted the pragmatic strategy of repurposing drugs. Of all the therapeutic agents proposed, pravastatin has received the most interest. There are preclinical studies showing that it has pleiotropic actions that favorably impact on multiple molecular targets and can resolve a preeclampsia phenotype in many animal models. An early phase clinical trial suggests that it may have therapeutic activity. Several large prevention trials are planned or ongoing and, when completed, could definitively address whether pravastatin can prevent preeclampsia. Proton-pump inhibitors, metformin, and sulfasalazine are other drugs with preclinical evidence of multiple molecular actions that could resolve the pathophysiology of preeclampsia. These agents are also currently being evaluated in clinical trials. There have been many recent preclinical studies identifying the potential of numerous natural compounds to treat preeclampsia, such as plant extracts and micronutrients that have potent anti-inflammatory or antioxidant activity. Recent preclinical studies have also proposed novel molecular-targeted strategies, such as monoclonal antibodies targeting tumor necrosis factor alpha, placental growth factor, and short interfering RNA technology, to silence the gene expression of soluble fms-like tyrosine kinase-1 or angiotensinogen. Other treatment approaches that have transitioned to human trials (ranging from single-arm to phase III trials that have been completed or are ongoing) include folic acid, nitric oxide donors (such as L-arginine), recombinant antithrombin III, digoxin immune antigen-binding fragment, and melatonin. There have been case series showing the removal of circulating soluble fms-like tyrosine kinase-1 may help stabilize the disease and prolong pregnancy. Interestingly, there are case reports suggesting that monoclonal antibody eculizumab (complement inhibitor) may have therapeutic potential. If new agents are discovered that are proven to be effective in preventing or treating preeclampsia, the potential to improve global maternal and perinatal health will be significant.
Topics: Antibodies, Monoclonal; Antioxidants; Antithrombin III; Biological Products; Blood Component Removal; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Metformin; Micronutrients; Placenta Growth Factor; Plant Extracts; Pravastatin; Pre-Eclampsia; Pregnancy; Proton Pump Inhibitors; RNA, Small Interfering; Recombinant Proteins; Sulfasalazine; Vascular Endothelial Growth Factor Receptor-1
PubMed: 32946849
DOI: 10.1016/j.ajog.2020.09.014 -
PloS One 2024Due to the inconsistent findings from various studies, the role of gene polymorphisms in the renin-angiotensin system in influencing the development of cardiomyopathy... (Meta-Analysis)
Meta-Analysis
Due to the inconsistent findings from various studies, the role of gene polymorphisms in the renin-angiotensin system in influencing the development of cardiomyopathy remains unclear. In this study, we conducted a systematic review and meta-analysis to summarize the findings regarding the impact of angiotensin converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T, and angiotensin II Type 1 receptor (AGTR1) A1166C gene polymorphisms in patients with cardiomyopathy. We performed a comprehensive search of several electronic databases, including PubMed, Embase, the Cochrane Library, and Web of Science, covering articles published from the time of database creation to April 17, 2023. Studies on the assessment of genetic polymorphisms in genes related to the renin-angiotensin system in relation to cardiomyopathy were included. The primary outcome was cardiomyopathy. Risk of bias was assessed using the Newcastle-Ottawa Scale scale. The meta-analysis includes 19 studies with 4,052 cases and 5,592 controls. The ACE I/D polymorphisms were found to be associated with cardiomyopathy (allelic model D vs I: OR = 1.29, 95CI% = 1.08-1.52; dominant model DD+ID vs II: OR = 1.43, 95CI% = 1.01-2.02; recessive model DD vs ID+II: OR = 0.79, 95CI% = 0.64-0.98). AGT M235T polymorphism and cardiomyopathy were not significantly correlated (allelic model T vs M: OR = 1.26, 95CI% = 0.96-1.66; dominant model TT+MT vs MM: OR = 1.30, 95CI% = 0.98-1.73; recessive model TT vs MT+MM: OR = 0.63, 95CI% = 0.37-1.07). AGTR1 polymorphism and cardiomyopathy were not significantly associated under allelic model A vs C (OR = 0.69, 95CI% = 0.46-1.03) and recessive model AA vs CA+CC (OR = 0.89, 95CI% = 0.34-2.30), but under the dominant model AA+CA vs CC (OR = 0.51, 95CI% = 0.38-0.68). The current meta-analysis reveals that polymorphisms in ACE I/D may be a genetic risk factor for cardiomyopathy. There is an association between AGTR1 gene polymorphisms and risk of cardiomyopathy under the specific model.
Topics: Humans; Renin-Angiotensin System; Risk Factors; Polymorphism, Genetic; Peptidyl-Dipeptidase A; Angiotensinogen; Cardiomyopathies; Receptor, Angiotensin, Type 1
PubMed: 38166133
DOI: 10.1371/journal.pone.0295626 -
Journal of Cardiovascular Risk 1997Variants of the human genes coding for renin, angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and the angiotensin II type-I receptor (AT1R) are inconsistently... (Review)
Review
BACKGROUND
Variants of the human genes coding for renin, angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and the angiotensin II type-I receptor (AT1R) are inconsistently associated with cardiovascular-renal disease, possibly because of genetic differences in the background populations.
METHODS
This systematic review of the literature investigated genetic variation in the renin system according to race, sex and age. Across studies with relevant information, multivariate analyses also accounted for the methods of genotyping and the enrollment of subjects as controls, cases or groups studied cross-sectionally.
RESULTS
The 185 reviewed reports included 64978 subjects. In five studies (n=989) on the renin gene, the Hind III and Taq I polymorphisms varied with the groups' average age, whereas the Bg I, Bg II and Hind III but not Taq I sites differed according to race. Among 135 studies (n=44697) on the deletion/insertion (D/I) polymorphism of the ACE gene, the frequency of the D allele was 54.0%. Its prevalence was not related to sex and black race, was 49.9% lower in Asians, 10.0% lower in studies relying on I-specific primers, 4.9% higher for each 25-year increment in the average age of the groups studied, and 16.7% higher in cases than controls. Among 12 studies (n=4952) on the T174-->M variant of the AGT gene, the M174 frequency was 11.0%, did not vary according to sex and enrollment group, was 56.7% lower in blacks and 39.5% lower for each 25-year increase in the groups' mean age. Across 44 studies (n=16713) on the M235-->T substitution in the AGT gene, the T235 prevalence was 51.6%. Its frequency was not related to sex and the method of genotyping, tended to be 7.5% lower for each 25-year increase in average age, was from 4.6 to 6.6 times higher in nonwhites than whites and 13.2% higher in cases than controls. Among 13 studies (n=4332) on the A1166-->C variant of the AT1R gene, the C1166 allelic frequency was 25.7%. Its prevalence was independent of the enrollment group, 77.4% lower in Asians, and nearly doubled for each 25-year increment in age.
CONCLUSION
With adjustments applied for the subjects' enrollment group and the methods of genotyping, genetic polymorphism in the renin system varies according to race and age, but not sex. One possible application of the present results is to provide allelic and genotypic frequencies, which could be used to assess power, to perform sample size calculations, or to predict selection bias in future studies.
Topics: Age Factors; Analysis of Variance; Cardiovascular Diseases; Case-Control Studies; Cross-Sectional Studies; Female; Gene Frequency; Genetic Variation; Genotype; Humans; Kidney Diseases; Male; Racial Groups; Renin-Angiotensin System; Risk Factors; Sex Factors
PubMed: 9865673
DOI: No ID Found