Julio A. Chirinos

The evolution of Lemierre syndrome: Report of 2 cases and review of the literature

Lemierre syndrome (postanginal septicemia) is caused by an acute oropharyngeal infection with secondary septic thrombophlebitis of the internal jugular vein and frequent metastatic infections. A high degree of clinical suspicion is necessary for diagnosis. Fusobacterium necrophorum is the usual etiologic agent. The disease progresses in several steps. The first stage is the primary infection, which is usually a pharyngitis (87.1% of cases). This is followed by local invasion of the lateral pharyngeal space and IJV septic thrombophlebitis (documented in 71.5% of cases), and finally, the occurrence of metastatic complications (present in 90% of cases at the time of diagnosis). A sore throat is the most common symptom during the primary infection (82.5% of cases). During invasion of the lateral pharyngeal space and IJV septic thrombophlebitis, a swollen and/or tender neck is the most common finding (52.2% of patients) and should be considered a red flag in patients with current or recent pharyngitis. The most common site of metastatic infection is the lungs (79.8% of cases). In contrast to the preantibiotic era, cavitating pneumonia and septic arthritis are now uncommon. Most patients (82.5%) had fever at some stage during the course of the disease. Gastrointestinal complaints such as abdominal pain, nausea, and vomiting were common (49.5% of cases). An elevated white blood cell count occurred in 75.2% of cases. Hyperbilirubinemia with slight elevation of liver enzyme levels occurred in one-third of patients, but frank jaundice was uncommon, in contrast to its high frequency reported in the preantibiotic era. We conclude that, most likely as a consequence of widespread antibiotic use for pharyngeal infections, the typical course of the disease has changed since Lemierre’s original description. The typical triad in our series was: pharyngitis, a tender/swollen neck, and noncavitating pulmonary infiltrates. The previous classical description of severe sepsis with cavitating pneumonia and septic arthritis was not commonly seen in our review. Mortality was low in our series (6.4%), but significant morbidity occurred, which was likely preventable by early diagnosis and treatment. The pathophysiology, natural history, diagnostic methods for internal jugular vein thrombosis, and management are discussed.

Aortic Pressure Augmentation Predicts Adverse Cardiovascular Events in Patients With Established Coronary Artery Disease

Pulse pressure (PP), a marker of arterial stiffness, predicts cardiovascular risk. We aimed to determine whether augmentation pressure (AP) derived from the aortic pressure waveform predicts major adverse cardiovascular events (MACE) and death independently of PP in patients with established coronary artery disease (CAD). We prospectively followed-up 297 males undergoing coronary angiography for 1186±424 days. Ascending aortic pressure tracings obtained during catheterization were used to calculate AP (difference between the second and the first systolic peak). Augmentation index (AIx) was defined as AP as a percentage of PP. We evaluated whether AP and AIx can predict the risk of MACE (unstable angina, acute myocardial infarction, coronary revascularization, stroke, or death) and death using Cox regression. All models evaluating AP included PP to assess whether AP adds to the information already provided by PP. Both AP and AIx significantly predicted MACE. The hazard ratio (HR) per 10 mm Hg increase in AP was 1.20 (95% confidence interval [CI], 1.08 to 1.34; P<0.001); the HR for each 10% increase in AIx was 1.28 (95% CI, 1.11 to 1.48; P=0.004). After adjusting for other univariate predictors of MACE, age, and other potential confounders, AP remained a significant predictor of MACE (HR per 10 mm Hg increase=1.19; 95% CI, 1.06 to 1.34; P=0.002), as did AIx (adjusted HR, 1.28; 95% CI, 1.09 to 1.50; P=0.003). AP was a significant predictor of death (HR per 10 mm Hg increase=1.18; 95% CI, 1.02 to 1.39; P=0.03). Higher AIx was associated with a trend toward increased mortality (HR=1.22; 95% CI, 0.98 to 1.52; P=0.056). Aortic AP predicts adverse outcomes in patients with CAD independently of PP and other risk markers.

Recommendations for Improving and Standardizing Vascular Research on Arterial Stiffness: A Scientific Statement From the American Heart Association.

Much has been published in the past 20 years on the use of measurements of arterial stiffness in animal and human research studies. This summary statement was commissioned by the American Heart Association to address issues concerning the nomenclature, methodologies, utility, limitations, and gaps in knowledge in this rapidly evolving field. The following represents an executive version of the larger online-only Data Supplement and is intended to give the reader a sense of why arterial stiffness is important, how it is measured, the situations in which it has been useful, its limitations, and questions that remain to be addressed in this field. Throughout the document, pulse-wave velocity (PWV; measured in meters per second) and variations such as carotid-femoral PWV (cfPWV; measured in meters per second) are used. PWV without modification is used in the general sense of arterial stiffness. The addition of lowercase modifiers such as “cf” is used when speaking of specific segments of the arterial circulation. The ability to measure arterial stiffness has been present for many years, but the measurement was invasive in the early times. The improvement in technologies to enable repeated, minimal-risk, reproducible measures of this aspect of circulatory physiology led to its incorporation into longitudinal cohort studies spanning a variety of clinical populations, including those at extreme cardiovascular risk (patients on dialysis), those with comorbidities such as diabetes mellitus (DM) and hypertension, healthy elders, and general populations. In the ≈3 decades of clinical use of PWV measures in humans, we have learned much about the importance of this parameter. PWV has proven to have independent predictive utility when evaluated in conjunction with standard risk factors for death and cardiovascular disease (CVD). However, the field of arterial stiffness investigation, which has exploded over the past 20 years, has proliferated without logistical guidance for clinical and …

Arterial wave reflections and incident cardiovascular events and heart failure: MESA (Multiethnic Study of Atherosclerosis)

OBJECTIVES This study sought to assess the relationship between central pressure profiles and cardiovascular events (CVEs) in a large community-based sample. BACKGROUND Experimental and physiologic data mechanistically implicate wave reflections in the pathogenesis of left ventricular failure and cardiovascular disease, but their association with these outcomes in the general population is unclear. METHODS Aortic pressure waveforms were derived from a generalized transfer function applied to the radial pressure waveform recorded noninvasively from 5,960 participants in the Multiethnic Study of Atherosclerosis. The central pressure waveform was separated into forward and reflected waves using a physiologic flow waveform. Reflection magnitude (RM = [Reflected/Forward wave amplitude] × 100), augmentation index ([Second/First systolic peak] × 100) and pulse pressure amplification ([Radial/aortic pulse pressure] × 100) were assessed as predictors of CVEs and congestive heart failure (CHF) during a median follow-up of 7.61 years. RESULTS After adjustment for established risk factors, aortic AIx independently predicted hard CVEs (hazard ratio [HR] per 10% increase: 1.08; 95% confidence interval [CI]: 1.01 to 1.14; p = 0.016), whereas PPA independently predicted all CVEs (HR per 10% increase: 0.82; 95% CI: 0.70 to 0.96; p = 0.012). RM was independently predictive of all CVEs (HR per 10% increase: 1.34; 95% CI: 1.08 to 1.67; p = 0.009) and hard CVEs (HR per 10% increase: 1.46; 95% CI: 1.12 to 1.90; p = 0.006) and was strongly predictive of new-onset CHF (HR per 10% increase: 2.69; 95% CI: 1.79 to 4.04; p < 0.0001), comparing favorably to other risk factors for CHF as per various measures of model performance, reclassification, and discrimination. In a fully adjusted model, compared to nonhypertensive subjects with low RM, the HRs (95% CI) for hypertensive subjects with low RM, nonhypertensive subjects with high RM, and hypertensive subjects with high RM were 1.81 (0.85 to 3.86), 2.16 (1.07 to 5.01), and 3.98 (1.96 to 8.05), respectively. CONCLUSIONS Arterial wave reflections represent a novel strong risk factor for CHF in the general population.

CPAP, Weight Loss, or Both for Obstructive Sleep Apnea

BACKGROUND Obesity and obstructive sleep apnea tend to coexist and are associated with inflammation, insulin resistance, dyslipidemia, and high blood pressure, but their causal relation to these abnormalities is unclear. METHODS We randomly assigned 181 patients with obesity, moderate-to-severe obstructive sleep apnea, and serum levels of C-reactive protein (CRP) greater than 1.0 mg per liter to receive treatment with continuous positive airway pressure (CPAP), a weight-loss intervention, or CPAP plus a weight-loss intervention for 24 weeks. We assessed the incremental effect of the combined interventions over each one alone on the CRP level (the primary end point), insulin sensitivity, lipid levels, and blood pressure. RESULTS Among the 146 participants for whom there were follow-up data, those assigned to weight loss only and those assigned to the combined interventions had reductions in CRP levels, insulin resistance, and serum triglyceride levels. None of these changes were observed in the group receiving CPAP alone. Blood pressure was reduced in all three groups. No significant incremental effect on CRP levels was found for the combined interventions as compared with either weight loss or CPAP alone. Reductions in insulin resistance and serum triglyceride levels were greater in the combined-intervention group than in the group receiving CPAP only, but there were no significant differences in these values between the combined-intervention group and the weight-loss group. In per-protocol analyses, which included 90 participants who met prespecified criteria for adherence, the combined interventions resulted in a larger reduction in systolic blood pressure and mean arterial pressure than did either CPAP or weight loss alone. CONCLUSIONS In adults with obesity and obstructive sleep apnea, CPAP combined with a weight-loss intervention did not reduce CRP levels more than either intervention alone. In secondary analyses, weight loss provided an incremental reduction in insulin resistance and serum triglyceride levels when combined with CPAP. In addition, adherence to a regimen of weight loss and CPAP may result in incremental reductions in blood pressure as compared with either intervention alone. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT0371293 .).

Left Ventricular Mass. Allometric Scaling, Normative Values, Effect of Obesity, and Prognostic Performance

The need for left ventricular mass (LVM) normalization to body size is well recognized. Currently used allometric exponents to normalize LVM may not account for the confounding effect of sex. Because sex is a strong determinant of body size and LVM, we hypothesized that these are subject to potential bias. We analyzed data from 7528 subjects enrolled in the Asklepios Study (n=2524) and the Multiethnic Study of Atherosclerosis (limited access data set; n=5,004) to assess metric relationships between LVM and body size, generate normative data for indexed LVM, and compare the ability of normalization methods to predict cardiovascular events. The allometric exponent that adequately described the LVM-body height relationship was 1.7 in both studies and significantly different from both the unity and 2.7, whereas the LVM-body surface area relationship was approximately linear. LVM/height2.7 consistently demonstrated important residual relationships with body height and systematically misclassified subjects regarding the presence of LVH. LVH defined by LVM/height1.7 was more sensitive than LVM/body surface area to identify obesity-related LVH and was most consistently associated with cardiovascular events and all-cause death. In contrast to current assumptions, LVM/height2.7 is not an adequate method to normalize LVM for body size. We provide more appropriate normalization methods, normative data by 2D echocardiography and gradient-echo cardiac MRI, and cutoffs for defining LVH, along with prognostic validation data.

Effect of Inorganic Nitrate on Exercise Capacity in Heart Failure With Preserved Ejection Fraction

Background— Inorganic nitrate (NO3−), abundant in certain vegetables, is converted to nitrite by bacteria in the oral cavity. Nitrite can be converted to nitric oxide in the setting of hypoxia. We tested the hypothesis that NO3− supplementation improves exercise capacity in heart failure with preserved ejection fraction via specific adaptations to exercise. Methods and Results— Seventeen subjects participated in this randomized, double-blind, crossover study comparing a single dose of NO3-rich beetroot juice (NO3−, 12.9 mmol) with an identical nitrate-depleted placebo. Subjects performed supine-cycle maximal-effort cardiopulmonary exercise tests, with measurements of cardiac output and skeletal muscle oxygenation. We also assessed skeletal muscle oxidative function. Study end points included exercise efficiency (total work/total oxygen consumed), peak O2, total work performed, vasodilatory reserve, forearm mitochondrial oxidative function, and augmentation index (a marker of arterial wave reflections, measured via radial arterial tonometry). Supplementation increased plasma nitric oxide metabolites (median, 326 versus 10 &mgr;mol/L; P=0.0003), peak O2 (12.6±3.7 versus 11.6±3.1 mL O2·min−1·kg−1; P=0.005), and total work performed (55.6±35.3 versus 49.2±28.9 kJ; P=0.04). However, efficiency was unchanged. NO3− led to greater reductions in systemic vascular resistance (−42.4±16.6% versus −31.8±20.3%; P=0.03) and increases in cardiac output (121.2±59.9% versus 88.7±53.3%; P=0.006) with exercise. NO3− reduced aortic augmentation index (132.2±16.7% versus 141.4±21.9%; P=0.03) and tended to improve mitochondrial oxidative function. Conclusions— NO3− increased exercise capacity in heart failure with preserved ejection fraction by targeting peripheral abnormalities. Efficiency did not change as a result of parallel increases in total work and O2. NO3− increased exercise vasodilatory and cardiac output reserves. NO3− also reduced arterial wave reflections, which are linked to left ventricular diastolic dysfunction and remodeling. Clinical Trial Registration— URL: www.clinicaltrials.gov. Unique identifier: NCT01919177.

Cardiac Complications in Patients With Community-Acquired Pneumonia Incidence, Timing, Risk Factors, and Association With Short-Term Mortality

Background— Community-acquired pneumonia (CAP) affects >5 million adults each year in the United States. Although incident cardiac complications occur in patients with community-acquired pneumonia, their incidence, timing, risk factors, and associations with short-term mortality are not well understood. Methods and Results— A total of 1343 inpatients and 944 outpatients with community-acquired pneumonia were followed up prospectively for 30 days after presentation. Incident cardiac complications (new or worsening heart failure, new or worsening arrhythmias, or myocardial infarction) were diagnosed in 358 inpatients (26.7%) and 20 outpatients (2.1%). Although most events (89.1% in inpatients, 75% in outpatients) were diagnosed within the first week, more than half of them were recognized in the first 24 hours. Factors associated with their diagnosis included older age (odds ratio [OR]=1.03; 95% confidence interval [CI], 1.02–1.04), nursing home residence (OR, 1.8; 95% CI, 1.2–2.9), history of heart failure (OR, 4.3; 95% CI, 3.0–6.3), prior cardiac arrhythmias (OR, 1.8; 95% CI, 1.2–2.7), previously diagnosed coronary artery disease (OR, 1.5; 95% CI, 1.04–2.0), arterial hypertension (OR, 1.5; 95% CI, 1.1–2.1), respiratory rate ≥30 breaths per minute (OR, 1.6; 95% CI, 1.1–2.3), blood pH <7.35 (OR, 3.2; 95% CI, 1.8–5.7), blood urea nitrogen ≥30 mg/dL (OR, 1.5; 95% CI, 1.1–2.2), serum sodium <130 mmol/L (OR, 1.8; 95% CI, 1.02–3.1), hematocrit <30% (OR, 2.0; 95% CI, 1.3–3.2), pleural effusion on presenting chest x-ray (OR, 1.6; 95% CI, 1.1–2.4), and inpatient care (OR, 4.8; 95% CI, 2.8–8.3). Incident cardiac complications were associated with increased risk of death at 30 days after adjustment for baseline Pneumonia Severity Index score (OR, 1.6; 95% CI, 1.04–2.5). Conclusions— Incident cardiac complications are common in patients with community-acquired pneumonia and are associated with increased short-term mortality. Older age, nursing home residence, preexisting cardiovascular disease, and pneumonia severity are associated with their occurrence. Further studies are required to test risk stratification and prevention and treatment strategies for cardiac complications in this population. # Clinical Perspective {#article-title-35}Background— Community-acquired pneumonia (CAP) affects >5 million adults each year in the United States. Although incident cardiac complications occur in patients with community-acquired pneumonia, their incidence, timing, risk factors, and associations with short-term mortality are not well understood. Methods and Results— A total of 1343 inpatients and 944 outpatients with community-acquired pneumonia were followed up prospectively for 30 days after presentation. Incident cardiac complications (new or worsening heart failure, new or worsening arrhythmias, or myocardial infarction) were diagnosed in 358 inpatients (26.7%) and 20 outpatients (2.1%). Although most events (89.1% in inpatients, 75% in outpatients) were diagnosed within the first week, more than half of them were recognized in the first 24 hours. Factors associated with their diagnosis included older age (odds ratio [OR]=1.03; 95% confidence interval [CI], 1.02–1.04), nursing home residence (OR, 1.8; 95% CI, 1.2–2.9), history of heart failure (OR, 4.3; 95% CI, 3.0–6.3), prior cardiac arrhythmias (OR, 1.8; 95% CI, 1.2–2.7), previously diagnosed coronary artery disease (OR, 1.5; 95% CI, 1.04–2.0), arterial hypertension (OR, 1.5; 95% CI, 1.1–2.1), respiratory rate ≥30 breaths per minute (OR, 1.6; 95% CI, 1.1–2.3), blood pH <7.35 (OR, 3.2; 95% CI, 1.8–5.7), blood urea nitrogen ≥30 mg/dL (OR, 1.5; 95% CI, 1.1–2.2), serum sodium <130 mmol/L (OR, 1.8; 95% CI, 1.02–3.1), hematocrit <30% (OR, 2.0; 95% CI, 1.3–3.2), pleural effusion on presenting chest x-ray (OR, 1.6; 95% CI, 1.1–2.4), and inpatient care (OR, 4.8; 95% CI, 2.8–8.3). Incident cardiac complications were associated with increased risk of death at 30 days after adjustment for baseline Pneumonia Severity Index score (OR, 1.6; 95% CI, 1.04–2.5). Conclusions— Incident cardiac complications are common in patients with community-acquired pneumonia and are associated with increased short-term mortality. Older age, nursing home residence, preexisting cardiovascular disease, and pneumonia severity are associated with their occurrence. Further studies are required to test risk stratification and prevention and treatment strategies for cardiac complications in this population.

Postprandial hypertriglyceridemia increases circulating levels of endothelial cell microparticles.

Background—This study evaluated a possible relationship between levels of endothelial microparticles (EMPs), known to be a sensitive indicator of endothelial disturbance, and changes in postprandial lipid levels in healthy volunteers after a low- or high-fat meal. Methods and Results—Eighteen healthy subjects without known cardiovascular risk factors were evaluated. Lipid and EMP levels were measured before and 1 and 3 hours after a single low- or high-fat isocaloric meal. The low-fat meal had no significant postprandial effect on EMPs or lipids compared with fasting levels. In contrast, a single high-fat meal significantly increased EMP levels after 1 and 3 hours, from 389±54 (thousands per milliliter) when fasting to 541±139 (P=0.0002) and 677±159 (P<0.0001), respectively, and correlated with a postprandial elevation in serum triglycerides. Conclusions—A single high-fat meal led to a significant elevation of plasma EMP levels in healthy, normolipidemic subjects and correlated with a postprandial elevation of serum triglycerides. EMPs may be an indirect marker of endothelial dysfunction or injury induced by postprandial triglyceride-rich lipoproteins.

Aortic PWV in chronic kidney disease: A CRIC ancillary study

BACKGROUND Aortic pulse wave velocity (PWV) is a measure of arterial stiffness and has proved useful in predicting cardiovascular morbidity and mortality in several populations of patients, including the healthy elderly, hypertensives and those with end-stage renal disease receiving hemodialysis. Little data exist characterizing aortic stiffness in patients with chronic kidney disease (CKD) who are not receiving dialysis, and in particular the effect of reduced kidney function on aortic PWV. METHODS We performed measurements of aortic PWV in a cross-sectional cohort of participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study to determine factors which predict increased aortic PWV in CKD. RESULTS PWV measurements were obtained in 2,564 participants. The tertiles of aortic PWV (adjusted for waist circumference) were <7.7 m/s, 7.7-10.2 m/s, and >10.2 m/s with an overall mean (+/- s.d.) value of 9.48 +/- 3.03 m/s (95% confidence interval = 9.35-9.61 m/s). Multivariable regression identified significant independent positive associations of age, blood glucose concentrations, race, waist circumference, mean arterial blood pressure, gender, and presence of diabetes with aortic PWV and a significant negative association with the level of kidney function. CONCLUSIONS The large size of this unique cohort, and the targeted enrollment of CKD participants provides an ideal situation to study the role of reduced kidney function as a determinant of arterial stiffness. Arterial stiffness may be a significant component of the enhanced cardiovascular risk associated with kidney failure.