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  • Ovid Technologies (Wolters Kluwer Health)  (16)
  • 1
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    Online Resource
    Blood Pressure Targets and Absolute Cardiovascular Risk
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Hypertension Vol. 66, No. 2 ( 2015-08), p. 280-285
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 66, No. 2 ( 2015-08), p. 280-285
    Abstract: In the Eighth Joint National Committee guideline on hypertension, the threshold for the initiation of blood pressure–lowering treatment for elderly adults (≥60 years) without chronic kidney disease or diabetes mellitus was raised from 140/90 mm Hg to 150/90 mm Hg. However, the committee was not unanimous in this decision, particularly because a large proportion of adults ≥60 years may be at high cardiovascular risk. On the basis of Eighth Joint National Committee guideline, we sought to determine the absolute 10-year risk of cardiovascular disease among these adults through analyzing the National Health and Nutrition Examination Survey (2005–2012). The primary outcome measure was the proportion of adults who were at ≥20% predicted absolute cardiovascular risk and above goals for the Seventh Joint National Committee guideline but reclassified as at target under the Eighth Joint National Committee guideline (reclassified). The Framingham General Cardiovascular Disease Risk Score was used. From 2005 to 2012, the surveys included 12 963 adults aged 30 to 74 years with blood pressure measurements, of which 914 were reclassified based on the guideline. Among individuals reclassified as not in need of additional treatment, the proportion of adults 60 to 74 years without chronic kidney disease or diabetes mellitus at ≥20% absolute risk was 44.8%. This corresponds to 0.8 million adults. The proportion at high cardiovascular risk remained sizable among adults who were not receiving blood pressure–lowering treatment. Taken together, a sizable proportion of reclassified adults 60 to 74 years without chronic kidney disease or diabetes mellitus was at ≥20% absolute cardiovascular risk.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.114.04997
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 2094210-2
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  • 2
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    The Epidemiology of Blood Pressure and Its Worldwide Management
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Circulation Research Vol. 116, No. 6 ( 2015-03-13), p. 925-936
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 116, No. 6 ( 2015-03-13), p. 925-936
    Abstract: Despite the vast amount of evidence on the benefits of blood pressure lowering accumulated to date, elevated blood pressure is still the leading risk factor for disease and disability worldwide. The purpose of this review is to summarize the epidemiological evidence underpinning the association between blood pressure and a range of conditions. This review focuses on the association between systolic and diastolic blood pressures and the risk of cardiovascular and renal disease. Evidence for and against the existence of a J-shaped curve association between blood pressure and cardiovascular risk, and differences in the predictive power of systolic, diastolic, and pulse pressure, are described. In addition, global and regional trends in blood pressure levels and management of hypertension are reviewed.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/CIRCRESAHA.116.304723
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 1467838-X
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  • 3
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    Genome-Wide Polygenic Score and Cardiovascular Outcomes With Evacetrapib in Patients With High-Risk Vascular Disease : A Nested Case-Control Study
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation: Genomic and Precision Medicine Vol. 13, No. 1 ( 2020-02)
    Details
    In: Circulation: Genomic and Precision Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 13, No. 1 ( 2020-02)
    Type of Medium: Online Resource
    ISSN: 2574-8300
    URL: Article
    DOI: 10.1161/CIRCGEN.119.002767
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2927603-2
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  • 4
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    Associations of Epicardial, Abdominal, and Overall Adiposity With Atrial Fibrillation
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Circulation: Arrhythmia and Electrophysiology Vol. 9, No. 12 ( 2016-12)
    Details
    In: Circulation: Arrhythmia and Electrophysiology, Ovid Technologies (Wolters Kluwer Health), Vol. 9, No. 12 ( 2016-12)
    Abstract: Although adiposity is increasingly recognized as a risk factor for atrial fibrillation (AF), the importance of epicardial fat compared with other adipose tissue depots remains uncertain. We sought to characterize and compare the associations of AF with epicardial fat and measures of abdominal and overall adiposity. Methods and Results— We conducted a meta-analysis of 63 observational studies including 352 275 individuals, comparing AF risk for 1-SD increases in epicardial fat, waist circumference, waist/hip ratio, and body mass index. A 1-SD higher epicardial fat volume was associated with a 2.6-fold higher odds of AF (odds ratio, 2.61; 95% confidence interval [CI], 1.89–3.60), 2.1-fold higher odds of paroxysmal AF (odds ratio, 2.14; 95% CI, 1.45–3.16) and, 5.4-fold higher odds of persistent AF (odds ratio, 5.43; 95% CI, 3.24–9.12) compared with sinus rhythm. Likewise, a 1-SD higher epicardial fat volume was associated with 2.2-fold higher odds of persistent compared with paroxysmal AF (odds ratio, 2.19; 95% CI, 1.66–2.88). Similar associations existed for postablation, postoperative, and postcardioversion AF. In contrast, associations of abdominal and overall adiposity with AF were less extreme, with relative risks per 1-SD higher values of 1.32 (95% CI, 1.25–1.41) for waist circumference, 1.11 (95% CI, 1.08–1.14) for waist/hip ratio, and 1.22 (95% CI, 1.17–1.27) for body mass index. Conclusions— Strong and graded associations were observed between increasing epicardial fat and AF. Moreover, the strength of associations of AF with epicardial fat is greater than for measures of abdominal or overall adiposity. Further studies are needed to assess the mechanisms and clinical relevance of epicardial fat.
    Type of Medium: Online Resource
    ISSN: 1941-3149 , 1941-3084
    URL: Article
    DOI: 10.1161/CIRCEP.116.004378
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 2425487-3
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  • 5
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    Protein-Truncating Variants at the Cholesteryl Ester Transfer Protein Gene and Risk for Coronary Heart Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Circulation Research Vol. 121, No. 1 ( 2017-06-23), p. 81-88
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 121, No. 1 ( 2017-06-23), p. 81-88
    Abstract: Therapies that inhibit CETP (cholesteryl ester transfer protein) have failed to demonstrate a reduction in risk for coronary heart disease (CHD). Human DNA sequence variants that truncate the CETP gene may provide insight into the efficacy of CETP inhibition. Objective: To test whether protein-truncating variants (PTVs) at the CETP gene were associated with plasma lipid levels and CHD. Methods and Results: We sequenced the exons of the CETP gene in 58 469 participants from 12 case–control studies (18 817 CHD cases, 39 652 CHD-free controls). We defined PTV as those that lead to a premature stop, disrupt canonical splice sites, or lead to insertions/deletions that shift frame. We also genotyped 1 Japanese-specific PTV in 27561 participants from 3 case–control studies (14 286 CHD cases, 13 275 CHD-free controls). We tested association of CETP PTV carrier status with both plasma lipids and CHD. Among 58 469 participants with CETP gene-sequencing data available, average age was 51.5 years and 43% were women; 1 in 975 participants carried a PTV at the CETP gene. Compared with noncarriers, carriers of PTV at CETP had higher high-density lipoprotein cholesterol (effect size, 22.6 mg/dL; 95% confidence interval, 18–27; P 〈 1.0×10 −4 ), lower low-density lipoprotein cholesterol (−12.2 mg/dL; 95% confidence interval, −23 to −0.98; P =0.033), and lower triglycerides (−6.3%; 95% confidence interval, −12 to −0.22; P =0.043). CETP PTV carrier status was associated with reduced risk for CHD (summary odds ratio, 0.70; 95% confidence interval, 0.54–0.90; P =5.1×10 −3 ). Conclusions: Compared with noncarriers, carriers of PTV at CETP displayed higher high-density lipoprotein cholesterol, lower low-density lipoprotein cholesterol, lower triglycerides, and lower risk for CHD.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/CIRCRESAHA.117.311145
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 1467838-X
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  • 6
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    AKI and Long-Term Risk for Cardiovascular Events and Mortality
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Journal of the American Society of Nephrology Vol. 28, No. 1 ( 2017-1), p. 377-387
    Details
    In: Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 28, No. 1 ( 2017-1), p. 377-387
    Abstract: AKI associates with increased long-term risk of mortality, but the prognostic significance of AKI in terms of long-term cardiovascular disease remains unconfirmed. We conducted a systematic review and meta-analysis to assess whether AKI associates with long-term cardiovascular disease. We included cohort studies that examined adults with and without AKI and reported a multivariable-adjusted relative risk (RR) for the association between AKI and cardiovascular mortality, major cardiovascular events, and disease-specific events: congestive heart failure, acute myocardial infarction, and stroke. Twenty-five studies involving 254,408 adults (55,150 with AKI) were included. AKI associated with an 86% and a 38% increased risk of cardiovascular mortality and major cardiovascular events, respectively ([RR 1.86; 95% confidence interval (95% CI), 1.72 to 2.01] and [RR 1.38; 95% CI, 1.23 to 1.55] , respectively). For disease-specific events, AKI associated with a 58% increased risk of heart failure (RR 1.58; 95% CI, 1.46 to 1.72) and a 40% increased risk of acute myocardial infarction (RR 1.40; 95% CI, 1.23 to 1.59). The elevated risk of heart failure and acute myocardial infarction persisted in subgroup analyses on the basis of AKI severity and the proportion of adults with baseline ischemic heart disease. Finally, AKI was associated with a 15% increased risk of stroke (RR 1.15; 95% CI, 1.03 to 1.28). In conclusion, AKI associates with an elevated risk of cardiovascular mortality and major cardiovascular events, particularly heart failure and acute myocardial infarction.
    Type of Medium: Online Resource
    ISSN: 1046-6673 , 1533-3450
    URL: Article
    DOI: 10.1681/ASN.2016010105
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2029124-3
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  • 7
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    Genetic Analysis of Venous Thromboembolism in UK Biobank Identifies the ZFPM2 Locus and Implicates Obesity as a Causal Risk Factor
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Circulation: Cardiovascular Genetics Vol. 10, No. 2 ( 2017-04)
    Details
    In: Circulation: Cardiovascular Genetics, Ovid Technologies (Wolters Kluwer Health), Vol. 10, No. 2 ( 2017-04)
    Abstract: UK Biobank is the world’s largest repository for phenotypic and genotypic information for individuals of European ancestry. Here, we leverage UK Biobank to understand the inherited basis for venous thromboembolism (VTE), a leading cause of cardiovascular mortality. Methods and Results— We identified 3290 VTE cases and 116 868 controls through billing code–based phenotyping. We performed a genome-wide association study for VTE with ≈9 000 000 imputed single-nucleotide polymorphisms. We performed a phenome-wide association study for a genetic risk score of 10 VTE-associated variants. To assess whether obesity is a causal factor for VTE, we performed Mendelian randomization analysis using a genetic risk score instrument composed of 68 body mass index–associated variants. The genome-wide association study for VTE replicated previous findings at the F5 , F2 , ABO , F11 , and FGG loci. We identified 1 new locus— ZFPM2 rs4602861—at genome-wide significance (odds ratio, 1.11; 95% confidence interval, 1.07–1.15; P =4.9×10 −10 ) and a new independent variant at the F2 locus (rs3136516; odds ratio, 1.10; 95% confidence interval, 1.06–1.13; P =7.60×10 −9 ). In a phenome-wide association study, a 10 single-nucleotide polymorphism VTE genetic risk score was associated with coronary artery disease (odds ratio, 1.08; 95% confidence interval, 1.05–1.10 per unit increase in VTE odds; P =1.08×10 −9 ). In a Mendelian randomization analysis, genetically elevated body mass index (a 1 SD increase) was associated with 57% higher risk of VTE (odds ratio, 1.57; 95% confidence interval, 1.08–1.97; P =0.003). Conclusions— For common diseases such as VTE, biobanks provide potential to perform genetic discovery, explore the phenotypic consequences for disease-associated variants, and test causal inference.
    Type of Medium: Online Resource
    ISSN: 1942-325X , 1942-3268
    URL: Article
    DOI: 10.1161/CIRCGENETICS.116.001643
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2927603-2
    detail.hit.zdb_id: 2457085-0
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  • 8
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    Abstract 12563: Variation in Referral for Specialist Follow-Up and 30-Day Mortality in Patients Hospitalized With Heart Failure in England and Wales
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Circulation Vol. 130, No. suppl_2 ( 2014-11-25)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 130, No. suppl_2 ( 2014-11-25)
    Abstract: Introduction: Current US and European guidelines recommend that patients hospitalized with heart failure (HF) are followed up after discharge, but do not specify whether or not this should be with HF specialist services. We investigated referral patterns to specialist services amongst hospitals in England and Wales and assessed whether these differences were associated with 30-day mortality. Methods: We used data from the National Heart Failure Audit, which included 84647 HF patients from 176 hospitals. Vital status was obtained from the UK national death registry. Using hierarchical statistical models and instrumental variable analysis, we estimated whether different types of follow-up (cardiologist, HF nurse or geriatrician) were associated with 30-day mortality, adjusting for case mix. Results: At the hospital level, rates of referral to cardiologists for follow up varied from 4% to 94%, to HF nurses from 0% to 97% and to geriatricians from 0% to 65%. When heart failure patients were referred for follow-up to a heart failure nurse, to a geriatrician, or to a cardiologist, they were 15%, 15% and 47% less likely to die than patients who were not referred to these specialists (odds ratio [OR] = 0.85, p 〈 0.001; OR = 0.85, p 〈 0.001; OR = 0.53, p 〈 0.001). A patient admitted to one randomly selected UK hospital would have, on average, 2.1-fold odds of receiving referral to a cardiologist for follow up than a second similar patient admitted to another randomly selected hospital (95% confidence interval [CI]: 1.9, 2.3) Use of quintile of hospital preference as an instrumental variable for cardiology referral resulted in a consistent estimate for the effect of cardiology referral on 30-day mortality (OR=0.65, CI: 0.40, 0.90, p=0.005). Conclusion: Referral at discharge to cardiology services for follow-up varies considerably amongst UK hospitals. At both an individual patient and at a hospital level, referral to cardiology for follow-up is a major determinant of 30-day mortality.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.130.suppl_2.12563
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 1466401-X
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  • 9
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    Phenotypic Consequences of a Genetic Predisposition to Enhanced Nitric Oxide Signaling
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Circulation Vol. 137, No. 3 ( 2018-01-16), p. 222-232
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 137, No. 3 ( 2018-01-16), p. 222-232
    Abstract: Nitric oxide signaling plays a key role in the regulation of vascular tone and platelet activation. Here, we seek to understand the impact of a genetic predisposition to enhanced nitric oxide signaling on risk for cardiovascular diseases, thus informing the potential utility of pharmacological stimulation of the nitric oxide pathway as a therapeutic strategy. Methods: We analyzed the association of common and rare genetic variants in 2 genes that mediate nitric oxide signaling (Nitric Oxide Synthase 3 [ NOS3 ] and Guanylate Cyclase 1, Soluble, Alpha 3 [ GUCY1A3 ]) with a range of human phenotypes. We selected 2 common variants (rs3918226 in NOS3 and rs7692387 in GUCY1A3 ) known to associate with increased NOS3 and GUCY1A3 expression and reduced mean arterial pressure, combined them into a genetic score, and standardized this exposure to a 5 mm Hg reduction in mean arterial pressure. Using individual-level data from 335 464 participants in the UK Biobank and summary association results from 7 large-scale genome-wide association studies, we examined the effect of this nitric oxide signaling score on cardiometabolic and other diseases. We also examined whether rare loss-of-function mutations in NOS3 and GUCY1A3 were associated with coronary heart disease using gene sequencing data from the Myocardial Infarction Genetics Consortium (n=27 815). Results: A genetic predisposition to enhanced nitric oxide signaling was associated with reduced risks of coronary heart disease (odds ratio, 0.37; 95% confidence interval [CI], 0.31-0.45; P =5.5*10 –26 ], peripheral arterial disease (odds ratio 0.42; 95% CI, 0.26-0.68; P =0.0005), and stroke (odds ratio, 0.53; 95% CI, 0.37-0.76; P =0.0006). In a mediation analysis, the effect of the genetic score on decreased coronary heart disease risk extended beyond its effect on blood pressure. Conversely, rare variants that inactivate the NOS3 or GUCY1A3 genes were associated with a 23 mm Hg higher systolic blood pressure (95% CI, 12-34; P =5.6*10 –5 ) and a 3-fold higher risk of coronary heart disease (odds ratio, 3.03; 95% CI, 1.29-7.12; P =0.01). Conclusions: A genetic predisposition to enhanced nitric oxide signaling is associated with reduced risks of coronary heart disease, peripheral arterial disease, and stroke. Pharmacological stimulation of nitric oxide signaling may prove useful in the prevention or treatment of cardiovascular disease.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.117.028021
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 1466401-X
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  • 10
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    Gene Sequencing Identifies Perturbation in Nitric Oxide Signaling as a Nonlipid Molecular Subtype of Coronary Artery Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Circulation: Genomic and Precision Medicine Vol. 15, No. 6 ( 2022-12)
    Details
    In: Circulation: Genomic and Precision Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 15, No. 6 ( 2022-12)
    Abstract: A key goal of precision medicine is to disaggregate common, complex diseases into discrete molecular subtypes. Rare coding variants in the low-density lipoprotein receptor gene ( LDLR ) are identified in 1% to 2% of coronary artery disease (CAD) patients, defining a molecular subtype with risk driven by hypercholesterolemia. Methods: To search for additional subtypes, we compared the frequency of rare, predicted loss-of-function and damaging missense variants aggregated within a given gene in 41 081 CAD cases versus 217 115 controls. Results: Rare variants in LDLR were most strongly associated with CAD, present in 1% of cases and associated with 4.4-fold increased CAD risk. A second subtype was characterized by variants in endothelial nitric oxide synthase gene ( NOS3 ), a key enzyme regulating vascular tone, endothelial function, and platelet aggregation. A rare predicted loss-of-function or damaging missense variants in NOS3 was present in 0.6% of cases and associated with 2.42-fold increased risk of CAD (95% CI, 1.80–3.26; P =5.50×10 −9 ). These variants were associated with higher systolic blood pressure (+3.25 mm Hg; [95% CI, 1.86–4.65]; P =5.00×10 −6 ) and increased risk of hypertension (adjusted odds ratio 1.31; [95% CI, 1.14–1.51]; P =2.00×10 −4 ) but not circulating cholesterol concentrations, suggesting that, beyond lipid pathways, nitric oxide synthesis is a key nonlipid driver of CAD risk. Conclusions: Beyond LDLR , we identified an additional nonlipid molecular subtype of CAD characterized by rare variants in the NOS3 gene.
    Type of Medium: Online Resource
    ISSN: 2574-8300
    URL: Article
    DOI: 10.1161/CIRCGEN.121.003598
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2927603-2
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