Beatriz López-Melgar

Prevalence, Vascular Distribution, and Multiterritorial Extent of Subclinical Atherosclerosis in a Middle-Aged Cohort The PESA (Progression of Early Subclinical Atherosclerosis) Study

Background— Data are limited on the presence, distribution, and extent of subclinical atherosclerosis in middle-aged populations. Methods and Results— The PESA (Progression of Early Subclinical Atherosclerosis) study prospectively enrolled 4184 asymptomatic participants 40 to 54 years of age (mean age, 45.8 years; 63% male) to evaluate the systemic extent of atherosclerosis in the carotid, abdominal aortic, and iliofemoral territories by 2-/3-dimensional ultrasound and coronary artery calcification by computed tomography. The extent of subclinical atherosclerosis, defined as presence of plaque or coronary artery calcification ≥1, was classified as focal (1 site affected), intermediate (2–3 sites), or generalized (4–6 sites) after exploration of each vascular site (right/left carotids, aorta, right/left iliofemorals, and coronary arteries). Subclinical atherosclerosis was present in 63% of participants (71% of men, 48% of women). Intermediate and generalized atherosclerosis was identified in 41%. Plaques were most common in the iliofemorals (44%), followed by the carotids (31%) and aorta (25%), whereas coronary artery calcification was present in 18%. Among participants with low Framingham Heart Study (FHS) 10-year risk, subclinical disease was detected in 58%, with intermediate or generalized disease in 36%. When longer-term risk was assessed (30-year FHS), 83% of participants at high risk had atherosclerosis, with 66% classified as intermediate or generalized. Conclusions— Subclinical atherosclerosis was highly prevalent in this middle-aged cohort, with nearly half of the participants classified as having intermediate or generalized disease. Most participants at high FHS risk had subclinical disease; however, extensive atherosclerosis was also present in a substantial number of low-risk individuals, suggesting added value of imaging for diagnosis and prevention. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01410318.

Long-term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: results from the METOCARD-CNIC trial (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction)

OBJECTIVESnThe goal of this trial was to study the long-term effects of intravenous (IV) metoprolol administration before reperfusion on left ventricular (LV) function and clinical events.nnnBACKGROUNDnEarly IV metoprolol during ST-segment elevation myocardial infarction (STEMI) has been shown to reduce infarct size when used in conjunction with primary percutaneous coronary intervention (pPCI).nnnMETHODSnThe METOCARD-CNIC (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction) trial recruited 270 patients with Killip class ≤II anterior STEMI presenting early after symptom onset (<6 h) and randomized them to pre-reperfusion IV metoprolol or control group. Long-term magnetic resonance imaging (MRI) was performed on 202 patients (101 per group) 6 months after STEMI. Patients had a minimal 12-month clinical follow-up.nnnRESULTSnLeft ventricular ejection fraction (LVEF) at the 6 months MRI was higher after IV metoprolol (48.7 ± 9.9% vs. 45.0 ± 11.7% in control subjects; adjusted treatment effect 3.49%; 95% confidence interval [CI]: 0.44% to 6.55%; p = 0.025). The occurrence of severely depressed LVEF (≤35%) at 6 months was significantly lower in patients treated with IV metoprolol (11% vs. 27%, p = 0.006). The proportion of patients fulfilling Class I indications for an implantable cardioverter-defibrillator (ICD) was significantly lower in the IV metoprolol group (7% vs. 20%, p = 0.012). At a median follow-up of 2 years, occurrence of the pre-specified composite of death, heart failure admission, reinfarction, and malignant arrhythmias was 10.8% in the IV metoprolol group versus 18.3% in the control group, adjusted hazard ratio (HR): 0.55; 95% CI: 0.26 to 1.04; p = 0.065. Heart failure admission was significantly lower in the IV metoprolol group (HR: 0.32; 95% CI: 0.015 to 0.95; p = 0.046).nnnCONCLUSIONSnIn patients with anterior Killip class ≤II STEMI undergoing pPCI, early IV metoprolol before reperfusion resulted in higher long-term LVEF, reduced incidence of severe LV systolic dysfunction and ICD indications, and fewer heart failure admissions. (Effect of METOprolol in CARDioproteCtioN During an Acute Myocardial InfarCtion. The METOCARD-CNIC Trial; NCT01311700).

Long term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: results from the METOCARD-CNIC trial.

OBJECTIVESnThe goal of this trial was to study the long-term effects of intravenous (IV) metoprolol administration before reperfusion on left ventricular (LV) function and clinical events.nnnBACKGROUNDnEarly IV metoprolol during ST-segment elevation myocardial infarction (STEMI) has been shown to reduce infarct size when used in conjunction with primary percutaneous coronary intervention (pPCI).nnnMETHODSnThe METOCARD-CNIC (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction) trial recruited 270 patients with Killip class ≤II anterior STEMI presenting early after symptom onset (<6 h) and randomized them to pre-reperfusion IV metoprolol or control group. Long-term magnetic resonance imaging (MRI) was performed on 202 patients (101 per group) 6 months after STEMI. Patients had a minimal 12-month clinical follow-up.nnnRESULTSnLeft ventricular ejection fraction (LVEF) at the 6 months MRI was higher after IV metoprolol (48.7 ± 9.9% vs. 45.0 ± 11.7% in control subjects; adjusted treatment effect 3.49%; 95% confidence interval [CI]: 0.44% to 6.55%; p = 0.025). The occurrence of severely depressed LVEF (≤35%) at 6 months was significantly lower in patients treated with IV metoprolol (11% vs. 27%, p = 0.006). The proportion of patients fulfilling Class I indications for an implantable cardioverter-defibrillator (ICD) was significantly lower in the IV metoprolol group (7% vs. 20%, p = 0.012). At a median follow-up of 2 years, occurrence of the pre-specified composite of death, heart failure admission, reinfarction, and malignant arrhythmias was 10.8% in the IV metoprolol group versus 18.3% in the control group, adjusted hazard ratio (HR): 0.55; 95% CI: 0.26 to 1.04; p = 0.065. Heart failure admission was significantly lower in the IV metoprolol group (HR: 0.32; 95% CI: 0.015 to 0.95; p = 0.046).nnnCONCLUSIONSnIn patients with anterior Killip class ≤II STEMI undergoing pPCI, early IV metoprolol before reperfusion resulted in higher long-term LVEF, reduced incidence of severe LV systolic dysfunction and ICD indications, and fewer heart failure admissions. (Effect of METOprolol in CARDioproteCtioN During an Acute Myocardial InfarCtion. The METOCARD-CNIC Trial; NCT01311700).

The Progression and Early detection of Subclinical Atherosclerosis (PESA) study: rationale and design.

BACKGROUNDnThe presence of subclinical atherosclerosis is a likely predictor of cardiovascular events; however, factors associated with the early stages and progression of atherosclerosis are poorly defined.nnnOBJECTIVEnThe PESA study examines the presence of subclinical atherosclerosis by means of noninvasive imaging and prospectively analyzes the determinants associated with its development and progression in a middle-aged population.nnnMETHODSnThe PESA study is an observational, longitudinal and prospective cohort study in a target population of 4000 healthy subjects (40-54 years old, 35% women) based in Madrid (Spain). Recruitment began in June 2010 and will be completed by the end of 2013. Baseline examination consists of (1) assessment for cardiovascular risk factors (including lifestyle and psychosocial factors); (2) screening for subclinical atherosclerosis using 2D/3D ultrasound in carotid, abdominal aorta and iliofemoral arteries, and coronary artery calcium score (CACS) by computed tomography; and (3) blood sampling for determination of traditional risk factors, advanced omics and biobanking. In addition, a subgroup of 1300 participants with evidence of atherosclerosis on 2D/3D ultrasound or CACS will undergo a combined (18)F-fluorodeoxyglucose-positron emission tomography/magnetic resonance imaging ((18)FDG PET/MRI) study of carotid and iliofemoral arteries. Follow-up at 3 and 6 years will include a repetition of baseline measurements, except for the (18)FDG PET/MRI study, which will be repeated at 6 years.nnnCONCLUSIONSnThe PESA study is expected to identify new imaging and biological factors associated with the presence and progression of atherosclerosis in asymptomatic people and will help to establish a more personalized management of medical care.

Normal LDL-Cholesterol Levels Are Associated With Subclinical Atherosclerosis in the Absence of Risk Factors

BACKGROUNDnAbsence of cardiovascular risk factors (CVRFs) is traditionally considered low risk for atherosclerosis; however, individuals without CVRFs, as currently defined, still have events.nnnOBJECTIVESnThis study sought to identify predictors of subclinical atherosclerosis in CVRF-free individuals.nnnMETHODSnParticipants from the PESA (Progression of Early Subclinical Atherosclerosis) study (nxa0=xa04,184) without conventional CVRFs were evaluated (nxa0=xa01,779; 45.0 ± 4.1 years, 50.3% women). CVRF freedom was defined as no current smoking and untreated blood pressurexa0<140/90xa0mmxa0Hg, fasting glucosexa0<126xa0mg/dl, total cholesterolxa0<240xa0mg/dl, low-density lipoprotein cholesterol (LDL-C)xa0<160xa0mg/dl, and high-density lipoprotein cholesterolxa0≥40xa0mg/dl. Axa0subgroupxa0with optimal CVRFs (nxa0=xa0740) was also defined as having blood pressurexa0<120/80xa0mmxa0Hg, fasting glucosexa0<100xa0mg/dl, glycosylated hemoglobin <5.7%, and total cholesterolxa0<200xa0mg/dl. We evaluated ultrasound-detected carotid, iliofemoral, and abdominal aortic plaques; coronary artery calcification; serum biomarkers; and lifestyle. Adjusted odds ratios (with 95% confidence interval) and ordinal logistic regression models were used.nnnRESULTSnSubclinical atherosclerosis (plaque or coronary artery calcification) was present in 49.7% of CVRF-free participants. Together with male sex and age, LDL-C was independently associated with atherosclerosis presence and extent, in both the CVRF-free and CVRF-optimal groups (odds ratio [×10xa0mg/dl]: 1.14 to 1.18; pxa0< 0.01 for all). Atherosclerosis presence and extent was also associated in the CVRF-free group with glycosylated hemoglobin levels.nnnCONCLUSIONSnMany CVRF-free middle-aged individuals have atherosclerosis. LDL-C, even at levels currently considered normal, is independently associated with the presence and extent of early systemic atherosclerosis in the absence of major CVRFs. These findings support more effective LDL-C lowering for primordial prevention, even in individualsxa0conventionally considered at optimal risk. (Progression of Early Subclinical Atherosclerosis [PESA] Study; NCT01410318).

Impact of the Timing of Metoprolol Administration During STEMI on Infarct Size and Ventricular Function

BACKGROUNDnPre-reperfusion administration of intravenous (IV) metoprolol reduces infarct size in ST-segment elevation myocardial infarction (STEMI).nnnOBJECTIVESnThis study sought to determine how this cardioprotective effect is influenced by the timing of metoprolol therapy having either a long or short metoprolol bolus-to-reperfusion interval.nnnMETHODSnWe performed a post hoc analysis of the METOCARD-CNIC (effect of METOprolol of CARDioproteCtioN during an acute myocardial InfarCtion) trial, which randomized anterior STEMI patients to IV metoprolol or control before mechanical reperfusion. Treated patients were divided into short- and long-interval groups, split by the median time from 15 mg metoprolol bolus to reperfusion. We also performed a controlled validation study in 51 pigs subjected to 45 min ischemia/reperfusion. Pigs were allocated to IV metoprolol with a long (-25 min) or short (-5 min) pre-perfusion interval, IV metoprolol post-reperfusion (+60 min), or IV vehicle. Cardiac magnetic resonance (CMR) was performed inxa0the acute and chronic phases in both clinical and experimental settings.nnnRESULTSnFor 218 patients (105 receiving IV metoprolol), the median time from 15 mg metoprolol bolus to reperfusion was 53 min. Compared with patients in the short-interval group, those with longer metoprolol exposure had smaller infarcts (22.9xa0gxa0vs. 28.1 g; pxa0= 0.06) and higher left ventricular ejection fraction (LVEF) (48.3% vs. 43.9%; pxa0= 0.019) on day 5xa0CMR. These differences occurred despite total ischemic time being significantly longer in the long-interval group (214xa0min vs. 160 min; pxa0< 0.001). There was no between-group difference in the time from symptom onset to metoprolol bolus. In the animal study, the long-interval group (IV metoprolol 25 min before reperfusion) had the smallest infarcts (day 7 CMR) and highest long-term LVEF (day 45 CMR).nnnCONCLUSIONSnIn anterior STEMI patients undergoing primary angioplasty, the sooner IV metoprolol is administered in the course of infarction, the smaller the infarct and the higher the LVEF. These hypothesis-generating clinical data are supported by a dedicated experimental large animal study.

The Importance of Breakfast in Atherosclerosis Disease: Insights From the PESA Study

BACKGROUNDnDaily habits, including the number and quality of eating occasions, are potential targets for primary prevention strategies with large health impacts. Skipping breakfast is considered a frequent and unhealthy habit associated with an increased cardiovascular (CV) risk.nnnOBJECTIVESnThe study sought to explore the association between different breakfast patterns and CV risk factors and the presence, distribution, and extension of subclinical atherosclerosis.nnnMETHODSnCross-sectional analysis was performed within the PESA (Progression of Early Subclinical Atherosclerosis) study, a prospective cohort of asymptomatic (free of CV events at baseline) adults 40 to 54 years of age. Lifestyle and multivascular imaging data along with clinical covariates were collected from 4,052 participants. Multivariate logistic regression models were used in the analysis.nnnRESULTSnThree patterns of breakfast consumption were studied: high-energy breakfast, when contributing to >20% of total daily energy intake (27% of the population); low-energy breakfast, when contributing between 5% and 20% of total daily energy intake (70% of the population); and skipping breakfast, when consumingxa0<5% of total daily energy (3% of the population). Independent of the presence of traditional and dietary CV risk factors, and compared with high-energy breakfast, habitual skipping breakfast was associated with a higher prevalence of noncoronary (odds ratio: 1.55; 95% confidence interval: 0.97 to 2.46) and generalized (odds ratio: 2.57; 95% confidence interval: 1.54 to 4.31) atherosclerosis.nnnCONCLUSIONnSkipping breakfast is associated with an increased odds of prevalent noncoronary and generalized atherosclerosis independently of the presence of conventional CV risk factors. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318).

Subclinical Atherosclerosis Burden by 3D Ultrasound in Mid-Life: The PESA Study

BACKGROUNDnDetection of subclinical atherosclerosis improves risk prediction beyond cardiovascular risk factors (CVRFs) and risk scores, but quantification of plaque burden may improve it further. Novel 3-dimensional vascular ultrasound (3DVUS) provides accurate volumetric quantification of plaque burden.nnnOBJECTIVESnThe authors evaluated associations between 3DVUS-based plaque burden and CVRFs and explored potential added value over simple plaque detection.nnnMETHODSnThe authors included 3,860 (92.2%) PESA (Progression of Early Subclinical Atherosclerosis) study participants (age 45.8 ± 4.3 years; 63% men). Bilateral carotid and femoral territories were explored by 3DVUS to determine the number of plaques and territories affected, and to quantify global plaque burden defined as the sum of all plaque volumes. Linear regression and proportional odds models were used to evaluate associations of plaque burden with CVRFs and estimated 10-year cardiovascular risk.nnnRESULTSnPlaque burden was higher in men (63.4xa0mm3 [interquartile range (IQR): 23.8 to 144.8xa0mm3] vs. 25.7xa0mm3 [IQR:xa011.5 to 61.6xa0mm3] in women; pxa0< 0.001), in the femoral territory (64xa0mm3 [IQR: 27.6 to 140.5xa0mm3] vs. 23.1xa0mm3 [IQR: 9.9 to 48.7xa0mm3] in the carotid territory; pxa0< 0.001), and with increasing age (pxa0< 0.001). Age, sex, smoking, and dyslipidemia were more strongly associated with femoral than with carotid disease burden, whereas hypertension and diabetes showed no territorial differences. Plaque burden was directly associated with estimated cardiovascular risk independently of the number of plaques or territories affected (pxa0< 0.01).nnnCONCLUSIONSn3DVUS quantifies higher plaque burden in men, in the femoral territory, and with increasing age during midlife. Plaque burden correlates strongly with CVRFs, especially at the femoral level, and reflects estimated cardiovascular risk more closely than plaque detection alone. (Progression of Early Subclinical Atherosclerosis [PESA] Study; NCT01410318).

Association Between a Social-Business Eating Pattern and Early Asymptomatic Atherosclerosis.

BACKGROUNDnThe importance of a healthy diet in relation to cardiovascular health promotion is widely recognized. Identifying specific dietary patterns related to early atherosclerosis would contribute greatly to inform effective primary prevention strategies.nnnOBJECTIVESnThis study sought to quantify the association between specific dietary patterns and presence and extent of subclinical atherosclerosis in a population of asymptomatic middle-aged adults.nnnMETHODSnThe PESA (Progression of Early Subclinical Atherosclerosis) study enrolled 4,082 asymptomatic participants 40 to 54 years of age (mean age 45.8 years; 63% male) to evaluate the presence of subclinical atherosclerosis in multiple vascular territories. A fundamental objective of this cohort study was to evaluate the life-style-related determinants, including diet, on atherosclerosis onset and development. We conducted a cross-sectional analysis of baseline data, including detailed information on dietary habits obtained as part of the overall life-style and risk factor assessment, as well as a complete vascular imaging study that was performed blinded to the clinical information.nnnRESULTSnMost PESA participants follow a Mediterranean (40% of participants) or a Western (41%) dietary pattern. A new pattern, identified among 19% of participants, was labeled as a social-business eating pattern, characterized by a high consumption of red meat, pre-made foods, snacks, alcohol, and sugar-sweetened beverages and frequent eating-out behavior. Participants following this pattern presented a significantly worse cardiovascular risk profile and, after adjustment for risk factors, increased odds of presenting subclinical atherosclerosis (odds ratio: 1.31; 95% confidence interval: 1.06 to 1.63) compared with participants following a Mediterranean diet.nnnCONCLUSIONSnA new social-business eating pattern, characterized by high consumption of red and processed meat,xa0alcohol, and sugar-sweetened beverages, and by frequent snacking and eating out as part of an overall unhealthy life-style, is associated with an increased prevalence, burden, and multisite presence of subclinical atherosclerosis. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318).

Cardiovascular imaging: what have we learned from animal models?

Cardiovascular imaging has become an indispensable tool for patient diagnosis and follow up. Probably the wide clinical applications of imaging are due to the possibility of a detailed and high quality description and quantification of cardiovascular system structure and function. Also phenomena that involve complex physiological mechanisms and biochemical pathways, such as inflammation and ischemia, can be visualized in a non-destructive way. The widespread use and evolution of imaging would not have been possible without animal studies. Animal models have allowed for instance, (i) the technical development of different imaging tools, (ii) to test hypothesis generated from human studies and finally, (iii) to evaluate the translational relevance assessment of in vitro and ex-vivo results. In this review, we will critically describe the contribution of animal models to the use of biomedical imaging in cardiovascular medicine. We will discuss the characteristics of the most frequent models used in/for imaging studies. We will cover the major findings of animal studies focused in the cardiovascular use of the repeatedly used imaging techniques in clinical practice and experimental studies. We will also describe the physiological findings and/or learning processes for imaging applications coming from models of the most common cardiovascular diseases. In these diseases, imaging research using animals has allowed the study of aspects such as: ventricular size, shape, global function, and wall thickening, local myocardial function, myocardial perfusion, metabolism and energetic assessment, infarct quantification, vascular lesion characterization, myocardial fiber structure, and myocardial calcium uptake. Finally we will discuss the limitations and future of imaging research with animal models.