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1.
Artigo em Espanhol | MEDLINE | ID: mdl-33069629

RESUMO

We present the adaptation for Spain of the updated European Cardiovascular Prevention Guidelines. In this update, greater stress is laid on the population approach, and especially on the promotion of physical activity and healthy diet through dietary, leisure and active transport policies in Spain. To estimate vascular risk, note should be made of the importance of recalibrating the tables used, by adapting them to population shifts in the prevalence of risk factors and incidence of vascular diseases, with particular attention to the role of chronic kidney disease. At an individual level, the key element is personalised support for changes in behaviour, adherence to medication in high-risk individuals and patients with vascular disease, the fostering of physical activity, and cessation of smoking habit. Furthermore, recent clinical trials with PCSK9 inhibitors are reviewed, along with the need to simplify pharmacological treatment of arterial hypertension to improve control and adherence to treatment. In the case of patients with type 2 diabetes mellitus and vascular disease or high vascular disease risk, when lifestyle changes and metformin are inadequate, the use of drugs with proven vascular benefit should be prioritised. Lastly, guidelines on peripheral arterial disease and other specific diseases are included, as is a recommendation against prescribing antiaggregants in primary prevention.

2.
J Am Heart Assoc ; 9(20): e017159, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33054490

RESUMO

Background Coronary artery disease remains a major cause of death despite better outcomes of ST-segment-elevation myocardial infarction (STEMI). We aimed to analyze data from the Ruti-STEMI registry of in-hospital, 28-day, and 1-year events in patients with STEMI over the past 3 decades in Catalonia, Spain, to assess trends in STEMI prognosis. Methods and Results Between February 1989 and December 2017, a total of 7589 patients with STEMI were admitted consecutively. Patients were grouped into 5 periods: 1989 to 1994 (period 1), 1995 to 1999 (period 2), 2000 to 2004 (period 3), 2005 to 2009 (period 4), and 2010 to 2017 (period 5). We used Cox regression to compare 28-day and 1-year STEMI mortality and in-hospital complication trends across these periods. Mean patient age was 61.6±12.6 years, and 79.3% were men. The 28-day all-cause mortality declined from period 1 to period 5 (10.4% versus 6.0%; P<0.001), with a 40% reduction after multivariable adjustment (hazard ratio [HR], 0.6; 95% CI, 0.46-0.80; P<0.001). One-year all-cause mortality declined from period 1 to period 5 (11.7% versus 9.0%; P=0.001), with a 24% reduction after multivariable adjustment (HR, 0.76; 95% CI, 0.60-0.98; P=0.036). A significant temporal reduction was observed for in-hospital complications including postinfarct angina (-78%), ventricular tachycardia (-57%), right ventricular dysfunction (-48%), atrioventricular block (-45%), pericarditis (-63%), and free wall rupture (-53%). Primary ventricular fibrillation showed no significant downslope trend. Conclusions In-hospital STEMI complications and 28-day and 1-year mortality rates have dropped markedly in the past 30 years. Reducing ischemia-driven primary ventricular fibrillation remains a major challenge.

3.
Rev Esp Salud Publica ; 942020 Sep 11.
Artigo em Espanhol | MEDLINE | ID: mdl-32915170

RESUMO

We present the adaptation for Spain of the updated European Cardiovascular Prevention Guidelines. In this update, greater stress is laid on the population approach, and especially on the promotion of physical activity and healthy diet through dietary, leisure and active transport policies in Spain. To estimate vascular risk, note should be made of the importance of recalibrating the tables used, by adapting them to population shifts in the prevalence of risk factors and incidence of vascular diseases, with particular attention to the role of chronic kidney disease. At an individual level, the key element is personalised support for changes in behaviour, adherence to medication in high-risk individuals and patients with vascular disease, the fostering of physical activity, and cessation of smoking habit. Furthermore, recent clinical trials with PCSK9 inhibitors are reviewed, along with the need to simplify pharmacological treatment of arterial hypertension to improve control and adherence to treatment. In the case of patients with type 2 diabetes mellitus and vascular disease or high vascular disease risk, when lifestyle changes and metformin are inadequate, the use of drugs with proven vascular benefit should be prioritised. Lastly, guidelines on peripheral arterial disease and other specific diseases are included, as is a recommendation against prescribing antiaggregants in primary prevention.

4.
Rev. esp. cardiol. (Ed. impr.) ; 73(9): 758-762, sept. 2020. ilus, tab, graf
Artigo em Espanhol | IBECS-Express | IBECS | ID: ibc-ET1-6276

RESUMO

El síndrome de Bayés es una nueva entidad clínica, caracterizada por la combinación de bloqueo interauricular (BIA) avanzado en el electrocardiograma de superficie con fibrilación auricular (FA) y otras arritmias auriculares. Este síndrome se asocia con un riesgo incrementado de ictus, demencia y mortalidad. El BIA avanzado se diagnostica con la presencia de una onda P ≥ 120ms de morfología bifásica (±) en derivaciones de cara inferior. Se produce por un bloqueo completo del haz de Bachmann que causa una despolarización retrógrada de la aurícula izquierda desde zonas cercanas a la unión auriculoventricular. La miocardiopatía auricular fibrótica es el sustrato anatómico del BIA avanzado. La disincronía inducida por el BIA avanzado funciona como desencadenante y mecanismo de mantenimiento de la FA. Esta alteración de la arquitectura auricular produce remodelado auricular, estasis sanguínea e hipercoagulabilidad, lo cual desencadena la cascada trombogénica. El BIA avanzado, incluso sin arritmias auriculares documentadas, también se ha relacionado con FA, ictus, demencia y mortalidad. Sin embargo, todavía no se ha demostrado el beneficio de la anticoagulación para los pacientes sin FA documentada. Por lo tanto, es recomendable una búsqueda proactiva de FA en los pacientes con BIA avanzado


Bayés syndrome is a new clinical entity, characterized by the association of advanced interatrial block (IAB) on surface electrocardiogram with atrial fibrillation (AF) and other atrial arrhythmias. This syndrome is associated with an increased risk of stroke, dementia, and mortality. Advanced IAB is diagnosed by the presence of a P-wave ≥ 120ms with biphasic morphology (±) in inferior leads. The cause of IAB is complete Bachmann bundle blockade, leading to retrograde depolarization of the left atrium from areas near the atrioventricular junction. The anatomic substrate of advanced IAB is fibrotic atrial cardiomyopathy. Dyssynchrony induced by advanced IAB is a trigger and maintenance mechanism of AF. This alteration of the atrial architecture produces atrial remodeling, blood stasis and hypercoagulability, triggering the thrombogenic cascade. The presence of advanced IAB, even in patients without documented atrial arrhythmias, has also been associated with AF, stroke, dementia, and mortality. However, in these patients, there is no evidence to support the use of anticoagulation. Therefore, in patients with advanced IAB, a proactive search for AF is recommended

5.
Metabolism ; 112: 154351, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32891675

RESUMO

BACKGROUND: To assess whether genetically determined quantitative and qualitative HDL characteristics were independently associated with coronary artery disease (CAD). METHODS: We designed a two-sample multivariate Mendelian randomization study with available genome-wide association summary data. We identified genetic variants associated with HDL cholesterol and apolipoprotein A-I levels, HDL size, particle levels, and lipid content to define our genetic instrumental variables in one sample (Kettunen et al. study, n = 24,925) and analyzed their association with CAD risk in a different study (CARDIoGRAMplusC4D, n = 184,305). We validated these results by defining our genetic variables in another database (METSIM, n = 8372) and studied their relationship with CAD in the CARDIoGRAMplusC4D dataset. To estimate the effect size of the associations of interest adjusted for other lipoprotein traits and minimize potential pleiotropy, we used the Multi-trait-based Conditional & Joint analysis. RESULTS: Genetically determined HDL cholesterol and apolipoprotein A-I levels were not associated with CAD. HDL mean diameter (ß = 0.27 [95%CI = 0.19; 0.35]), cholesterol levels in very large HDLs (ß = 0.29 [95%CI = 0.17; 0.40]), and triglyceride content in very large HDLs (ß = 0.14 [95%CI = 0.040; 0.25]) were directly associated with CAD risk, whereas the cholesterol content in medium-sized HDLs (ß = -0.076 [95%CI = -0.10; -0.052]) was inversely related to this risk. These results were validated in the METSIM-CARDIoGRAMplusC4D data. CONCLUSIONS: Some qualitative HDL characteristics (related to size, particle distribution, and cholesterol and triglyceride content) are related to CAD risk while HDL cholesterol levels are not.

6.
Circ Genom Precis Med ; 13(5): 417-423, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32862661

RESUMO

BACKGROUND: Familial sitosterolemia is a rare Mendelian disorder characterized by hyperabsorption and decreased biliary excretion of dietary sterols. Affected individuals typically have complete genetic deficiency-homozygous loss-of-function (LoF) variants-in the ABCG5 or ABCG8 genes and have substantially elevated plasma sitosterol and LDL (low-density lipoprotein) cholesterol (LDL-C) levels. The impact of partial genetic deficiency of ABCG5 or ABCG8-as occurs in heterozygous carriers of LoF variants-on LDL-C and risk of coronary artery disease (CAD) has remained uncertain. METHODS: We first recruited 9 sitosterolemia families, identified causative LoF variants in ABCG5 or ABCG8, and evaluated the associations of these ABCG5 or ABCG8 LoF variants with plasma phytosterols and lipid levels. We next assessed for LoF variants in ABCG5 or ABCG8 in CAD cases (n=29 321) versus controls (n=357 326). We tested the association of rare LoF variants in ABCG5 or ABCG8 with blood lipids and risk for CAD. Rare LoF variants were defined as protein-truncating variants with minor allele frequency <0.1% in ABCG5 or ABCG8. RESULTS: In sitosterolemia families, 7 pedigrees harbored causative LoF variants in ABCG5 and 2 pedigrees in ABCG8. Homozygous LoF variants in either ABCG5 or ABCG8 led to marked elevations in sitosterol and LDL-C. Of those sitosterolemia families, heterozygous carriers of ABCG5 LoF variants exhibited increased sitosterol and LDL-C levels compared with noncarriers. Within large-scale CAD case-control cohorts, prevalence of rare LoF variants in ABCG5 and in ABCG8 was ≈0.1% each. ABCG5 heterozygous LoF variant carriers had significantly elevated LDL-C levels (25 mg/dL [95% CI, 14-35]; P=1.1×10-6) and were at 2-fold increased risk of CAD (odds ratio, 2.06 [95% CI, 1.27-3.35]; P=0.004). By contrast, ABCG8 heterozygous LoF carrier status was not associated with increased LDL-C or risk of CAD. CONCLUSIONS: Although familial sitosterolemia is traditionally considered as a recessive disorder, we observed that heterozygous carriers of an LoF variant in ABCG5 had significantly increased sitosterol and LDL-C levels and a 2-fold increase in risk of CAD.

7.
Am J Cardiol ; 136: 94-99, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32946858

RESUMO

The association between atrial fibrillation, stroke, and interatrial block (IAB) (P-wave duration ≥120 ms) is well recognized, particularly in the case of advanced IAB. We aimed to assess the association of IAB with mild cognitive impairment. Advanced Characterization of Cognitive Impairment in Elderly with Interatrial Block was a case-control multicenter study, conducted in subjects aged ≥70 years in sinus rhythm without significant structural heart disease. Diagnosis of mild cognitive impairment was performed by an expert geriatrician, internist, or neurologist in the presence of changes in cognitive function (Mini Mental State Examination score 20 to 25) without established dementia. A total of 265 subjects were included. Mean age was 79.6 ± 6.3 years and 174 (65.7%) were women; there were 143 cases with mild cognitive impairment and 122 controls with normal cognitive function. Compared with controls, cases had longer P-wave duration (116.2 ± 13.8 ms vs 112.5 ± 13.3 ms, p = 0.028), higher prevalence of IAB (73 [51.0%] vs 38 [31.1%], p = 0.001), higher prevalence of advanced IAB (28 [19.6%] vs 10 [8.2%], p = 0.002), and higher MVP ECG risk score (2.7 ± 1.4 vs 2.2 ± 1.3, p = 0.004). IAB was independently associated with mild cognitive impairment, both for partial (odds ratio 2.0, 95% CI: 1.1 to 3.9) and advanced IAB (odds ratio 2.8, 95% CI: 1.1 to 6.7). In conclusion, in subjects aged ≥70 years without significant structural heart disease, IAB is independently associated with mild cognitive impairment. This association is stronger in the case of advanced IAB.

8.
Am J Clin Nutr ; 112(5): 1200-1211, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-32930325

RESUMO

BACKGROUND: Epigenome-wide association studies identified the cg00574958 DNA methylation site at the carnitine palmitoyltransferase-1A (CPT1A) gene to be associated with reduced risk of metabolic diseases (hypertriglyceridemia, obesity, type 2 diabetes, hypertension, metabolic syndrome), but the mechanism underlying these associations is unknown. OBJECTIVES: We aimed to elucidate whether carbohydrate and fat intakes modulate cg00574958 methylation and the risk of metabolic diseases. METHODS: We examined associations between carbohydrate (CHO) and fat (FAT) intake, as percentages of total diet energy, and the CHO/FAT ratio with CPT1A-cg00574958, and the risk of metabolic diseases in 3 populations (Genetics of Lipid Lowering Drugs and Diet Network, n = 978; Framingham Heart Study, n = 2331; and REgistre GIroní del COR study, n = 645) while adjusting for confounding factors. To understand possible causal effects of dietary intake on the risk of metabolic diseases, we performed meta-analysis, CPT1A transcription analysis, and mediation analysis with CHO and FAT intakes as exposures and cg00574958 methylation as the mediator. RESULTS: We confirmed strong associations of cg00574958 methylation with metabolic phenotypes (BMI, triglyceride, glucose) and diseases in all 3 populations. Our results showed that CHO intake and CHO/FAT ratio were positively associated with cg00574958 methylation, whereas FAT intake was negatively correlated with cg00574958 methylation. Meta-analysis further confirmed this strong correlation, with ß = 58.4 ± 7.27, P = 8.98 x 10-16 for CHO intake; ß = -36.4 ± 5.95, P = 9.96 x 10-10 for FAT intake; and ß = 3.30 ± 0.49, P = 1.48 x 10-11 for the CHO/FAT ratio. Furthermore, CPT1A mRNA expression was negatively associated with CHO intake, and positively associated with FAT intake, and metabolic phenotypes. Mediation analysis supports the hypothesis that CHO intake induces CPT1A methylation, hence reducing the risk of metabolic diseases, whereas FAT intake inhibits CPT1A methylation, thereby increasing the risk of metabolic diseases. CONCLUSIONS: Our results suggest that the proportion of total energy supplied by CHO and FAT can have a causal effect on the risk of metabolic diseases via the epigenetic status of CPT1A.Study registration at https://www.clinicaltrials.gov/: the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN)-NCT01023750; and the Framingham Heart Study (FHS)-NCT00005121.

9.
Open Heart ; 7(2)2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32747454

RESUMO

OBJECTIVE: Primary percutaneous coronary intervention (P-PCI) has demonstrated its efficacy in patients with ST segment elevation myocardial infarction (STEMI). However, patients with STEMI ≥75 years receive less P-PCI than younger patients despite their higher in-hospital morbimortality. The objective of this analysis was to determine the effectiveness of P-PCI in patients with STEMI ≥75 years. METHODS: We included 979 patients with STEMI ≥75 years, from the ATención HOspitalaria del Síndrome coronario study, a registry of 8142 consecutive patients with acute coronary syndrome admitted at 31 Spanish hospitals in 2014-2016. We calculated a propensity score (PS) for the indication of P-PCI. Patients that received or not P-PCI were matched by PS. Using logistic regression, we compared the effectiveness of performing P-PCI versus non-performance for the composite primary event, which included death, reinfarction, acute pulmonary oedema or cardiogenic shock during hospitalisation. RESULTS: Of the included patients, 81.5 % received P-PCI. The matching provided two groups of 169 patients with and without P-PCI. Compared with its non-performance, P-PCI presented a composite event OR adjusted by PS of 0.55 (95% CI 0.34 to 0.89). CONCLUSIONS: Receiving a P-PCI was significantly associated with a reduced risk of major intrahospital complications in patients with STEMI aged 75 years or older.

10.
Int J Cardiol ; 321: 95-98, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32810550

RESUMO

BACKGROUND: An association between interatrial block (IAB) (P wave duration ≥120 ms) and dementia has been suggested. Our objective was to assess the association of IAB with cognitive impairment (CI). METHODS: The prospective BAYES registry included 552 patients ≥70 years with structural heart disease without documented atrial fibrillation. Cognitive ability was assessed at baseline and every 6 months with the Pfeiffer test. The median follow-up was 22 months. RESULTS: Thirty patients (5.4%) had baseline CI, 20 patients with mild CI and 10 with moderate CI. Compared to patients without CI, patients with CI had higher mean age (80.4 ±â€¯6.5 vs. 76.8 ±â€¯5.4 years) and higher prevalence of advanced IAB (with biphasic P-wave ± in inferior leads) (14 [46.7%] vs. 122 [23.4%], p < .01). The prevalence of baseline CI was 2.7% in normal P-wave, 5.1% in partial IAB, and 10.3% in advanced IAB, p < .001. Advanced IAB was independently associated with baseline CI (odds ratio 4.9, 95% confidence interval 1.4-16.5), this was not the case with partial IAB (odds ratio 2.1, 95% confidence interval 0.5-7.4). The independent association with CI at follow-up existed both for partial IAB (hazard ratio 1.98, 95% confidence interval 1.18-3.33) and advanced IAB (hazard ratio 2.04, 95% confidence interval 1.19-3.51). CONCLUSION: In patients aged 70 years or more with structural heart disease who are in sinus rhythm advanced IAB is associated with baseline CI. There is also an association of partial and advanced IAB with CI during follow-up.

11.
Eur Heart J Acute Cardiovasc Care ; : 2048872620936038, 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32672051

RESUMO

BACKGROUND: Coronary care units were established in the 1960s to reduce acute-phase mortality in acute coronary syndrome. In the 21st century, the original coronary care unit concept has evolved into an intensive cardiovascular care unit. The aim of this study was to analyse trend changes in characteristics and mortality of patients admitted to a coronary care unit over the past three decades. METHOD: Between February 1989 and December 2017, a total of 18,334 patients was consecutively admitted to the coronary care unit of a university hospital in Barcelona. Data were analysed in five time frames: 1989-1994, 1995-1999, 2000-2004, 2005-2009 and 2010-2017. We analysed demographic profile, diagnoses at admission and trend changes in mortality across periods. RESULTS: During the periods, the patients' ages and comorbidities increased. Diagnoses at admission have evolved. Acute coronary syndrome cases declined from the first to the last period (72.6% vs. 62.8%) while heart failure (6.0% vs. 8.6%) and malignant arrhythmias (0.8% vs. 4.0%) increased significantly. Overall, coronary care unit mortality decreased 34% from the first to the last period (6.8% vs. 4.5%, P<0.001). Furthermore, the cause of death has changed, those due to acute coronary syndrome declining (66.7% vs. 45.5%), and death from malignant arrhythmias increasing (1.9% vs. 16.2%) from the first to the last period. CONCLUSIONS: Although acute coronary syndrome remained the main diagnosis, heart failure and arrhythmias have increased. Despite the aging and comorbidities, overall mortality in the coronary care unit decreased by 34% in the past three decades. Deaths due to acute coronary syndrome have declined, whereas those due to malignant arrhythmias have increased.

12.
Rev Esp Cardiol (Engl Ed) ; 73(9): 758-762, 2020 Sep.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32684442

RESUMO

Bayés syndrome is a new clinical entity, characterized by the association of advanced interatrial block (IAB) on surface electrocardiogram with atrial fibrillation (AF) and other atrial arrhythmias. This syndrome is associated with an increased risk of stroke, dementia, and mortality. Advanced IAB is diagnosed by the presence of a P-wave ≥ 120ms with biphasic morphology (±) in inferior leads. The cause of IAB is complete Bachmann bundle blockade, leading to retrograde depolarization of the left atrium from areas near the atrioventricular junction. The anatomic substrate of advanced IAB is fibrotic atrial cardiomyopathy. Dyssynchrony induced by advanced IAB is a trigger and maintenance mechanism of AF. This alteration of the atrial architecture produces atrial remodeling, blood stasis and hypercoagulability, triggering the thrombogenic cascade. The presence of advanced IAB, even in patients without documented atrial arrhythmias, has also been associated with AF, stroke, dementia, and mortality. However, in these patients, there is no evidence to support the use of anticoagulation. Therefore, in patients with advanced IAB, a proactive search for AF is recommended.

13.
Clin Appl Thromb Hemost ; 26: 1076029620915286, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584610

RESUMO

The aim of this study was to determine whether genetic variants in FADS1/FADS2 and ELOVL2 are associated with overweight-obesity and body mass index (BMI) and to assess the association between these genetic variants and lipid profile and fatty acid levels. A total of 259 overweight-obese patients were compared to 369 healthy controls. FADS1, FADS2, and ELOVL2 genes were associated with BMI and overweight-obesity (P ≤ .001). In an additive model, the C allele in each of these variants was associated with a lower BMI: -1.18, -0.90, and -1.23 units, respectively. Higher amounts of total cholesterol, low-density lipoprotein cholesterol, total saturated fatty acids (lauric [12:0], myristic [C14:0], palmitic [C16:0], stearic [C18:0], arachidic [20:0], lignoceric [24:0]), monounsaturated fatty acids (myristoleic [C14:1], erucic [C22:1 n-9]), and polyunsaturated fatty acids (α-linolenic [ALA, 18:3 n-3], docosahexaenoic [DHA, C22:6 n-3], eicosapentaenoic acid [EPA, C20:5n-3], arachidonic acid [AA, 20:4n-6], and conjugated linolenic acids [CLA1 and CLA2]) were shown in patients. A significant increase in D6D activities presented by 20:4n-6/18:2n-6 and 18:3n-6/18:2n-6, Δ9 desaturase (D9D) activity, estimated by the ratio 18:1n-9/18:0 and elongase activities (AE), and estimated by the ratio of docosatetraenoic/AA and DPA/EPA in patients. The C minor allele of FADS1 had significantly lower DHA. A significant decrease in stearic acid, EPA, and AE activity (docosatetraenoic/AA) was revealed in patients with the minor allele carriers of FADS2. The C minor allele of ELOVL2 had significantly lower ALA, EPA, DPA, and D6D activity (C20:4 n-6/C18:2n-6). These data suggest that variations in FADS1, FADS2, and ELOVL2 affect the risk of overweight-obesity and the level of circulating fatty acids and could point to a key molecular pathway of metabolic syndrome and its related comorbidities.

14.
J Renin Angiotensin Aldosterone Syst ; 21(2): 1470320320907820, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32356512

RESUMO

OBJECTIVE: This study aims to determine whether genetic variants in ACE I/D and AGT M235T are associated with overweight-obesity and body mass index (BMI) in a Tunisian population. METHODS: We designed an age- and sex-matched case-control study. The height and weight were measured and BMI was calculated. A total of 259 overweight-obese patients and 369 healthy controls were genotyped for the ACE I/D and AGT M235T genes using polymerase chain reaction and restriction fragment length polymorphism. RESULTS: ACE I/D and AGT M235T genes were associated with BMI, waist circumference and overweight-obesity (p⩽0.001). In an additive model, the I and the M alleles in ACE and AGT variants, respectively, were associated with a lower BMI: -1.45 and -2.29 units, respectively. ACE I/D genotypes were associated with dyslipidemia; AGT M235T genotypes with dyslipidemia and total cholesterol. CONCLUSION: These data suggest that variations in ACE I/D and AGT M235T affect the risk of overweight-obesity, BMI and dyslipidemia, and could point to a key molecular pathway of metabolic syndrome and its related comorbidities.

15.
Europace ; 22(7): 1001-1008, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32449904

RESUMO

AIMS: Advanced interatrial block (IAB), is an unrecognized surrogate of atrial dysfunction and a trigger of atrial dysrhythmias, mainly atrial fibrillation (AF). Our aim was to prospectively assess whether advanced IAB in sinus rhythm is associated with AF and stroke in elderly outpatients with structural heart disease, a group not previously studied. METHODS AND RESULTS: Prospective observational registry that included outpatients aged ≥70 years with structural heart disease and no previous diagnosis of AF. Patients were divided into three groups: normal P-wave duration (<120 ms), partial IAB (P-wave duration ≥120 ms, positive in the inferior leads), and advanced IAB [P-wave duration ≥120 ms, biphasic (plus/minus) morphology in the inferior leads]. Among 556 individuals, 223 had normal P-wave (40.1%), 196 partial IAB (35.3%), and 137 advanced IAB (24.6%). After a median follow-up of 694 days, 93 patients (16.7%) developed AF, 30 stroke (5.4%), and 34 died (6.1%). Advanced IAB was independently associated with AF -[hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.7-5.1; P < 0.001], stroke [HR 3.8, 95% CI 1.4-10.7; P = 0.010), and AF/stroke (HR 2.6, 95% CI 1.5-4.4; P = 0.001). P-wave duration (ms) was independently associated with AF (HR 1.05, 95% CI 1.03-1.07; P < 0.001), AF/stroke (HR 1.04, 95% CI 1.02-1.06; P < 0.001), and mortality (HR 1.04, 95% CI 1.00-1.08; P = 0.021). CONCLUSIONS: The presence of advanced IAB in sinus rhythm is independently associated with AF and stroke in an elderly population with structural heart disease and no previous diagnosis of AF. P-wave duration was also associated with all-cause mortality.

16.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32446794

RESUMO

INTRODUCTION AND OBJECTIVES: Regular leisure-time physical activity (LTPA) has been consistently recognized as a protective factor for cardiovascular diseases (CVD) and all-cause mortality. However, the pattern of this relationship is still not clear. The aim of this study was to assess the relationship of LTPA with incident CVD and mortality in a Spanish population. METHODS: A prospective population-based cohort of 11 158 randomly selected inhabitants from the general population. LTPA was assessed by a validated questionnaire. Mortality and CVD outcomes were registered during the follow-up (median: 7.24 years). The association between LTPA and outcomes of interest (all-cause mortality and cardiovascular disease) was explored using a generalized additive model with penalized smoothing splines and multivariate Cox proportional hazard models. RESULTS: We observed a significant nonlinear association between LTPA and all-cause and CVD mortality, and fatal and nonfatal CVD. Moderate-vigorous intensity LTPA, but not light-intensity LTPA, were associated with beneficial effects. The smoothing splines identified a cutoff at 400 MET-min/d. Below this threshold, each increase of 100 MET-min/d in moderate-vigorous LTPA contributed with a 16% risk reduction in all-cause mortality (HR, 0.84; 95%CI, 0.77-0.91), a 27% risk reduction in CVD mortality (HR, 0.73; 95%CI, 0.61-0.87), and a 12% risk reduction in incident CVD (HR, 0.88; 95%CI, 0.79-0.99). No further benefits were observed beyond 400 MET-min/d. CONCLUSIONS: Our results support a nonlinear inverse relationship between moderate-vigorous LTPA and CVD and mortality. Benefits of PA are already observed with low levels of activity, with a maximum benefit around 3 to 5 times the current recommendations.

18.
PLoS Genet ; 16(4): e1008629, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32282858

RESUMO

Analyzing 12,361 all-cause cirrhosis cases and 790,095 controls from eight cohorts, we identify a common missense variant in the Mitochondrial Amidoxime Reducing Component 1 gene (MARC1 p.A165T) that associates with protection from all-cause cirrhosis (OR 0.91, p = 2.3*10-11). This same variant also associates with lower levels of hepatic fat on computed tomographic imaging and lower odds of physician-diagnosed fatty liver as well as lower blood levels of alanine transaminase (-0.025 SD, 3.7*10-43), alkaline phosphatase (-0.025 SD, 1.2*10-37), total cholesterol (-0.030 SD, p = 1.9*10-36) and LDL cholesterol (-0.027 SD, p = 5.1*10-30) levels. We identified a series of additional MARC1 alleles (low-frequency missense p.M187K and rare protein-truncating p.R200Ter) that also associated with lower cholesterol levels, liver enzyme levels and reduced risk of cirrhosis (0 cirrhosis cases for 238 R200Ter carriers versus 17,046 cases of cirrhosis among 759,027 non-carriers, p = 0.04) suggesting that deficiency of the MARC1 enzyme may lower blood cholesterol levels and protect against cirrhosis.


Assuntos
Fígado Gorduroso/genética , Fígado Gorduroso/prevenção & controle , Predisposição Genética para Doença , Cirrose Hepática/genética , Cirrose Hepática/prevenção & controle , Proteínas Mitocondriais/genética , Mutação de Sentido Incorreto/genética , Oxirredutases/genética , Alelos , LDL-Colesterol/sangue , Doença da Artéria Coronariana/genética , Conjuntos de Dados como Assunto , Fígado Gorduroso/sangue , Fígado Gorduroso/enzimologia , Feminino , Homozigoto , Humanos , Fígado/enzimologia , Cirrose Hepática/sangue , Cirrose Hepática/enzimologia , Cirrose Hepática Alcoólica/sangue , Cirrose Hepática Alcoólica/enzimologia , Cirrose Hepática Alcoólica/genética , Cirrose Hepática Alcoólica/prevenção & controle , Mutação com Perda de Função/genética , Masculino , Pessoa de Meia-Idade
19.
Am J Cardiol ; 125(11): 1745-1748, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32284175

RESUMO

Advanced interatrial block (A-IAB) has been associated to atrial fibrillation (AF) and ischemic stroke, raising the question as to whether such patients, even when still in sinus rhythm without documented AF, could benefit from oral anticoagulation. AF and A-IAB are both markers of stroke. The anatomical substrate in both is fibrotic atrial cardiomyopathy, resulting in atrial electromechanical dyssynchrony, dysfunction, and left atrial remodelling, that favour blood stasis and hypercoagulation. Under these conditions thrombogenic cascade may be triggered, resulting in systemic embolization. Before proposing oral anticoagulation in the management of selected patients with A-IAB, as is currently recommended in patients with AF and high CHA2DS2-Vasc score, a randomized clinical trial will have to demonstrate efficacy and safety of anticoagulation in this setting. In the meantime, an individualized approach may be considered based on the recognition of those patients at a higher risk of stroke. These may be elderly patients with A-IAB and several risk factors and, thus, with a high CHA2DS2-Vasc score and the presence of environmental arrhythmias.


Assuntos
Fibrilação Atrial/epidemiologia , Bloqueio Interatrial/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/fisiopatologia , Remodelamento Atrial/fisiologia , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Fibrose , Átrios do Coração/patologia , Humanos , Bloqueio Interatrial/complicações , Bloqueio Interatrial/fisiopatologia , Índice de Gravidade de Doença , Acidente Vascular Cerebral/prevenção & controle , Trombofilia/fisiopatologia
20.
J Am Heart Assoc ; 9(8): e015299, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32308120

RESUMO

Background Epigenome-wide association studies for cardiometabolic risk factors have discovered multiple loci associated with incident cardiovascular disease (CVD). However, few studies have sought to directly optimize a predictor of CVD risk. Furthermore, it is challenging to train multivariate models across multiple studies in the presence of study- or batch effects. Methods and Results Here, we analyzed existing DNA methylation data collected using the Illumina HumanMethylation450 microarray to create a predictor of CVD risk across 3 cohorts: Women's Health Initiative, Framingham Heart Study Offspring Cohort, and Lothian Birth Cohorts. We trained Cox proportional hazards-based elastic net regressions for incident CVD separately in each cohort and used a recently introduced cross-study learning approach to integrate these individual scores into an ensemble predictor. The methylation-based risk score was associated with CVD time-to-event in a held-out fraction of the Framingham data set (hazard ratio per SD=1.28, 95% CI, 1.10-1.50) and predicted myocardial infarction status in the independent REGICOR (Girona Heart Registry) data set (odds ratio per SD=2.14, 95% CI, 1.58-2.89). These associations remained after adjustment for traditional cardiovascular risk factors and were similar to those from elastic net models trained on a directly merged data set. Additionally, we investigated interactions between the methylation-based risk score and both genetic and biochemical CVD risk, showing preliminary evidence of an enhanced performance in those with less traditional risk factor elevation. Conclusions This investigation provides proof-of-concept for a genome-wide, CVD-specific epigenomic risk score and suggests that DNA methylation data may enable the discovery of high-risk individuals who would be missed by alternative risk metrics.

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