Role of cardiovascular magnetic resonance in the prognosis of patients with myocardial infarction with non-obstructive coronary arteries.

BACKGROUND: It is estimated that 5% to 10% of patients with myocardial infarction (MI) present with no obstructive coronary artery lesions. Until now, most studies have focused on acute coronary syndrome, including different clinical entities with a similar presentation encompassed under the term MINOCA (MI with non-obstructive coronary arteries). The aim of this study is to assess the prognosis of patients diagnosed with true infarction, confirmed by cardiovascular magnetic resonance (CMR), in the absence of significant coronary lesions. METHODS: Prospective multicenter registry study, including 120 consecutive patients with a CMR-confirmed MI without obstructive coronary artery lesions. The primary clinical outcome was major adverse cardiovascular events (MACE: death, non-fatal infarction, stroke, or cardiac readmission), assessed over three years. RESULTS: Seventy-six patients (63.3%) were admitted with a diagnosis of acute coronary syndrome, and 44 (36.6%) for other causes (mainly heart failure); the definitive diagnosis was established by CMR. Most patients (64.2%) were men, and the mean age was 58.8 ± 13.5 years. Patients presented with small infarcts: 83 (69.1%) showed late gadolinium enhancement (LGE) in one or two myocardial segments, mainly transmural (in 77.5% of patients) and with a preserved left ventricular ejection fraction (median 54.8%, interquartile range 37-62). The most frequent infarct location was inferolateral (n = 38, 31.7%). During follow-up, 43 patients (35.8%) experienced a MACE, including 9 (7.5%) who died. In multivariable analysis, LGE in two versus one myocardial segment doubled the risk of adverse cardiac events (hazard ratio [HR] 2.32, 95% confidence interval [CI] 0.97-5.83, p = 0.058). Involvement of three or more myocardial segments almost tripled the risk (HR 2.71, 95% CI 1.04-7.04, p = 0.040 respectively). CONCLUSIONS: Patients with true MI but without significant coronary artery lesions predominantly had small infarcts. Myocardial 3-segment LGE involvement is associated with a significantly higher risk of adverse cardiac events.

Inflammatory status and uricaemia determine HDL-cholesterol levels in hypertensive adults over 65: an analysis of the FAPRES register.

In inflammatory disease, the levels of high-density lipoprotein cholesterol (HDL-C) decrease, and the composition of HLD-C changes. Data from the "non-inflammatory" general population indicate the presence of the same phenomenon, albeit to a smaller extent. Levels of uricaemia contribute to the overall inflammatory state of patients. The aim of this study was to analyse the association between inflammatory state, levels of uricaemia, and levels of HLD-C in a hypertensive Spanish population aged 65 or older. This was a retrospective analysis of the FAPRES database. We compared lipid levels [HDL-C, low-density lipoprotein cholesterol (LDL-C), total cholesterol, and triglycerides] in terciles of patients according to their leukocyte counts and uricaemia. When we observed statistically significant differences at a 95% confidence level, we constructed a multivariable linear regression model to adjust for possible confounders. We analysed 860 patients (52.7% women) with a mean age of 72.9 years (±5.8). Participants in the highest tercile for leukocytes or uricaemia presented with significantly lower levels of HDL-C and higher levels of triglycerides, but there was no difference in total cholesterol or LDL-C. The multivariable analysis confirmed an independent and inverse association between HDL-C and both leukocytes (ß = -0.001, p = 0.025) and uricaemia (ß = -1.054, p = 0037) as well as an independent, direct association between triglycerides and both leukocytes (ß = 0.004, p = 0.049), and uricaemia (ß = 8.411, p = 0.003). In hypertensive adults aged 65 or older, inflammatory state, and uricaemia independently operate to decrease HDL-C-these findings confirm those described in studies in people with inflammatory disease. This phenomenon could help to define a proatherogenic profile in people without inflammatory disease.

[Use of the CHADS2 score as a predictor of the risk of mortality in hypertensive patients. The FAPRES study]. / Uso de la escala CHADS2 como predictor de riesgo de mortalidad en pacientes hipertensos. El estudio FAPRES.

FOUNDATIONS AND AIM: The aim of this study is to analyze the CHADS2 score as a marker of the risk of mortality in hypertensive patients, with and without the presence of atrial fibrillation. METHODS: We included 1,003 hypertensive patients≥65 years. Risk factors, and CHADS2 score were recorded among other factors, as well as clinical follow-up of number and type of deaths. RESULTS: Mean age was 72.8±5.8 years, and 47.5% were men. During follow-up there were 41 deaths, 20 were of cardiovascular origin. Patients with higher CHADS2 had a higher mortality: 1.5% CHADS2=1; 4.7% in CHADS2=2; 9.1% in CHADS2=3, and 7.8% in CHADS2≥4. CONCLUSIONS: The CHADS2 score can be a clinical instrument of easy application to identify hypertensive patients with a high risk of mortality.

The CHADS2 Score to Predict Stroke Risk in the Absence of Atrial Fibrillation in Hypertensive Patients Aged 65 Years or Older.

INTRODUCTION AND OBJECTIVES: The CHADS2 score is a proven, essential tool for estimating cardioembolic risk (mainly stroke) in patients with nonvalvular atrial fibrillation, with the purpose of determining the indication for anticoagulant therapy. In this study we analyzed the use of CHADS2 in hypertensive patients without known atrial fibrillation in a Mediterranean population. METHODS: The study included 887 hypertensive patients aged 65 years or older without atrial fibrillation or anticoagulant therapy, who attended a medical consultation. Data on the patients' main risk factors, cardiovascular history, and medication were collected, basic laboratory analyses and electrocardiography were performed, and the CHADS2 score (heart failure, hypertension, age ≥ 75 years, diabetes mellitus, and previous stroke or transient ischemic attack) was calculated. A clinical follow-up was carried out, recording hospital admissions for a stroke or transient ischemic attack. The median duration of follow-up was 804 days. RESULTS: Mean age was 72.5 (SD,5.7) years, 46.6% were men, 27.8% had diabetes, and 8.6% were smokers. During follow-up, 40 patients were hospitalized for a stroke or transient ischemic attack (4.5%). The event-free survival analysis showed significant differences according to the CHADS2 score (log rank test, P < .001). On multivariate analysis, smoking and CHADS2 ≥3 were independent predictors of stroke or transient ischemic attack. CONCLUSIONS: The CHADS2 may be useful for estimating the risk of stroke or transient ischemic attack in hypertensive patients without known atrial fibrillation.

Gender differences related to the presence of atrial fibrillation in older hypertensive patients.

AIM: To determine whether there are gender differences in the epidemiological profile of atrial fibrillation (AF) and to characterise the clinical, biochemical, and therapeutic factors associated with AF. METHODS: Each investigator (primary care physicians or physicians based in hospital units for hypertension treatment) recruited the first 3 patients with an age of ≥ 65 years and a clinical diagnosis of hypertension (ambulatory blood pressure monitoring and an electrocardiogram, were performed) on the first working day of the week for 5 wk and identified those individuals with atrial fibrillation. A binary logistic regression was performed, including all of the variables that were significant in the univariate analysis, to establish the variables that were associated with the presence of arrhythmia. RESULTS: A total of 1028 patients were included in the study, with a mean age of 72.8 ± 5.8 years. Of these patients, 47.3% were male, 9% were smokers, 27.6% were diabetics, 48.3% had dyslipidaemia, 10.9% had angina, and 6.5% had experienced a myocardial infarction. Regarding gender differences, the men exhibited a larger waist circumference, a lower body mass index, less obesity, and a more extensive history of diabetes, smoking, ischaemic heart disease, kidney failure, peripheral arterial disease and carotid disease than the women. There were no differences, however, in the prevalence of AF between the men and the women (11.5% vs 9.2%, respectively; P = no significant). Regarding treatment, the women received antiplatelet agents and diuretics less frequently, but there were no other differences in the use of antihypertensive and antithrombotic therapies. In the multivariate analysis, AF in the total study population was associated with age, alcohol consumption, the presence of heart disease, and decreased glomerular filtration. In the women, AF was associated with all of the factors included in the overall analysis, as well as the presence of left ventricle hypertrophy. In contrast, in the men, the only risk factors associated with AF were age, the presence of heart disease and alcohol consumption. CONCLUSION: In patients with hypertension over 65 years of age, there are relevant gender differences in the factors associated with AF.

Circulating biomarkers of collagen metabolism in arterial hypertension: relevance of target organ damage.

OBJECTIVE: Increasing experimental evidence indicates that alterations in the extracellular matrix are implicated in hypertension and its chronic complications. Selected markers of extracellular matrix metabolism were investigated as potential biomarkers for hypertensive remodelling and correlated with the severity and extent of target organ damage (TOD) in patients with essential hypertension. METHODS: We studied 159 consecutive patients being treated for essential hypertension. An exhaustive evaluation of the heart, kidney and blood vessel damage was performed, and plasma levels of plasma procollagen type I (PICP), matrix metalloproteinase-1 (MMP-1) and its inhibitor (tissue inhibitor metalloproteinase-1, TIMP-1) were determined. Patients were categorized into four groups: no TOD (33 patients), level 1 TOD (52 patients), level 2 TOD (44 patients) and level 3 TOD (30 patients). RESULTS: The serum levels of MMP-1 and TIMP-1 were higher in patients with TOD than in hypertensive patients without TOD. Increasing levels of these molecules were progressively associated with an increase in the number of organs damaged, with highest levels of markers in patients with level 3 TOD (heart, kidney and blood vessels). There were no differences in PICP levels between groups. We found a slight but significant correlation between TIMP-1 and all hypertensive organ damage. Logistic regression analysis showed that age, smoking, diabetes mellitus, abdominal perimeter, MMP-1 and TIMP-1 were independently related to the level of TOD. CONCLUSION: Circulating concentration of MMP-1 and TIMP-1 is associated with an extended hypertensive disease, with more TOD. TIMP-1 may have a role as a biomarker of total remodelling burden in hypertensive patients.

Inflammation and apoptosis in hypertension. Relevance of the extent of target organ damage.

INTRODUCTION AND OBJECTIVES: To investigate the relationship between inflammatory and apoptotic parameters and the severity and extent of target organ damage in patients with essential hypertension. METHODS: We studied 159 consecutive patients with treated essential hypertension. An exhaustive evaluation of damage to heart, kidney, and blood vessels was performed and plasma levels of inflammatory (interleukin 6 and soluble receptor of tumor necrosis factor-alpha type 2) and apoptotic markers (soluble receptor of tumor necrosis factor-alpha type 1 and soluble Fas receptor) were determined. Patients were categorized into four groups: a) no organ damage (33 patients); b) 1 organ damaged (52 patients); c) 2 organs damaged (44 patients), and d) 3 organs damaged (30 patients). RESULTS: Serum levels of interleukin 6, soluble receptor of tumor necrosis factor-alpha type 1 and soluble receptor of tumor necrosis factor-alpha type 2 were higher in patients with target organ damage than in hypertensive patients without organ damage. Increasing levels of these molecules were progressively associated with an increase in the number of organs damaged, and the highest levels were observed in the group with damage to 3 organs (heart, kidney, and blood vessels). There were no differences in soluble Fas receptor levels between groups. Logistic regression analysis showed that age, smoking, diabetes mellitus, abdominal circumference, interleukin 6, and soluble receptor of tumor necrosis factor-alpha type 1 were independently related to the number of target organs damaged. CONCLUSIONS: Extensive hypertensive disease with involvement of more target organs was associated with greater inflammatory and apoptotic activation in these hypertensive patients.

Carotid resistive index in treated hypertensive patients: relationship with target organ damage.

AIM: The resistive index (RI) is a hemodynamic parameter that reflects local wall extensibility and related vascular resistance. We analyze the relationship between common carotid RI and target organ damage in treated hypertensive patients. METHODS: We analyzed 265 consecutive hypertensive patients. Risk factors, cardiovascular history and treatments were collected; blood test, urinary albumin excretion (UAE), echocardiography to determine left ventricular mass index (LVMI), ankle-brachial index (ABI) and carotid echo-Doppler ultrasound to calculate the carotid intima-media thickness (IMT) and RI of both common carotids arteries were performed. RESULTS: A positive correlation was found between carotid RI and age, systolic blood pressure, heart rate, carotid IMT, LVMI, UAE and a negative correlation was found with diastolic blood pressure and ABI. Subjects at the top quartile of carotid RI showed a higher prevalence of left ventricular hypertrophy and peripheral artery disease (increased IMT, carotid plaques and lower ABI) compared with those with low RI (p < 0.05). Multiple regression analysis demonstrated that age, systolic and diastolic blood pressure and LVMI independently influence carotid RI. CONCLUSION: Carotid RI is related with age, systolic-diastolic blood pressure and LVMI in hypertensive patient. This evaluation could predict the presence of early cardiovascular damage and provide an accurate estimation of overall risk in this population.

[Impact of blood pressure control on the ankle-brachial index in hypertensive patients]. / Impacto del control de las cifras de presión arterial sobre el índice tobillo-brazo en el paciente hipertenso.

BACKGROUND AND OBJECTIVE: The guidelines for arterial hypertension recommend a systematic determination of ankle-brachial index (ABI) in the initial risk stratification in hypertensive patients, while not indicating whether controls should be evolutionary. Our aim was to analyze the evolution of the ABI value in hypertensive patients in terms of control of blood pressure (BP) after one year follow-up. PATIENTS AND METHODS: We included 209 hypertensive patients, in whom ABI was determined at baseline and after one year of antihypertensive treatment. Patients were divided into 2 groups in terms of good/poor clinical control of BP (<140/90 mmHg). RESULTS: A total of 82.8% of the population showed a good control of the BP after one year of treatment and it was associated with significant increase in the ABI value (1.081 versus 1.046 at baseline, P=.002). By contrast, there was no difference of ABI value in patients with poor BP control (1.054 versus 1.093 at baseline). CONCLUSIONS: A good clinical control of BP is associated with an increase in the value of the ABI.

Variability of NT-proBNP and its relationship with inflammatory status in patients with stable essential hypertension: a 2-year follow-up study.

BACKGROUND: The variability of NT-proBNP levels has been studied in heart failure, yet no data exist on these changes over time in hypertensive patients. Furthermore, studies on the relationship between natriuretic peptides and inflammatory status are limited. METHODOLOGY/PRINCIPAL FINDINGS: 220 clinically and functionally asymptomatic stable patients (age 59 ± 13, 120 male) out of 252 patients with essential hypertension were followed up, and NT-proBNP was measured at baseline, 12 and 24 months. No differences in NT-proBNP were found with respect to the basal stage in the hypertrophic group, but significant changes were found in non-hypertrophic subjects. The reproducibility of NT-proBNP measurements was better in patients with hypertrophy than in the non-hypertrophic group for the three intervals (stage I-basal; stage II-stage I; stage II-basal) with a reference change value of 34%, 35% and 41%, respectively, in the hypertrophic group. A more elevated coefficient of correlation was obtained in the hypertrophic group than in patients without hypertrophy: basal versus stage I (r = 0.79, p < 0.0001 and r = 0.59, p < 0.0001) and stage I versus stage II (r = 0.86, p < 0.0001 and r = 0.56, p < 0.0001). Finally, levels of NT-proBNP significantly correlated with sTNF-R1 (p < 0.0001) and IL-6 (p < 0.01) during follow-up. A multivariate linear regression analysis showed that sTNF-R1 is an independent factor of NT-proBNP. CONCLUSIONS/SIGNIFICANCE: This work shows that there is good stability in NT-proBNP levels in a follow-up study of asymptomatic patients with stable hypertension and left ventricular hypertrophy. As a consequence, assessment of NT-proBNP concentrations may be a useful tool for monitoring the follow-up of hypertensive patients with hypertrophy. Measured variations in peptide levels, exceeding 35% in a 12-month follow-up and 41% in a 24-month follow-up, may indicate an increase in cardiovascular risk, and therefore implies adjustment in the medical treatment. In addition, this study shows a link between neurohormonal and inflammatory activation in these patients.

Prognostic significance of heart rate in hospitalized patients presenting with myocardial infarction.

AIM: To investigate the prognostic significance of resting heart rate in patients with acute coronary syndrome (ACS), independent of other known factors. METHODS: Patients 40 years of age or older who had been admitted with acute coronary syndrome (ACS) to one of the 94 hospitals participating in the Prevalence of Peripheral Arterial Disease in Patients with Acute Coronary Syndrome (PAMISCA) study were included. Patients were divided into two groups based on their resting heart rate (HR ≥ or < 70 bpm). Complications were recording during a follow-up period of 1 year. RESULTS: There were 1054 ACS patients analyzed (43.5% with ST segment elevation and 56.5% without elevation). Mean age was 66.6 ± 11.7 years, 70.6% were male and 29.4% of subjects were female. During follow-up, more patients in the HR ≥ 70 bpm group were hospitalized for heart failure and they also had a higher mortality rate. In the multivariate analysis, a heart rate of ≥ 70 bpm was independently related to overall mortality during the follow-up period (hazard ratio 2.5; 95% confidence interval, 1.26-4.97, P = 0.009). CONCLUSION: A resting heart rate ≥ 70 bpm in patients who survive an ACS is an indicator of a high risk of suffering cardiovascular events during follow-up.

Impact of cardiovascular risk factors and inflammatory status on urinary 8-OHdG in essential hypertension.

BACKGROUND: The urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) reflect the oxidation status of hypertensive subjects and it can be used for monitoring oxidative stress changes. However, the influence of cardiovascular risk factors and inflammation on the urinary levels of this marker in hypertension (HT) has never evaluated. The purpose of this study was to analyze the impact of cardiovascular risk factors, and established inflammatory markers on 8-OHdG in essential HT. METHODS: We studied 149 asymptomatic hypertensive patients (61 ± 14 years). A routine physical examination, laboratory analyses, and echo-Doppler study were performed. Urinary 8-OHdG and plasma tumor necrosis factor-α (TNF-α), soluble TNF receptor 1 (sTNF-R1), soluble TNF receptor 2 (sTNF-R2), and interleukin-6 (IL-6) were determined. RESULTS: 8-OHdG/creatinine levels were higher in hypertrophic patients (P = 0.022) and correlated with left ventricular mass index (P < 0.01). When 8-OHdG/creatinine was compared according to obesity and diabetes in our hypertensive subjects, no significant differences were found. 8-OHdG/creatinine was increased in hypertensive smokers (P = 0.032) and women (P = 0.006). Furthermore, 8-OHdG/creatinine correlated with TNF-α, sTNF-R1, sTNF-R2 (P < 0.0001), and with IL-6 (P < 0.05). A multivariate linear regression analysis showed that gender, smoking, and TNF-α were independent factors of 8-OHdG/creatinine. CONCLUSIONS: Urinary 8-OHdG was increased in hypertensive patients with hypertrophy even under medical treatment. The presence of other cardiovascular risk factors on top of HT do not alter the concentrations of this oxidative stress marker, only smoking increasing its levels. TNF-α is an independent factor of 8-OHdG. These data suggest that this urinary marker gives specific additional information, further than blood pressure control alone, when evaluating hypertensive patients.

[Diagnostic accuracy of NT-proBNP compared with electrocardiography in detecting left ventricular hypertrophy of hypertensive origin]. / Validez diagnóstica del NT-proBNP frente al electrocardiograma en la detección de hipertrofia ventricular izquierda de origen hipertensivo.

Electrocardiography (ECG) is the most widely used method for diagnosing left ventricular hypertrophy (LVH) in hypertensive patients. We assessed the value of N-terminal pro-brain natriuretic peptide (NT-proBNP) determination compared with ECG for detecting LVH in 336 consecutive hypertensive patients with preserved systolic function. We found a significant correlation between NT-proBNP levels and left ventricular mass adjusted for body surface area (r=.41; P<.001). The area under the receiver operating characteristic curve was 0.75 (95% CI, 0.7-0.8). A cut-off of 74.2 pg/mL had a greater sensitivity than ECG (76.6% vs 25.5%; P<.001) and a higher negative predictive value (87.8% vs 76.6%; P<.001) in the identification of LVH. NT-proBNP determination may be a useful tool for LVH screening in hypertensive patients.

Pathological ankle-brachial index is equivalent of advanced age in acute coronary syndromes.

BACKGROUND: Age is one the factors associated with poor prognosis in acute coronary syndromes (ACS) and elderly patients are a high-risk collective with few parameters for mid-term cardiovascular stratification. We aimed to assess the predictive value of ankle-brachial index (ABI) in patients (> 75 years) for 1-year mortality after an ACS. MATERIALS AND METHODS: Prospective, observational and multicentre study of ACS patients in whom ABI was assessed during hospitalization. RESULTS: A total of 1·054 patients were included, mean age 66·6 (11·7) years from whom 26·6% were > 75 years. Elderly patients showed more history of cardiovascular disease and higher prevalence of all risk factors, except current smoking. Angiography and revascularization were performed less frequently in the elderly. Patients > 75 years showed higher presence of three vessel coronary disease and received fewer guideline-recommended treatments. Patients who died through the follow-up, mean time 387·9 ± 7·2 days, had lower ABI (0·73 ± 0·24 vs. 0·92 ± 0·22; P < 0·01), also in the elderly patients (0·73 ± 0·24 vs. 0·86 ± 0·23; P < 0·01). Cox regression analysis identified age > 75 years (HR: 2·30; IC 95% 1·26-4·18; P < 0·01) and ABI < 0·90 (HR: 3·58; IC 95% 1·80-7·15; P < 0·01) as risk factors for to 1-year mortality. Mortality was similar in elderly patients with ABI > 0·90 and young patients with ABI < 0·90; the worst prognosis was observed in elderly patients with ABI < 0·90 (HR: 10·01; 95% CI 3·74-27·15). CONCLUSIONS: Elderly patients represent a relevant collective of patients with ACS and are treated less optimally. ABI predicts 1-year mortality after an ACS in elderly patients.

[What measure of carotid wall thickening is the best atherosclerotic loading score in the hypertensive patient: maximum or mean value?]. / ¿Qué medida del grosor íntima-media carotídeo caracteriza mejor la carga aterosclerótica del paciente hipertenso: valor máximo o medio?

Recent guidelines on arterial hypertension regard increased carotid intima-media thickness (IMT) as a marker of end-organ damage. However, these guidelines do not specify whether the maximum or mean IMT should be used as an indicator. The aim of this study was to compare these two measures and their relationship to atherosclerotic burden. The study involved 215 consecutive hypertensive patients who were divided into three groups according to their IMT: maximum IMT>0.9mm (with mean IMT<0.9mm); mean IMT>0.9mm (i.e. mean and maximum IMT>0.9mm); and normal IMT. Patients with a pathologically raised IMT (whether maximum or mean value) were more likely to be dyslipidemic, were older, had a longer history of hypertension, and had a poorer glomerular filtration rate and ankle-brachial index. Patients with a mean IMT>0.9mm were more likely to have carotid plaque, carotid stenosis and a low ankle-brachial index than those with a maximum IMT>0.9mm. The mean IMT provided a better indication of atherosclerotic burden in patients with hypertension.

Combination of ankle brachial index and diabetes mellitus to predict cardiovascular events and mortality after an acute coronary syndrome.

OBJECTIVE: Diabetes mellitus and low ankle brachial index (ABI) are both conditions associated with an increased cardiovascular risk. In the setting of an acute coronary syndrome (ACS), diabetes is associated with increased mortality, but little is known regarding a low ABI. The aim of the study was to evaluate the prevalence of diabetes and low ABI in patients after an ACS and their prognostic value. METHODS: 1156 patients ≥40 years admitted with an ACS were screened with ABI previous to hospital discharge to investigate the presence of peripheral arterial disease (PAD) (ABI value≤0.9). 1054 were finally followed for one year. Patients were stratified according to diabetes and PAD status. The primary endpoint of the study was all-cause mortality. RESULTS: The prevalence of diabetes was 36% and PAD was 39.9%. After a median follow up of 382 days, 59 patients died (5.6%), the majority from a cardiovascular event. In both diabetic and nondiabetic patients, the presence of PAD was significantly associated with an increased incidence of the primary event. After adjustment for several prognostic variables, patients with diabetes and PAD had an increased risk of mortality (HR 4.05 (95% CI 1.86-8.83)). PAD and diabetic patients had an intermediate and similar incidence of cardiovascular events. CONCLUSIONS: Our results show that the presence of an ABI≤0.9 predicts cardiovascular risk to the same extent as diabetes, and the combination of diabetes and PAD is a powerful tool after an ACS to predict the occurrence of an adverse event.