Search

Background: Visit-to-visit blood pressure (BP) variability has been reported to be a major risk for cardiovascular events. Renin angiotensin system (RAS) gene polymorphisms are reportedly genetic risk factors for cardiovascular diseases and arterial stiffness. In this study, we aimed to reveal the relationship between visit-to-visit BP variability and RAS gene polymorphisms., Methods: Study subjects included 427 essential hypertension patients from the Non-Invasive Atherosclerotic Evaluation in Hypertension study cohort, whose BP was measured during at least six outpatient visits. We analyzed the correlation between visit-to-visit variability in systolic BP (SBP) and RAS gene polymorphisms., Results: We identified angiotensinogen M235T, angiotensin II type 1 receptor A1166C, and angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphisms. Only ACE I/D polymorphisms were correlated with variability in diastolic BP; no gene polymorphisms were correlated with variability in SBP., Conclusions: RAS gene polymorphisms, especially ACE I/D polymorphisms, might genetically influence the visit-to-visit BP variability in hypertensive patients.

To clarify the clinical utility of pulse wave velocity (PWV) and chronic kidney disease (CKD) in hypertension, we analyzed the prognostic impact of PWV and CKD on cerebrocardiovascular disease in hypertensive patients. This study consisted of 531 patients with essential hypertension (male/female=292/239, mean age=61.7±12.3, mean follow-up=7.0±3.0 years) and was performed between January 1998 and June 2004. We used questionnaires to assess stroke (n=57), cardiovascular diseases (CVDs; myocardial infarction, angina and congestive heart failure; n=44) and death (n=53) as primary end points. At baseline, we evaluated the carotid-femoral PWV (9.1±1.8 m s(-1)), the glomerular filtration rate and urinary protein excretions. We divided these subjects into those in the highest quartile of PWV and other subjects and into CKD (n=149) and non-CKD (n=458). We evaluated the prognostic influences of PWV and CKD with Kaplan-Meier analysis and Cox's proportional hazard model. PWV in CKD (9.6±1.9 m s(-1)) was higher than in non-CKD (8.8±1.6 m s(-1); P<0.0001), and creatinine was slightly decreased in the highest PWV group (1.09±0.35 mg dl(-1), P<0.0001). On the basis of Kaplan-Meier analysis, the highest PWV group (PWV>10.1 m s(-1); P=0.0003) and the CKD group (P=0.0005) showed significantly higher proportions of stroke and CVD events. In addition, the highest PWV group showed the highest percentage of stroke (P=0.0007), and the CKD group showed the highest proportion of CVD (P<00001). High PWV and CKD were independent predictors for stroke and CVD (P=0.0332) by Cox's proportional hazard model. These data suggest that increased aortic stiffness and CKD may be predictors for stroke and cardiovascular events in hypertensive patients.

The renin-angiotensin system (RAS) adversely affects stroke and cardiovascular disease; polymorphisms in genes involved in this system are associated with cardiovascular disease. The aim of the present study was to confirm the genetic risk of these polymorphisms for stroke and cardiovascular events in a cohort study of 515 hypertensive patients in Japan (follow-up period 90.6±30.2 months). The insertion/deletion (I/D) polymorphism of the gene encoding angiotensin-converting enzyme (ACE), the M235T amino acid change in angiotensinogen, and the A1166C polymorphism in angiotensin II type 1 receptor were determined by TaqMan PCR. In Kaplan-Meier analyses, the ACE I/D polymorphism was a risk factor for cerebro-cardiovascular events, especially cardiovascular events (P<0.0001), and the M235T mutation was a risk factor for cardiovascular events (P<0.0105). The cumulative rates of cerebro-cardiovascular end points for the ACE polymorphism were 10.6, 16.4 and 42.2% for the II (n=207), ID (n=244) and DD (n=64) genotype carriers, respectively (P<0.0001). Cox's proportional hazard models revealed that the ACE DD genotype was a risk factor for cerebro-cardiovascular and cardiovascular events (after adjusting for common risk factors), anti-hypertensive treatment and RAS inhibition (P<0.0001). Moreover, after adjustment for the common risk factors left ventricular hypertrophy and previous myocardial infarction/stroke, these phenomena were preserved. Thus, the DD genotype of ACE may be a genetic risk factor for cerebro-cardiovascular disease, especially cardiovascular events, in hypertensive patients in Japan.

Single-nucleotide polymorphisms (SNPs) of the β-adrenergic receptor (βADR) subtypes are related to hypertension and obesity. This hospital-based cohort study with hypertensive patients evaluated five βADR SNPs in association with cardiovascular events. The cohort included 357 hypertensive patients (male = 181; mean age = 61.5 ± 11.8 years) seen between January 1998 and June 2004. The SNPs (Ser49Gly and Arg389Gly for β(1)ADR; Gly16Arg and Glu27Gln for β(2)ADR; Trp64Arg for β(3)ADR) were identified by PCR. We used Kaplan-Meier curves to assess the prognostic effect of these SNPs on cardiovascular disease (CVD). The SNP frequencies were Ser/Ser:Ser/Gly:Gly/Gly = 243:104:10; Arg/Arg:Arg/Gly:Gly/Gly = 256:95:6; Gly/Gly:Gly/Arg:Arg/Arg = 71:201:85; Gln/Gln:Glu/Gln = 308:49; and Trp/Trp:Trp/Arg:Arg/Arg = 265:89:3. A total of 17 stroke and 15 coronary artery disease cases were recorded. By Kaplan-Meier analysis, the Ser/Ser SNP in Ser49Gly (P = 0.0398), the Glu/Gln SNP in Glu27Gln (P = 0.0390) and the Trp/Trp SNP in Trp64Arg (P = 0.0132) were associated with lower event-free CVD survival (log-rank, Mantel-Cox model). A Cox proportional hazards model revealed that only the Trp/Trp SNP (P = 0.0321) and age (P = 0.0186) were independently related to lower event-free survival for CVD, adjusted for gender, diabetes, dyslipidemia, blood pressure, body mass index, medication and hypertensive complications. Combination Kaplan-Meier analysis of these three positive SNPs indicated a higher frequency of CVD among patients with the combination of Ser/Ser in Ser49Gly of β(1), Glu/Gln in Glu27Gln of β(2) and Trp/Trp in Trp64Arg of β(3) (P = 0.0209). These three SNPs, especially the Trp64Arg SNP of β(3)ADR, might be risk factors for CVD in hypertensive patients.