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BACKGROUND: Conventional low-density lipoprotein cholesterol (LDL-C) quantification includes cholesterol attributable to lipoprotein(a) (Lp(a)-C) due to their overlapping densities. OBJECTIVES: The purposes of this study were to compare the association between LDL-C and LDL-C corrected for Lp(a)-C (LDLLp(a)corr) with incident coronary heart disease (CHD) in the general population and to investigate whether concomitant Lp(a) values influence the association of LDL-C or apolipoprotein B (apoB) with coronary events. METHODS: Among 68,748 CHD-free subjects at baseline LDLLp(a)corr was calculated as "LDL-C-Lp(a)-C," where Lp(a)-C was 30% or 17.3% of total Lp(a) mass. Fine and Gray competing risk-adjusted models were applied for the association between the outcome incident CHD and: 1) LDL-C and LDLLp(a)corr in the total sample; and 2) LDL-C and apoB after stratification by Lp(a) mass (≥/<90th percentile). RESULTS: Similar risk estimates for incident CHD were found for LDL-C and LDL-CLp(a)corr30 or LDL-CLp(a)corr17.3 (subdistribution HR with 95% CI) were 2.73 (95% CI: 2.34-3.20) vs 2.51 (95% CI: 2.15-2.93) vs 2.64 (95% CI: 2.26-3.10), respectively (top vs bottom fifth; fully adjusted models). Categorization by Lp(a) mass resulted in higher subdistribution HRs for uncorrected LDL-C and incident CHD at Lp(a) ≥90th percentile (4.38 [95% CI: 2.08-9.22]) vs 2.60 [95% CI: 2.21-3.07]) at Lp(a) <90th percentile (top vs bottom fifth; Pinteraction0.39). In contrast, apoB risk estimates were lower in subjects with higher Lp(a) mass (2.43 [95% CI: 1.34-4.40]) than in Lp(a) <90th percentile (3.34 [95% CI: 2.78-4.01]) (Pinteraction0.49). CONCLUSIONS: Correction of LDL-C for its Lp(a)-C content provided no meaningful information on CHD-risk estimation at the population level. Simple categorization of Lp(a) mass (≥/<90th percentile) influenced the association between LDL-C or apoB with future CHD mostly at higher Lp(a) levels.
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Apolipoproteínas B , LDL-Colesterol , Enfermedad Coronaria , Lipoproteína(a) , Humanos , Lipoproteína(a)/sangre , LDL-Colesterol/sangre , Masculino , Femenino , Enfermedad Coronaria/sangre , Enfermedad Coronaria/epidemiología , Persona de Mediana Edad , Apolipoproteínas B/sangre , Anciano , Adulto , Factores de Riesgo , Medición de Riesgo/métodos , IncidenciaRESUMEN
BACKGROUND: Lipids, including phospholipids and bile acids, exert various signaling effects and are thought to contribute to the development of coronary artery disease (CAD). Here, we aimed to compare lipidomic and bile acid profiles in the blood of patients with and without CAD stratified by sex. METHODS: From 2015 to 2022, 3,012 patients who underwent coronary angiography were recruited in the INTERCATH cohort. From the overall cohort, subgroups were defined using patient characteristics such as CAD vs. no CAD, 1st vs. 3rd tertile of LDL-c, and female vs. male sex. Hereafter, a matching algorithm based on age, BMI, hypertension status, diabetes mellitus status, smoking status, the Mediterranean diet score, and the intake of statins, triglycerides, HDL-c and hs-CRP in a 1:1 ratio was implemented. Lipidomic analyses of stored blood samples using the Lipidyzer platform (SCIEX) and bile acid analysis using liquid chromatography with tandem mass spectrometry (LCâMS/MS) were carried out. RESULTS: A total of 177 matched individuals were analyzed; the median ages were 73.5 years (25th and 75th percentile: 64.1, 78.2) and 71.9 years (65.7, 77.2) for females and males with CAD, respectively, and 67.6 years (58.3, 75.3) and 69.2 years (59.8, 76.8) for females and males without CAD, respectively. Further baseline characteristics, including cardiovascular risk factors, were balanced between the groups. Women with CAD had decreased levels of phosphatidylcholine and diacylglycerol, while no differences in bile acid profiles were detected in comparison to those of female patients without CAD. In contrast, in male patients with CAD, decreased concentrations of the secondary bile acid species glycolithocholic and lithocholic acid, as well as altered levels of specific lipids, were detected compared to those in males without CAD. Notably, male patients with low LDL-c and CAD had significantly greater concentrations of various phospholipid species, particularly plasmalogens, compared to those in high LDL-c subgroup. CONCLUSIONS: We present hypothesis-generating data on sex-specific lipidomic patterns and bile acid profiles in CAD patients. The data suggest that altered lipid and bile acid composition might contribute to CAD development and/or progression, helping to understand the different disease trajectories of CAD in women and men. REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04936438 , Unique identifier: NCT04936438.
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Ácidos y Sales Biliares , Enfermedad de la Arteria Coronaria , Lipidómica , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ácidos y Sales Biliares/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/sangre , Caracteres Sexuales , Factores Sexuales , Espectrometría de Masas en Tándem , Triglicéridos/sangre , Estudios de CohortesRESUMEN
PURPOSE OF REVIEW: This article focuses on pharmacological agents as well as dietary changes aimed at the reduction of the inflammatory burden measured by circulating C-reactive protein concentrations. RECENT FINDINGS: Over the last years, repurposed as well as new anti-inflammatory agents have been investigated in outcome trials in the cardiovascular field. Currently, a specific inhibition of the inflammatory cascade via the interleukin-6 ligand antibody ziltivekimab is being explored in large-scale outcome trials, after the efficacy of this agent with regard to the reduction of inflammatory biomarkers was proven recently. Next to the investigated pharmacological agents, specific dietary patterns possess the ability to improve the inflammatory burden. This enables patients themselves to unlock a potential health benefit ahead of the initiation of a specific medication targeting the inflammatory pathway. SUMMARY: Both pharmacological agents as well as diet provide the opportunity to improve the inflammatory profile and thereby lower C-reactive protein concentrations. Whilst advances in the field of specific anti-inflammatory treatments have been made over the last years, their broad implementation is currently limited. Therefore, optimization of diet (and other lifestyle factors) could provide a cost effective and side-effect free intervention to target low-grade vascular inflammation.
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Proteína C-Reactiva , Dieta , Inflamación , Humanos , Proteína C-Reactiva/metabolismo , Inflamación/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacologíaRESUMEN
OBJECTIVE: This study aimed to determine if there is an increased risk of incident cardiovascular diseases (CVD) resulting from cumulative night shift work in the German population-based Gutenberg Health Study (GHS). METHODS: We examined working participants of the GHS at baseline and after five years. Cumulative night shift work in the 10 years before baseline was assessed and categorized as low (1-220 nights â up to 1 year), middle (221-660 nights â 1-3 years), and high (>660 nights â more than 3 years) night shift exposure. Hazard ratios (HR) were estimated for incident "quality-assured CVD events" using Cox proportional hazard models. RESULTS: At baseline, 1092 of 8167 working participants performed night shift work. During the follow-up, 202 incident cardiovascular events occurred. The crude incidence rates for CVD per 1000 person-years were 6.88 [95% confidence interval (CI) 4.80-9.55] for night shift workers and 5.19 (95% CI 4.44-6.04) for day workers. Cumulative incidence curves showed a higher cumulative incidence in workers exposed to night shift work compared to day workers after five years. The adjusted HR for incident CVD events were 1.26 (95% CI 0.68-2.33), 1.37 (95% CI 0.74-2.53) and 1.19 (95% CI 0.67-2.12) for employees in the low, middle and high night shift categories compared to employees without night shift work, respectively. CONCLUSIONS: The observed tendencies indicate that night shift work might be negatively associated with cardiovascular health. We expect the continued follow-up will clarify the long-term impact of night shift work.
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Enfermedades Cardiovasculares , Horario de Trabajo por Turnos , Humanos , Horario de Trabajo por Turnos/efectos adversos , Enfermedades Cardiovasculares/epidemiología , Tolerancia al Trabajo Programado , Estudios de Seguimiento , Factores de Riesgo , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
BACKGROUND AND AIMS: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population. METHODS: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.8/13.8 years, respectively). Fine and Gray competing risk-adjusted models were calculated according to accompanying hsCRP concentration (<2 and ≥2â mg/L). RESULTS: Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted sub-distribution hazard ratios [sHRs (95% confidence interval)] for the highest vs. lowest fifth of Lp(a) distribution were 1.45 (1.23-1.72) and 1.48 (1.23-1.78) for a hsCRP group of <2 and ≥2â mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (Pinteraction = 0.82). In those with established CHD, similar associations were seen only among individuals with hsCRP ≥ 2â mg/L [1.34 (1.03-1.76)], whereas among participants with a hsCRP concentration <2â mg/L, there was no clear association between Lp(a) and future CHD events [1.29 (0.98-1.71)] (highest vs. lowest fifth, fully adjusted models; Pinteraction = 0.024). CONCLUSIONS: While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of high-risk patients for forthcoming Lp(a)-targeting compounds.
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Proteína C-Reactiva , Enfermedad Coronaria , Humanos , Proteína C-Reactiva/metabolismo , Estudios Prospectivos , Factores de Riesgo , Lipoproteína(a) , Enfermedad Coronaria/epidemiología , Biomarcadores/metabolismoRESUMEN
The inflammatory burden as measured by high-sensitivity C-reactive Protein (hsCRP) is recognized as a cardiovascular risk factor, which can however be affected by lifestyle-related risk factors (LRF). Up-to-date the interplay between hsCRP, LRF and presence and extent of atherosclerotic disease is still largely unknown, which we therefore sought to investigate in a contemporary population-based cohort. We included participants from the cross-sectional population-based Hamburg City Health Study. Affected vascular beds were defined as coronary, peripheral, and cerebrovascular arteries. LRF considered were lack of physical activity, overweight, active smoking and poor adherence to a Mediterranean diet. We computed multivariable analyses with hsCRP as the dependent variable and LRF as covariates according to the number of vascular beds affected. In the 6765 individuals available for analysis, we found a stepwise increase of hsCRP concentration both according to the number of LRF present as well as the number of vascular beds affected. Adjusted regression analyses showed an independent association between increasing numbers of LRF with hsCRP levels across the extent of atherosclerosis. We demonstrate increasing hsCRP concentrations according to both the number of LRF as well as the extent of atherosclerosis, emphasizing the necessity of lifestyle-related risk factor optimization.
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Aterosclerosis , Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria , Humanos , Proteína C-Reactiva/metabolismo , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedades Cardiovasculares/etiología , Estudios de Cohortes , Estudios Transversales , Aterosclerosis/epidemiología , Aterosclerosis/etiología , Factores de Riesgo , Estilo de Vida , BiomarcadoresRESUMEN
PURPOSE OF REVIEW: The purpose of this review is to critically discuss whether more aggressive lipid-lowering strategies are needed in patients with acute coronary syndromes (ACS). RECENT FINDINGS: Currently, available data on early (in-hospital/discharge) administration of potent lipid-lowering drugs, such as proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in patients during the vulnerable post-ACS phase, have clearly demonstrated clinical efficacy of the "strike early and strike strong" approach not only for rapid reduction of low-density lipoprotein cholesterol (LDL-C) to unprecedentedly low levels, but also for associated favorable composition of coronary plaque. Intensive lipid-lowering therapy with rapid achievement of the LDL-C treatment goal in ACS patients seems reasonable. However, whether such profound LDL-C reduction would result in additional benefit on the reduction of future CV events still has to be established. Thus, data addressing CV outcomes in such vulnerable patients at extreme CV risk are urgently needed.
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Síndrome Coronario Agudo , Anticolesterolemiantes , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Proproteína Convertasa 9 , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Síndrome Coronario Agudo/tratamiento farmacológico , LDL-Colesterol , Hipolipemiantes/uso terapéutico , Anticolesterolemiantes/uso terapéuticoRESUMEN
BACKGROUND: The sodium-glucose co-transporter 2 inhibitor empagliflozin improves cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM) and heart failure. Experimental studies suggest a direct cardiac effect of empagliflozin associated with an improvement in left ventricular diastolic function. METHODS: In the randomized, double-blind, two-armed, placebo-controlled, parallel group trial EmDia, patients with T2DM and elevated left ventricular E/E´ ratio were enrolled and randomized 1:1 to receive empagliflozin 10 mg/day versus placebo. The primary endpoint was the change of left ventricular E/E´ ratio after 12 weeks of intervention. RESULTS: A total of 144 patients with T2DM and an elevated left ventricular E/e´ ratio (age 68.9 ± 7.7 years; 14.1% women; E/e´ ratio 9.61[8.24/11.14], left ventricular ejection fraction 58.9% ± 5.6%). After 12 weeks of intervention, empagliflozin resulted in a significant higher decrease in the primary endpoint E/e´ ratio by - 1.18 ([95% confidence interval (CI) - 1.72/- 0.65]; P < 0.0001) compared with placebo. The beneficial effect of empagliflozin was consistent across all subgroups and also occurred in subjects with heart failure and preserved ejection fraction (n = 30). Additional effects of empagliflozin on body weight, HbA1c, uric acid, red blood cell count, hemoglobin, mean corpuscular hemoglobin, and hematocrit were detected (all P < 0.001). Approximately one-third of the reduction in E/e´ by empagliflozin could be explained by the variables examined. CONCLUSIONS: Empagliflozin improves diastolic function in patients with T2DM and elevated end-diastolic pressure. Since the positive effects were consistent in patients with and without heart failure with preserved ejection fraction, the data add a mechanistic insight for the beneficial cardiovascular effect of empagliflozin. TRIAL REGISTRATION: Clinicaltrials.gov, unique identifier: NCT02932436.
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Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Función Ventricular Izquierda , Volumen Sistólico , Resultado del Tratamiento , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Método Doble Ciego , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/complicacionesRESUMEN
AIMS: To investigate the predictive ability of direct plasma renin and aldosterone concentrations as well as their ratio [aldosterone-to-renin (ARR)] for incident hypertension in the general population. METHODS AND RESULTS: Concentration of renin and aldosterone were measured by a chemiluminescence immunoassay using the fully automated LIAISON® platform (DiaSorin) among 5362 participants of the population-based Gutenberg Health Study, who were normotensive and had no clinically overt cardiovascular disease at baseline. During a follow-up period of 5 years, 18.6% (n = 996) developed a new-onset hypertension. Comparing extreme quartiles of biomarker distribution, the relative risk (RR) for incident arterial hypertension was found to be 1.58 [95% confidence interval (CI) 1.25-2.00; P = 0.00015; Q1 vs. Q4ref] for renin; 1.29 (95% CI 1.05-1.59, P = 0.018; Q4 vs. Q1ref) for aldosterone and 1.70 (95% CI 1.33-2.12; P < 0.0001; Q4 vs. Q1ref) for ARR after multivariable adjustment in men. In females, only high ARR was independently predictive for incident hypertension over 5 years [RR 1.29 (95% CI 1.04-1.62); P = 0.024]. Even in the subgroup of individuals having biomarker concentrations within the reference range, high ARR was predictive for new-onset hypertension in men [RR 1.44 (95% CI 1.13-1.83); P = 0.003]. Finally, synergistic effects of co-prevalent obesity and ARR on incident hypertension were also demonstrated, resulting in markedly higher risk estimates as seen for biomarker alone [RR of 2.70 (95% CI 2.05-3.6) for Q4 of ARR and having body mass index ≥ 30 kg/m2 vs. low ARR (Q1ref) and normal weight; P < 0.0001]. CONCLUSION: Among normotensives from the general population ARR possesses a stronger predictive value for incident hypertension than renin or aldosterone alone. The prediction of arterial hypertension by ARR was even stronger in obese subjects.
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Aldosterona , Hipertensión , Masculino , Femenino , Humanos , Renina , Hipertensión/diagnóstico , Hipertensión/epidemiología , Presión Sanguínea , BiomarcadoresRESUMEN
BACKGROUND: Cigarette smoking is a threat to global human health and a leading cause of the cardiovascular disease (CVD) morbidity and mortality. Importantly, sex-specific differences in smoking-induced arterial stiffness, an early key event in the development of atherosclerotic CVD, remain still elusive. Thus, this study sought out to investigate sex-specific associations between smoking and measures of arterial stiffness. METHODS AND RESULTS: Overall, 15,010 participants (7584 men and 7426 women aged 35-74 years) of the Gutenberg Health Study were examined at baseline during 2007-2012. Smoking status, pack-years of smoking, and years since quitting smoking were assessed by a standardized computer-assisted interview. Arterial stiffness and wave reflection were determined by stiffness index (SI) and augmentation index (AI). In the total sample, 45.8% had never smoked, 34.7% were former smokers, and 19.4% were current smokers. Median cumulative smoking exposure was 22.0 pack-years in current male smokers and 16.0 in current female smokers. In general, multivariable linear regression models adjusted for a comprehensive set of confounders revealed that smoking status, pack-years of smoking, and years since quitting smoking were dose-dependently associated with markers of arterial stiffness. In sex-specific analyses, these associations were overall more pronounced in men and SI was stronger related to the male sex, whereas differences between men and women in the case of AI appeared to be less substantial. DISCUSSION: The present results indicate that chronic smoking is strongly and dose-dependently associated with increased arterial stiffness in a large population-based cohort regardless of sex but with a stronger association in men.
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Aterosclerosis , Enfermedades Cardiovasculares , Fumar Cigarrillos , Rigidez Vascular , Femenino , Humanos , Masculino , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Fumar Cigarrillos/efectos adversos , Fumar Cigarrillos/epidemiología , Modelos Lineales , Adulto , Persona de Mediana Edad , AncianoRESUMEN
Familial hypercholesterolemia (FH), a condition, which is characterized by a life-long exposure to markedly elevated low-density lipoprotein (LDL) concentrations from birth, and it still remains underdiagnosed and undertreated, despite the fact that its heterogeneous form represents one of the commonest genetic disorders to date. Indeed, only 10% of all estimated affected individuals have been diagnosed worldwide and for the most of them diagnosis comes too late, when atherosclerotic cardiovascular disease (ASCVD) has already been developed. Undiagnosed and undertreated FH leads to accelerated ASCVD with a high rate of premature deaths. Recently, several novel treatment modalities have been introduced, especially for the management of severe hypercholesterolemia. Nonetheless, a substantial number of FH patients still do not achieve guideline-recommended LDL cholesterol target values. In the present review we will summarize and critically discuss pitfalls and challenges in successful diagnosis and treatment of FH.
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Objective: The current study was undertaken to prospectively explore whether having low levels of von Willebrand factor (vWF) antigen and vWF activity reduce the risk for cardiovascular disease and death. Methods: VWF antigen and vWF activity were measured by enzyme-linked immunosorbent assay and an immunological-based assay, respectively, in a subsample of 4857 individuals aged between 35 and 74 years old, enrolled between April 2007 and October 2008 in the population-based Gutenberg Health Study. VWF antigen and activity below the 20th percentile was set as a measure of "low vWF." Adjusted robust Poisson regression models were used to analyze the relation between low vWF and the incidence of cardiovascular disease (CVD). Consequent adjusted cox regression models as well as cumulative incidence plots were calculated to explore the relation between all-cause and cardiovascular mortality and low vWF. Results: VWF activity levels <20th percentile (i.e., <76.2%) were associated with a decreased relative risk for CVD (RR: 0.59, 95% CI: 0.37-0.95), despite adjusting for age and sex. After adjusting for levels of F-VIII, the association persisted (RR: 0.60, 95% CI: 0.36-0.99). The cumulative incidence plots demonstrated that vWF antigen <20th percentile significantly correlated with decreased cardiovascular mortality. VWF antigen<20th percentile (i.e., <83%) was significantly associated with lower risk of all-cause mortality, despite adjusting for clinical factors (RR: 61, 95% CI: 0.41-0.91). Conclusion: The study demonstrated that having low vWF activity levels were associated with a lower risk for CVD. Additionally, it revealed a decreased risk of cardiovascular and all-cause mortality in individuals with low levels of vWF antigen, shining new light on vWF as a potential target for novel therapies.
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PURPOSE OF REVIEW: Treatment of dyslipidemia represents one of the most crucial strategies to reduce risk of atherosclerotic cardiovascular (CV) disease (ASCVD). In this review, we critically summarize our knowledge on emerging cholesterol-lowering therapy, targeting PCSK9, paying particular attention on treatment allocation of two drug groups, currently available for clinical use, namely, anti-PCSK9 monoclonal antibodies (mAbs) and inclisiran, a first-in-class small interfering RNA against PCSK9. RECENT FINDINGS: Although both drug classes show a pronounced, but fairly similar reduction in LDL-cholesterol, their long-term safety is still unknown. Compared to mAbs, inclisiran has a more favorable dosing regimen with biannual application that might improve therapeutic adherence significantly. However, a CV outcome trial (CVOT) for inclisiran is still missing. If inclisiran will be safe and effective in ongoing/future CVOTs, it has a huge potential to overcome medication non-compliance, thereby providing a powerful therapeutic option to decrease the burden of ASCVD.
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Anticuerpos Monoclonales , Colesterol , Humanos , Selección de Paciente , Anticuerpos Monoclonales/uso terapéutico , ARN Interferente Pequeño/uso terapéutico , Proproteína Convertasa 9RESUMEN
BACKGROUND: The current study aims to identify the relationships between coagulation factors and plasma thrombin generation in a large population-based study by comparing individuals with a history of arterial or venous thrombosis to cardiovascular healthy individuals. METHODS: This study comprised 502 individuals with a history of arterial disease, 195 with history of venous thrombosis and 1402 cardiovascular healthy individuals (reference group) from the population-based Gutenberg Health Study (GHS). Calibrated Automated Thrombography was assessed and coagulation factors were measured by means of BCS XP Systems. To assess the biochemical determinants of TG variables, a multiple linear regression analysis, adjusted for age, sex and antithrombotic therapy, was conducted. RESULTS: The lag time, the time to form the first thrombin, was mainly positively associated with the natural coagulant and anti-coagulant factors in the reference group, i.e. higher factors result in a longer lag time. The same determinants were negative for individuals with a history of arterial or venous thrombosis, with a 10 times higher effect size. Endogenous thrombin potential, or area under the curve, was predominantly positively determined by factor II, VIII, X and IX in all groups. However, the effect sizes of the reported associations were 4 times higher for the arterial and venous disease groups in comparison to the reference group. CONCLUSION: This large-scale analysis demonstrated a stronger effect of the coagulant and natural anti-coagulant factors on the thrombin potential in individuals with a history of arterial or venous thrombosis as compared to healthy individuals, which implicates sustained alterations in the plasma coagulome in subjects with a history of thrombotic vascular disease, despite intake of antithrombotic therapy.
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Patients with atherosclerotic cardiovascular disease have a high risk for subsequent cardiovascular events despite optimal drug treatment including statins and ezetimibe. Dyslipidemia represents a central and direct cause of this, with a frequent failure to achieve the target values recommended in the guidelines. New lipid-lowering substances are increasingly becoming available for treatment of this residual risk. Due to their high cost, cost-effectiveness analyses are required in order to justify their use. Important variables when considering the cost-effectiveness of a drug are quality adjusted life years (QALY) and the incremental cost-effectiveness ratio (ICER). The lower bounds of the ICER determining the cost-effectiveness of a treatment vary between healthcare systems. The proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors alirocumab and evolocumab are deemed to be cost-effective particularly in patients with high levels of low-density lipoprotein cholesterol (LDL-C) prior to treatment or with a high cardiovascular risk as determined by the presence of defined risk criteria. Similar considerations apply to the PCSK9 small interfering RNA (siRNA) inclisiran. Administration of bempedoic acid is deemed cost-effective especially in patients with statin intolerance. Eicosapentaenoic acid is deemed cost-effective overall, although the data with respect to the exact placebo-controlled efficacy are still inconclusive.
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Anticolesterolemiantes , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Anticuerpos Monoclonales/efectos adversos , Anticolesterolemiantes/farmacología , Anticolesterolemiantes/uso terapéutico , LDL-Colesterol , Análisis Costo-Beneficio , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inhibidores de PCSK9 , Proproteína Convertasa 9/metabolismoRESUMEN
AIMS: Evidence suggests that peripheral vascular function is related to cardiovascular disease (CVD) and mortality. We evaluated the associations of non-invasive measures of flow-mediated dilatation and peripheral arterial tonometry with incident CVD and mortality. METHODS AND RESULTS: In a post-hoc analysis of the community-based Gutenberg Health Study, median age 55 years (25th/75th percentile 46/65) and 49.5% women, we measured brachial artery flow-mediated dilatation (N=12 599) and fingertip peripheral arterial tonometry (N=11 125). After a follow-up of up to 11.7 years, we observed 595 incident CVD events, 106 cardiac deaths, and 860 deaths in total. Survival curves showed decreased event-free survival with higher mean brachial artery diameter and baseline pulse amplitude and better survival with higher mean flow-mediated dilatation and peripheral arterial tonometry ratio (all Plog rank <0.05). In multivariable-adjusted Cox regression analyses only baseline pulse amplitude was inversely related to mortality [hazard ratio (HR) per standard deviation increase, 0.86, 95% confidence interval (95% CI), 0.79-0.94; P=0.0009]. After exclusion of individuals with prevalent CVD the association was no longer statistically significant in multivariable-adjusted models (HR 0.91, 95% CI 0.81-1.02; P=0.11). None of the vascular variables substantially increased the C-index of a model comprising clinical risk factors. CONCLUSIONS: In our cohort, non-invasive measures of peripheral vascular structure and function did not reveal clinically relevant associations with incident CVD or mortality. Whether determination of pulse amplitude by peripheral arterial tonometry improves clinical decision-making in primary prevention needs to be demonstrated.
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Enfermedades Cardiovasculares , Rigidez Vascular , Arteria Braquial , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Estudios de Cohortes , Endotelio Vascular , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
AIMS: To assess the prevalence of type 2 diabetes mellitus (T2DM) and prediabetes in the general population and to investigate the associated cardiovascular burden and clinical outcome. METHODS AND RESULTS: The study sample comprised 15,010 individuals aged 35-74 years of the population-based Gutenberg Health Study. Subjects were classified into euglycaemia, prediabetes and T2DM according to clinical and metabolic (HbA1c) information. The prevalence of prediabetes was 9.5% (n = 1415) and of T2DM 8.9% (n = 1316). Prediabetes and T2DM showed a significantly increased prevalence ratio (PR) for age, obesity, active smoking, dyslipidemia, and arterial hypertension compared to euglycaemia (for all, P < 0.0001). In a robust Poisson regression analysis, prediabetes was established as an independent predictor of clinically-prevalent cardiovascular disease (PRprediabetes 1.20, 95% CI 1.07-1.35, P = 0.002) and represented as a risk factor for asymptomatic cardiovascular organ damage independent of traditional risk factors (PR 1.04, 95% CI 1.01-1.08, P = 0.025). Prediabetes was associated with a 1.5-fold increased 10-year risk for cardiovascular disease compared to euglycaemia. In Cox regression analysis, prediabetes (HR 2.10, 95% CI 1.76-2.51, P < 0.0001) and T2DM (HR 4.28, 95% CI 3.73-4.92, P < 0.0001) indicated for an increased risk of death. After adjustment for age, sex and traditional cardiovascular risk factors, only T2DM (HR 1.89, 95% CI 1.63-2.20, P < 0.0001) remained independently associated with increased all-cause mortality. CONCLUSION: Besides T2DM, also prediabetes inherits a significant cardiovascular burden, which translates into poor clinical outcome and indicates the need for new concepts regarding the prevention of cardiometabolic disorders.
Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Estado Prediabético/complicaciones , Adulto , Anciano , Enfermedades Cardiovasculares/etiología , Femenino , Alemania/epidemiología , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Masculino , Persona de Mediana Edad , Distribución de Poisson , Prevalencia , Estudios ProspectivosRESUMEN
PURPOSE OF REVIEW: To briefly summarize recently published evidence on the possible therapeutic modulation of inflammatory processes in atherosclerotic cardiovascular disease (ASCVD), focusing on the rationale for an additional randomized clinical trial, targeting both persistently elevated cholesterol and inflammatory residual risk and critically discuss still open issues and future perspectives with regard to treatment allocation. RECENT FINDINGS: Several large-scale clinical trials over the past few years have advanced our understanding of the role of inflammation in atherosclerosis, demonstrating that targeting the NLRP3 inflammasome and the IL-1ß pathway indeed represent a new avenue to reduce residual risk in patients with ASCVD. However, despite optimal lipid-lowering therapy and novel options to modulate residual inflammatory risk, there are still a large number of individuals, being at high risk for recurrent ASCVD events. SUMMARY: The integration of a dual target strategy aimed at lowering the inflammatory burden in combination with aggressive lipid-modifying for those at high/very high ASCVD risk may hold potential to significantly improve patient care. However, a number of questions related to the design of such 2â×â2 factorial trial still needs to be answered.