Association Between Genetic Variation in Blood Pressure and Increased Lifetime Risk of Peripheral Artery Disease.
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ABSTRACT:
SUBMITTER: Levin MG
PROVIDER: S-EPMC8159880 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
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Association Between Genetic Variation in Blood Pressure and Increased Lifetime Risk of Peripheral Artery Disease.
Levin Michael G MG Klarin Derek D Walker Venexia M VM Gill Dipender D Lynch Julie J Hellwege Jacklyn N JN Keaton Jacob M JM Lee Kyung M KM Assimes Themistocles L TL Natarajan Pradeep P Hung Adriana M AM Edwards Todd L TL Rader Daniel J DJ Gaziano J Michael JM Davies Neil M NM Tsao Philip S PS Chang Kyong-Mi KM Voight Benjamin F BF Damrauer Scott M SM
Arteriosclerosis, thrombosis, and vascular biology 20210415 6
[Figure: see text]. ...[more]
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Project description:BackgroundCurrent guidelines recommend treating hypertension in patients with peripheral artery disease (PAD) to reduce the risk of cardiac events and stroke, but the effect of reducing blood pressure on lower extremity PAD events is largely unknown. We investigated the association of blood pressure with lower extremity PAD events using data from the ALLHAT trial (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).MethodsALLHAT investigated the effect of different antihypertensive medication classes (chlorthalidone, amlodipine, lisinopril, or doxazosin) on cardiovascular events. With the use of these data, the primary outcome in our analysis was time to first lower extremity PAD event, defined as PAD-related hospitalization, procedures, medical treatment, or PAD-related death. Given the availability of longitudinal standardized blood pressure measurements, we analyzed systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure as time-varying categorical variables (reference categories 120-129 mm Hg for SBP, 70-79 mm Hg for DBP, and 45-54 mm Hg for pulse pressure) in separate models. We used extended Cox regression with death as a competing risk to calculate the association of each blood pressure component with PAD events, and report the results as subdistribution hazard ratios and 95% CIs.ResultsThe present analysis included 33 357 patients with an average age of 67.4 years, 53.1% men, 59.7% white race, and 36.2% with diabetes mellitus. The median baseline blood pressure was 146/84 mm Hg. Participants were followed for a median of 4.3 (interquartile range, 3.6-5.3) years, during which time 1489 (4.5%) had a lower extremity PAD event, and 4148 (12.4%) died. In models adjusted for demographic and clinical characteristics, SBP <120 mm Hg was associated with a 26% (CI, 5%-52%; P=0.015) higher hazard and SBP≥160 mm Hg was associated with a 21% (CI, 0%-48%; P=0.050) higher hazard for a PAD event, in comparison with SBP 120 to 129 mm Hg. In contrast, lower, but not higher, DBP was associated with a higher hazard of PAD events: for DBP <60 mm Hg (hazard ratio, 1.72; CI, 1.38-2.16). Pulse pressure had a U-shaped association with PAD events.ConclusionsIn this reanalysis of data from ALLHAT, we found a higher rate of lower extremity PAD events with higher and lower SBP and pulse pressure and with lower DBP. Given the recent revised blood pressure guidelines advocating lower SBP targets for overall cardiovascular risk reduction, further refinement of optimal blood pressure targets specific to PAD is needed.Clinical trial registrationURL: https://www.clinicaltrials.gov . Unique identifier: NCT00000542.
| S-EPMC6202170 | biostudies-literature
Project description:Background Hypertension is an important risk factor for cardiovascular events in patients with peripheral artery disease; however, optimal blood pressure targets for these patients are poorly defined. This study investigated the association between systolic blood pressure ( SBP ) and cardiovascular events in a prospectively recruited patient cohort with peripheral artery disease. Methods and Results A total of 2773 patients were included and were grouped according to SBP at recruitment (≤120 mm Hg, n=604; 121-140 mm Hg, n=1065; and >140 mm Hg, n=1104). Adjusted Cox proportional hazards analyses suggested that patients with SBP ≤120 mm Hg were at greater risk of having a major cardiovascular event (myocardial infarction, stroke, or cardiovascular death) than patients with SBP of 121-140 mm Hg (adjusted hazard ratio, 1.36; 95% CI, 1.08-1.72; P=0.009). Patients with SBP >140 mm Hg had an adjusted hazard ratio of 1.23 (95% CI, 1.00-1.51; P=0.051) of major cardiovascular events compared with patients with SBP of 121-140 mm Hg. These findings were similar in sensitivity analyses only including patients receiving antihypertensive medications or focused on patients with a minimum of 3 months of follow-up. Conclusions This cohort study suggests that patients with peripheral artery disease and SBP ≤120 mm Hg are at increased risk of major cardiovascular events. The findings suggest caution in intensive SBP lowering in this patient group.
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Project description:[Figure: see text].
| S-EPMC8119358 | biostudies-literature
Project description:IntroductionGenetic variation may play explain some of the disparity in prevalence and control of hypertension across Sub-Saharan Africa. However, there have been very few studies to characterize genetic variation of blood pressure traits.AimTo determine whether a set of blood pressure-associated genetic loci can be replicated among samples East African samples.MethodsTwenty-seven blood pressures (BP)-related single nucleotide polymorphisms (SNPs) were genotyped among 2881 samples from participants in the Medical Education Partnership Initiative for Cardiovascular Disease (MEPI-CVD) survey. Associations with known BP variants were evaluated for systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) as continuous variables and for hypertension (HTN) as a binary variable.ResultsEleven SNPS were associated with at least 1 BP trait (P < .05). Four SNPs; rs2004776, rs7726475, rs11837544 and rs2681492, whose nearest genes are AGT, NPR3/SUB1, PLXNC1 and ATP2B1, respectively, were associated with SBP. Six SNPs, rs2004776, rs11977526, rs11191548, rs381815, rs2681492 and rs1327235, close to AGT, IGFBP3, CYP17A1, PLEKHA7, ATP2B1 and JAG, respectively, were associated with DBP while 2 SNPs located within AGT and IGFBP-3 genes associated with HTN. For PP, 4 variants rs1458038, rs11725861, rs7726475 and rs11953630 whose corresponding genes are FGF5, CHIC2, SUB1/NPR3 and EBF1 reached significance (P < .05). Eight SNPs were replicated in the same effect direction as the parent studies. Risk scores defined using published effect sizes were significantly associated with both SBP (P = .0026) and DBP (P = .0214).ConclusionThe replication of multiple BP variants among East Africans suggests that these variants may have universal effects across ethnic populations.
| S-EPMC6190611 | biostudies-literature
Project description:In hemodialysis patients, blood pressure variability (BPV) is associated with cardiovascular events and all-cause mortality. However, previous research has predominantly concentrated on the predialysis BPV. In contrast, intradialytic BPV, reflecting the cardiovascular regulatory function during the process of rapid clearance of volume overload, holds greater relevance to the prognosis of patients. In this study, a latent category trajectory model was used to identify the patterns of intradialytic BPV and analyze the association between intradialytic BPV and the cardio-cerebrovascular events and other clinical outcomes. We found the variation of intradialytic systolic blood pressure (SBP) was associated with the risk of cardio-cerebrovascular events in hemodialysis patients. Patients in "SBP Class 4" and "SBP Class 3" subgroups were associated with the occurrence of cardio-cerebrovascular events and the number of cardio-cerebrovascular event hospitalizations during the follow-up period. This indicates that the variation pattern of intradialytic SBP results from the comprehensive action of various BP regulatory mechanisms in the body, which can reflect the level of cardiovascular regulatory function in hemodialysis patients and serve as a predictor of recent adverse cardio-cerebrovascular events.
| S-EPMC11774084 | biostudies-literature
Project description:The association between blood pressure and intracranial artery stenosis (ICAS) in different age groups has not been elucidated. Using data from the "China Hypertension Survey," we conducted a cross-sectional analysis of the association between blood pressure parameters and ICAS. In this study, participants older than 35 years were selected by stratified, multistage random sampling. Blood pressure was measured repeatedly at rest, and ICAS was assessed by transcranial doppler ultrasound. Binary logistic regression analysis was used to demonstrate the association between different blood pressure indicators and ICAS. Of the 3640 participants included (mean age 63 ± 13 years old, 57.8% female), systolic blood pressure (SBP) and pulse pressure (PP) were associated with ICAS in the general population; the multivariable adjusted odds ratio (OR) and corresponding 95% confidence interval (95% CI) of ICAS and multivessel stenosis were 1.32 (1.21, 1.45) and 1.29 (1.14, 1.46) per standard deviation (SD) increase in SBP and 1.44 (1.30, 1.59) and 1.52 (1.33, 1.74) for PP, respectively. Further analysis of this association in different age groups revealed inconsistent results between SBP and ICAS. Prehypertension (120 ≤ SBP < 140) could predict ICAS in the older group but not in the younger group, and the positive association between SBP and multivessel stenosis disappeared in the younger age group (P > .05 in all SBP subgroups). In conclusion, SBP and PP could not only identify ICAS in the middle-aged and elderly population but could also provide some information about ICAS burden; however, these associations need to be interpreted differentially based on age subgroup.
| S-EPMC8029804 | biostudies-literature
Project description:Elevated blood pressure (BP) is a major risk factor for cardiovascular disease. Several studies have noted a consistent maternal effect on BP; consequently, mitochondrial DNA variation has become an additional target of investigation of the missing BP heritability. Analyses of common mitochondrial DNA polymorphisms, however, have not found evidence of association with hypertension. To explore associations of uncommon (frequency>5%) mitochon drial DNA variants with BP, we identified uncommon/rare variants through sequencing the entire mitochondrial genome in 32 unrelated individuals with extreme-high BP in the Framingham Heart Study and genotyped 40 mitochondrial single nucleotide polymorphisms in 7219 Framingham Heart Study participants. The nonsynonymous mitochondrial single nucleotide polymorphism 5913G>A (Asp4Asn) in the cytochrome c oxidase subunit 1 of respiratory complex IV demonstrated significant associations with BP and fasting blood glucose (FBG) levels. Individuals with the rare 5913A allele had, on average, 7-mm Hg higher systolic BP at baseline (Pempirical=0.05) and 17-mg/dL higher mean FBG over 25 years of follow-up (Pempirical=0.009). Significant associations with FBG levels were also detected for nonsynonymous mitochondrial single nucleotide polymorphism 3316G>A (Ala4Thr) in the NADH dehydrogenase subunit 1 of complex I. On average, individuals with rare allele 3316A had 17- and 25-mg/dL higher FBG at baseline (Pempirical=0.01) and over 25 years of follow-up (Pempirical=0.007). Our findings provide the first evidence of putative association of variants in the mitochondrial genome with systolic BP and FBG in the general population. Replication in independent samples, however, is needed to confirm these putative associations.
| S-EPMC3753106 | biostudies-literature
Project description:Spot central and peripheral blood pressure are predictors for future hypertension, but the associations between central or peripheral systolic blood pressure (SBP) changes and new-onset hypertension are unclear. Annual changes in central and peripheral SBP over a mean interval of 2.36 years were calculated for 815 Chinese community residents without cardiovascular disease and hypertension at the first two visits, with the formula: ([2nd SBP-1st SBP]/1st SBP) × 100%/time interval (years). The independent and joint associations of these SBP changes with new-onset hypertension at the third visit were assessed with multivariable logistic regression models. During a mean follow-up interval of 4.37 years since the second visit, 171 new cases of hypertension were observed. Central and peripheral SBP changes were significantly associated with new-onset hypertension (central SBP change rate: odds ratio [OR]: 1.19 [95% confidence intervals (CI) 1.13, 1.26]; peripheral SBP change rate: OR: 1.25 [95% CI 1.17, 1.33]), even after adjusting for each other. Compared to the group with neither SBP increased, the group with both SBPs increased showed a significantly higher risk of new-onset hypertension (OR: 4.52 [95% CI 2.54, 8.04]). The model including both SBP changes had a higher area under the curve (AUC) for predicting hypertension in receiver operating characteristic (ROC) analyses than those with either change alone. Central and peripheral SBP changes are independently and jointly associated with new-onset hypertension. It is recommended to regularly monitor both central and peripheral blood pressures.
| S-EPMC11654846 | biostudies-literature
Project description:Objective- Arterial stiffness index (ASI) is independently associated with blood pressure (BP) and coronary artery disease (CAD) epidemiologically. However, it is unknown whether these associations represent causal relationships. Here, we assess whether genetic predisposition to increased ASI is associated with elevated BP and CAD risk. Approach and Results- We first performed a large-scale epidemiological association of finger photoplethysmography-derived ASI in the UK Biobank, finding significant associations with systolic BP (β=0.55 mm Hg; [95% CI, 0.45-0.65]; P=5.77×10-24; N=137 858), diastolic BP (β=1.05 mm Hg; [95% CI, 0.99-1.11]; P=7.27×10-272; N=137 862), and incident CAD (hazard ratio, 1.08; [95% CI, 1.04-1.11]; P=1.5×10-6; N=3692 cases, 126 615 controls) in multivariable models. We then performed an ASI genome-wide association study analysis in 131 686 participants from the UK Biobank. Across participants not in the ASI genome-wide association study, a 6-variant ASI polygenic risk score was calculated. Each SD increase in genetic ASI was associated with systolic BP (β=4.63 mm Hg; [95% CI, 2.1-7.2]; P=3.37×10-4; N=208 897), and diastolic BP (β=2.61 mm Hg; [95% CI, 1.2-4.0]; P=2.85×10-4; N=208 897); however, no association was observed with incident CAD (hazard ratio, 1.12; [95% CI, 0.55-2.3]; P=0.75; N=223 061; 7534 cases). The lack of CAD association observed was replicated among 184 305 participants (60 810 cases) from the CARDIOGRAMplusC4D (Coronary Artery Disease Genetics Consortium; odds ratio, 0.56; [95% CI, 0.26-1.24]; P=0.15). Conclusions- Our data support the conclusion that finger photoplethysmography-derived ASI is an independent, genetically causal risk factor for BP, but do not support the notion that ASI is a suitable surrogate for CAD risk.
| S-EPMC6531323 | biostudies-literature
Project description:Several observational studies have revealed that immune-mediated inflammatory diseases (IMIDs) are associated with an increased risk of peripheral artery disease (PAD). However, the causal association remains to be determined. To corroborate previous research, we conducted Mendelian randomization (MR) analysis with the aim of clarifying the associations of various IMIDs with PAD. two-sample MR analysis was conducted to investigate the potential causal association between eight common IMIDs (including rheumatoid arthritis (RA), Crohn's disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE), ankylosing spondylitis(AS), psoriasis(PSO), multiple sclerosis(MS), and hashimoto thyroiditis(HT)) and PAD. Genome-wide association study (GWAS) was used to identify genetic variants associated with IMIDs and PAD. We employed the inverse variance weighted (IVW) method as the primary method to verify the causal relationship between exposures (IMIDs) and outcomes (PAD). In addition, heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis were performed to evaluate the robustness of the MR results. The IVW model yielded evidence of a positive association between RA and PAD (OR = 1.059, 95% CI: 1.026-1.094, p<0.001), which was consistent with the results obtained from MR-Egger regression and weighted median analyses, indicating that the results of MR analysis were reliable. However, no statistically significant associations were observed between other IMIDs, including UC, CD, SLE, AS, PSO, MS, and HT, and PAD. Our analysis supported the causal association of RA with increased risks of PAD. Strengthening screening and prevention of PAD is of great significance in reducing the risk of PAD in populations with RA.
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