Overfeeding-induced weight gain elicits decreases in sex hormone-binding globulin in healthy males-Implications for body fat distribution.

OBJECTIVE: Obesity and upper-body fat elevates cardiometabolic risk. However, mechanisms predisposing to upper-body fat accumulation are not completely understood. In males, low testosterone (T) frequently associates with obesity, and estrogen deficiency may contribute to upper-body adiposity. This study examines the effects of overfeeding-induced weight gain on changes in gonadal hormones in healthy males and its association with regional fat depots. METHODS: Twenty-five males (age: 29.7 ± 6.9 years; BMI: 24.7 ± 3.1 kg/m2 ) were overfed for 8 weeks to gain approximately 5% body weight. Changes in total and regional fat depots were assessed using dual-energy x-ray absorptiometry and abdominal computed tomography scans. Circulating T, estrone (E1), 17-ß estradiol (E2), and sex hormone-binding globulin (SHBG) concentrations were measured at baseline and after weight gain. RESULTS: Overfeeding resulted in 3.8 (3.3, 4.9) kg weight gain with increased total body fat. Weight gain did not alter circulating T (p = 0.82), E1 (p = 0.52), or E2 (p = 0.28). However, SHBG decreased (p = 0.04) along with consequent increases in T/SHBG (p = 0.02) and E2/SHBG (p = 0.03) ratios. Importantly, baseline E2/SHBG ratio was inversely associated with increases in upper-body fat mass (ρ = -0.43, p = 0.03). CONCLUSIONS: Modest weight gain does not alter circulating gonadal hormones in males but may increase bioavailability of T and E2 via decreases in SHBG. The association between baseline E2/SHBG and regional fat mass suggests that higher levels of bioavailable E2 may protect from upper-body fat accumulation during overfeeding-induced modest weight gain in healthy males. Our study suggests a complex relationship between adipose tissue, gonadal hormones, and fat accumulation in males.

ECG clues for false ST-segment elevation myocardial infarction activations.

BACKGROUND: Rapid diagnosis of ST-segment elevation myocardial infarction (STEMI) is crucial for appropriate management. Catheterization for a false STEMI activation has risks including exposure to contrast agent and radiation, increased healthcare costs and delay in treatment of the primary medical condition. PATIENTS AND METHODS: This was a single center retrospective study including all 'cath alerts' between January 2012 and December 2015. 'Cath alert' is a term used to activate the interventional cardiology team when STEMI is suspected by the emergency department physicians based on review of the initial ECG. We reviewed all STEMI alerts to understand ECG differences between true and false STEMI. RESULTS: Our study population (N = 361) included 221 (61%) men and 140 (39%) women, with average age 60 ± 4.2 years. Among the 361 STEMI alerts, 82 (22.7%) did not have acute coronary syndrome. Common ECG causes of misdiagnosis included left ventricular hypertrophy (LVH, found in 40/82, 49%), early repolarization changes (20/82, 24%), right bundle branch block (RBBB) (13/82, 16%), and Brugada pattern (3/82, 4%). Multivariate regression analysis showed that LVH and RBBB were independent predictors of nonacute coronary syndrome false STEMI (odds ratio: 0.54; 95% confidence interval: 0.32-0.93; P = 0.03 for LVH, and odds ratio: 0.26, 95% confidence interval: 0.1-0.62, P = 0.004 for RBBB). CONCLUSION: The incidence of false STEMI alerts was almost 23% at our center. This number might be reduced with additional training of emergency department physicians in ECG interpretation, and recognition of common causes of misdiagnosis such as LVH, early repolarization changes, RBBB, and Brugada pattern.

Cardiac Calcifications on Echocardiography Are Associated with Mortality and Stroke.

BACKGROUND: Calcium deposits in the aortic valve and mitral annulus have been associated with cardiovascular events and mortality. However, there is no accepted standard method for scoring such cardiac calcifications, and most existing methods are simplistic. The aim of this study was to test the hypothesis that a semiquantitative score, one that accounts for all visible calcium on echocardiography, could predict all-cause mortality and stroke in a graded fashion. METHODS: This was a retrospective study of 443 unselected subjects derived from a general echocardiography database. A global cardiac calcium score (GCCS) was applied that assigned points for calcification in the aortic root and valve, mitral annulus and valve, and submitral apparatus, and points for restricted leaflet mobility. The primary outcome was all-cause mortality, and the secondary outcome was stroke. RESULTS: Over a mean 3.8 ± 1.7 years of follow-up, there were 116 deaths and 34 strokes. Crude mortality increased in a graded fashion with increasing GCCS. In unadjusted proportional hazard analysis, the GCCS was significantly associated with total mortality (hazard ratio, 1.26; 95% CI, 1.17-1.35; P < .0001) and stroke (hazard ratio, 1.23; 95% CI, 1.07-1.40; P = .003). After adjusting for demographic and clinical factors (age, gender, body mass index, diabetes, hypertension, dyslipidemia, smoking, family history of coronary disease, chronic kidney disease, history of atrial fibrillation, and history of stroke), these associations remained significant. CONCLUSIONS: The GCCS is easily applied to routinely acquired echocardiograms and has clinically significant associations with total mortality and stroke.

Relation Between Epicardial Adipose and Aortic Valve and Mitral Annular Calcium Determined by Computed Tomography in Subjects Aged ≥65 Years.

Epicardial adipose tissue (EAT) has been linked to coronary artery calcium deposits and atherosclerotic disease. Mitral annular (MAC) and aortic valve calcium (AVC) have also been associated with atherosclerosis. This study examined the possible relation between EAT thickness and valvular calcium deposits. We included 294 patients aged ≥65 years who had noncontrast computed tomography scans of the chest. Mean age was 76 ± 7 years; 47% were men. Using reconstructed images, EAT thickness was measured at various locations. MAC and AVC were quantified by Agatston technique. The sum of AVC and MAC was reported as the grand total score (GTS). Subjects were divided into 2 groups based on the value of GTS; GTS = 0, no cardiac calcification and GTS ≥1, cardiac calcification group. Epicardial fat (left and right atrioventricular grooves and superior interventricular groove) was significantly greater in the cardiac calcification group compared with the no cardiac calcification (all values, p <0.05). After adjusting for clinical variables including BMI, EAT at the superior interventricular groove remained significantly associated with total calcium. Left atrioventricular groove EAT demonstrated a trend toward an association with total calcium, but this did not reach statistical significance. In conclusion, epicardial fat is associated with calcium deposits of the mitral annulus and aortic valve.

Effect of Mitral Annular Calcium on Left Ventricular Diastolic Parameters.

Assessment of left ventricular (LV) diastolic function by Doppler flow imaging and tissue Doppler is an integral part of the echocardiographic examination. Mitral annular calcium (MAC) is frequently encountered on echocardiography. The aim of this study was to assess the impact of MAC, quantitatively measured by computed tomography scan, on echocardiographic LV diastolic parameters. We included 155 patients aged ≥65 years. Computed tomography reconstructions of the mitral annulus were created, and calcium identified and quantified by Agatston technique. Calcium locations were assigned using an overlaid template depicting the annular segments in relation to surrounding anatomic structures. Echocardiographic assessment of diastolic function was performed in standard fashion. Mean age was 77 years; 49% were men; and 43% were black. Patients with MAC had lower septal e' (p = 0.003), lateral e' (p = 0.04), and average e' (p = 0.01) compared with those without MAC. They also had a higher E-wave velocity (p = 0.01) and E/e' ratio (p <0.001). When evaluated by severity of MAC, and after adjustment for multiple clinical factors, there was a graded (inverse) relation between MAC severity and septal e' (p = 0.01), lateral e' (p = 0.01), and average e' (p = 0.01). In conclusion, LV diastolic parameters, as measured by Doppler echocardiography, are altered in the presence of MAC. This could be due to direct effects of MAC on annular function or might reflect truly reduced diastolic function. Interpretation of diastolic parameters in patients with MAC should be performed with caution.

Distribution of Mitral Annular and Aortic Valve Calcium as Assessed by Unenhanced Multidetector Computed Tomography.

Aging is associated with calcium deposits in various cardiovascular structures, but patterns of calcium deposition, if any, are unknown. In search of such patterns, we performed quantitative assessment of mitral annular calcium (MAC) and aortic valve calcium (AVC) in a broad clinical sample. Templates were created from gated computed tomography (CT) scans depicting the aortic valve cusps and mitral annular segments in relation to surrounding structures. These were then applied to CT reconstructions from ungated, clinically indicated CT scans of 318 subjects, aged ≥65 years. Calcium location was assigned using the templates and quantified by the Agatston method. Mean age was 76 ± 7.3 years; 48% were men and 58% were white. Whites had higher prevalence (p = 0.03) and density of AVC than blacks (p = 0.02), and a trend toward increased MAC (p = 0.06). Prevalence of AVC was similar between men and women, but AVC scores were higher in men (p = 0.008); this difference was entirely accounted for by whites. Within the aortic valve, the left cusp was more frequently calcified than the others. MAC was most common in the posterior mitral annulus, especially its middle (P2) segment. For the anterior mitral annulus, the medial (A3) segment calcified most often. In conclusion, AVC is more common in whites than blacks, and more intense in men, but only in whites. Furthermore, calcium deposits in the mitral annulus and aortic valve favor certain locations.

Echocardiographic strain and mortality in Black Americans with end-stage renal disease on hemodialysis.

End-stage renal disease (ESRD) presents a significant health burden and is associated with high cardiovascular morbidity and mortality. This is particularly true in African Americans who generally have higher rates of cardiovascular mortality. Outcomes in ESRD are related to extent of cardiovascular disease, but markers for outcome are not clearly established. Global longitudinal strain (GLS) has emerged as an important measure of left ventricular systolic function that is additive to traditional ejection fraction (EF). It can be measured on routine digital echocardiography and is reproducible. This study tested the hypothesis that GLS is associated with mortality in black Americans with ESRD and preserved EF. Forty-eight outpatients undergoing hemodialysis, 59.4 ± 13.3 years, with EF ≥50% were prospectively enrolled. GLS, measured by an offline speckle tracking algorithm, ranged from -8.6% to -22.0% with a mean of -13.4%, substantially below normal (-16% or more negative). The prevalence of left ventricular systolic dysfunction, as determined by GLS, was 89%. Patients were followed for an average of 1.9 years; all-cause mortality was 19% (9 deaths). GLS was significantly associated with mortality (hazard ratio 1.15, 95% confidence interval 1.02 to 1.30, p = 0.02), whereas EF was not. After adjustment for multiple potential confounders (age, gender, race, smoking, hypertension, diabetes, hyperlipidemia, coronary disease, heart failure, and EF), GLS remained strongly associated with mortality (hazard ratio 1.30, 95% confidence interval 1.10 to 1.56, p = 0.002). In conclusion, GLS is an important index in patients with ESRD, which is additive to EF as a marker for mortality in this high-risk group.

Calcification of the mitral valve and annulus: systematic evaluation of effects on valve anatomy and function.

BACKGROUND: Mitral annular calcification (MAC) is common in chronic kidney disease. It is associated with cardiovascular events and can cause valvular dysfunction, but it has not been systematically characterized. The aim of this prospective study was to assess the prevalence and distribution of MAC, its effects on leaflet motion, and its association with mitral stenosis and mitral regurgitation (MR) in a hemodialysis population. METHODS: Echocardiograms were obtained in 75 consecutive hemodialysis outpatients. MAC extent and distribution were graded semiquantitatively using two-dimensional and three-dimensional echocardiography. Associations with the presence and severity of mitral stenosis and MR were explored. RESULTS: The mean age was 60 ± 14 years; 60% were men, and 87% were African American. MAC was present in 64% (moderate to severe in 48%). Calcium extended more than halfway onto the leaflet in 37% and beyond the annulus in 40%. Leaflet motion was restricted in 37%. Mitral stenosis was present in 28%, and the extent of calcification was associated with mean mitral valve gradient (P < .0001). MR was prevalent (present in 81%) but was severe in none. The severity of MAC was greater in patients with moderate MR than in those with no or mild MR (P = .04). Three-dimensional analysis suggested an uneven distribution of annular calcium; the middle and lateral anterior segments were less often calcified than the anterior-medial or posterior segments. Calcification in any annular segment was highly associated with restricted motion of the attached leaflet segment. CONCLUSIONS: MAC is common and often extensive in hemodialysis patients. Calcium may be unevenly distributed among the annular segments. When present, annular calcification reduces the angle of leaflet opening and can cause valvular dysfunction.

Prediction of significant conduction disease through noninvasive assessment of cardiac calcification.

AIMS: Cardiac calcification is associated with coronary artery disease, arrhythmias, conduction disease, and adverse cardiac events. Recently, we have described an echocardiographic-based global cardiac calcification scoring system. The objective of this study was to evaluate the severity of cardiac calcification in patients with permanent pacemakers as based on this scoring system. METHODS AND RESULTS: Patients with a pacemaker implanted within the 2-year study period with a previous echocardiogram were identified and underwent blinded global cardiac calcium scoring. These patients were compared to matched control patients without a pacemaker who also underwent calcium scoring. The study group consisted of 49 patients with pacemaker implantation who were compared to 100 matched control patients. The mean calcium score in the pacemaker group was 3.3 ± 2.9 versus 1.8 ± 2.0 (P = 0.006) in the control group. Univariate and multivariate analysis revealed glomerular filtration rate and calcium scoring to be significant predictors of the presence of a pacemaker. CONCLUSION: Echocardiographic-based calcium scoring correlates with the presence of severe conduction disease requiring a pacemaker.

Leptin signaling in adipose tissue: role in lipid accumulation and weight gain.

RATIONALE: The link between obesity, hyperleptinemia, and development of cardiovascular disease is not completely understood. Increases in leptin have been shown to impair leptin signaling via caveolin-1-dependent mechanisms. However, the role of hyperleptinemia versus impaired leptin signaling in adipose tissue is not known. OBJECTIVE: To determine the presence and significance of leptin-dependent increases in adipose tissue caveolin-1 expression in humans. METHODS AND RESULTS: We designed a longitudinal study to investigate the effects of increases in leptin on adipose tissue caveolin-1 expression during weight gain in humans. Ten volunteers underwent 8 weeks of overfeeding, during which they gained an average weight of 4.1±1.4 kg, with leptin increases from 7±3.8 to 12±5.7 ng/mL. Weight gain also resulted in changes in adipose tissue caveolin-1 expression, which correlated with increases in leptin (rho=0.79, P=0.01). In cultured human white preadipocytes, leptin increased caveolin-1 expression, which in turn impaired leptin cellular signaling. Functionally, leptin decreased lipid accumulation in differentiating human white preadipocytes, which was prevented by caveolin-1 overexpression. Further, leptin decreased perilipin and fatty acid synthase expression, which play an important role in lipid storage and biogenesis. CONCLUSIONS: In healthy humans, increases in leptin, as seen with modest weight gain, may increase caveolin-1 expression in adipose tissue. Increased caveolin-1 expression in turn impairs leptin signaling and attenuates leptin-dependent lowering of intracellular lipid accumulation. Our study suggests a leptin-dependent feedback mechanism that may be essential to facilitate adipocyte lipid storage during weight gain.

Can total cardiac calcium predict the coronary calcium score?

BACKGROUND: Mitral annular calcification (MAC) shares the same risk factors as atherosclerosis and is associated with coronary artery disease as well as cardiovascular events. However, sensitivity and positive predictive value are low. We hypothesized that a global echocardiographic calcium score would better predict coronary atherosclerotic burden, as assessed by coronary artery calcium score (CAC), than MAC alone. METHODS: An echocardiographic score was devised to measure global cardiac calcification in a semi-quantitative manner; this included calcification in the aortic valve and root, the mitral valve and annulus, and the sub-mitral apparatus. This score, and a simplified version, were compared with a similar calcification score by CT scan, as well as the CAC. RESULTS: There was a good correlation between the two global calcification scores; the echocardiographic score also correlated with CAC. Using CAC >400 as a measure of severe coronary atherosclerosis, an echocardiographic score ≥5 had a positive predictive value of 60%. Importantly, the simplified score performed equally well (≥3 had a positive predictive value of 62%). CONCLUSIONS: Global cardiac calcification, assessed by CT scan or echocardiography, correlates with the extent of coronary calcium. A semi-quantitative calcium score can be easily applied during routine echocardiographic interpretation and can alert the reader to the possibility of severe coronary atherosclerosis.

Interactions between obesity and obstructive sleep apnea: implications for treatment.

Obstructive sleep apnea (OSA) adversely affects multiple organs and systems, with particular relevance to cardiovascular disease. Several conditions associated with OSA, such as high BP, insulin resistance, systemic inflammation, visceral fat deposition, and dyslipidemia, are also present in other conditions closely related to OSA, such as obesity and reduced sleep duration. Weight loss has been accompanied by improvement in characteristics related not only to obesity but to OSA as well, suggesting that weight loss might be a cornerstone of the treatment of both conditions. This review seeks to explore recent developments in understanding the interactions between body weight and OSA. Weight loss helps reduce OSA severity and attenuates the cardiometabolic abnormalities common to both diseases. Nevertheless, weight loss has been hard to achieve and maintain using conservative strategies. Since bariatric surgery has emerged as an alternative treatment of severe or complicated obesity, impressive results have often been seen with respect to sleep apnea severity and cardiometabolic disturbances. However, OSA is a complex condition, and treatment cannot be limited to any single symptom or feature of the disease. Rather, a multidisciplinary and integrated strategy is required to achieve effective and long-lasting therapeutic success.

Concentration of apolipoprotein B is comparable with the apolipoprotein B/apolipoprotein A-I ratio and better than routine clinical lipid measurements in predicting coronary heart disease mortality: findings from a multi-ethnic US population.

AIMS: Prospective studies indicate that apolipoprotein measurements predict coronary heart disease (CHD) risk; however, evidence is conflicting, especially in the US. Our aim was to assess whether measurements of apolipoprotein B (apoB) and apolipoprotein A-I (apoA-I) can improve the ability to predict CHD death beyond what is possible based on traditional cardiovascular (CV) risk factors and clinical routine lipid measurements. METHODS AND RESULTS: We analysed prospectively associations of apolipoprotein measurements, traditional CV risk factors, and clinical routine lipid measurements with CHD mortality in a multi-ethnic representative subset of 7594 US adults (mean age 45 years; 3881 men and 3713 women, median follow-up 124 person-months) from the Third National Health and Nutrition Examination Survey mortality study. Multiple Cox-proportional hazards regression was applied. There were 673 CV deaths of which 432 were from CHD. Concentrations of apoB [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.09-3.61], apoA-I (HR 0.48, 95% CI 0.27-0.85) and total cholesterol (TC) (HR 1.17, 95% CI 1.02-1.34) were significantly related to CHD death, whereas high density lipoprotein cholesterol (HDL-C) (HR 0.68, 95% CI 0.45-1.05) was borderline significant. Both the apoB/apoA-I ratio (HR 2.14, 95% CI 1.11-4.10) and the TC/HDL-C ratio (HR 1.10, 95% CI 1.04-1.16) were related to CHD death. Only apoB (HR 2.01, 95% CI 1.05-3.86) and the apoB/apoA-I ratio (HR 2.09, 95% CI 1.04-4.19) remained significantly associated with CHD death after adjusting for CV risk factors. CONCLUSION: In the US population, apolipoprotein measurements significantly predict CHD death, independently of conventional lipids and other CV risk factors (smoking, dyslipidaemia, hypertension, obesity, diabetes and C-reactive protein). Furthermore, the predictive ability of apoB alone to detect CHD death was better than any of the routine clinical lipid measurements. Inclusion of apolipoprotein measurements in future clinical guidelines should not be discarded.

Cardiovascular risk after bariatric surgery for obesity.

Obese patients have an increased prevalence of cardiovascular (CV) risk factors, which improve with bariatric surgery, but whether bariatric surgery reduces long-term CV events remains ill defined. A systematic review of published research was conducted, and CV risk models were applied in a validation cohort previously published. A standardized MEDLINE search using terms associated with obesity, bariatric surgery, and CV risk factors identified 6 test studies. The validation cohort consisted of a population-based, historical cohort of 197 patients who underwent Roux-en-Y gastric bypass and 163 control patients, identified through the Rochester Epidemiology Project. Framingham and Prospective Cardiovascular Munster Heart Study (PROCAM) risk scores were applied to calculate 10-year CV risk. In the validation cohort, absolute 10-year Framingham risk score for CV events was lower at follow-up in the bariatric surgery group (7.0% to 3.5%, p <0.001) compared with controls (7.1% to 6.5%, p = 0.13), with an intergroup absolute difference in risk reduction of 3% (p <0.001). PROCAM risk in the bariatric surgery group decreased from 4.1% to 2.0% (p <0.001), whereas the control group exhibited only a modest decrease (4.4% to 3.8%, p = 0.08). Using mean data from the validation study, the trend and directionality in risk was similar in the Roux-en-Y group. The test studies confirmed the directionality of CV risk, with estimated relative risk reductions for bariatric surgery patients ranging from 18% to 79% using the Framingham risk score compared with 8% to 62% using the PROCAM risk score. In conclusion, bariatric surgery predicts long-term decreases in CV risk in obese patients.

Effect of bariatric surgery on the metabolic syndrome: a population-based, long-term controlled study.

OBJECTIVE: To assess the effect of weight loss by bariatric surgery on the prevalence of the metabolic syndrome (MetS) and to examine predictors of MetS resolution. PATIENTS AND METHODS: We performed a population-based, retrospective study of patients evaluated for bariatric surgery between January 1, 1990, and December 31, 2003, who had MetS as defined by the American Heart Association/National Heart, Lung, and Blood Institute (increased triglycerides, low high-density lipoprotein, increased blood pressure, increased fasting glucose, and a measure of obesity). Of these patients, 180 underwent Roux-en-Y gastric bypass, and 157 were assessed in a weight-reduction program but did not undergo surgery. We determined the change in MetS prevalence and used logistic regression models to determine predictors of MetS resolution. Mean follow-up was 3.4 years. RESULTS: In the surgical group, all MetS components improved, and medication use decreased. Nonsurgical patients showed improvements in high-density lipoprotein cholesterol levels. After bariatric surgery, the number of patients with MetS decreased from 156 (87%) of 180 patients to 53 (29%); of the 157 nonsurgical patients, MetS prevalence decreased from 133 patients (85%) to 117 (75%). A relative risk reduction of 0.59 (95% confidence interval [CI], 0.48-0.67; P<.001) was observed in patients who underwent bariatric surgery and had MetS at follow-up. The number needed to treat with surgery to resolve 1 case of MetS was 2.1. Results were similar after excluding patients with diabetes or cardiovascular disease or after using diagnostic criteria other than body mass index for MetS. Significant predictors of MetS resolution included a 5% loss in excess weight (odds ratio, 1.26; 95% CI, 1.19-1.34; P<.001) and diabetes mellitus (odds ratio, 0.32; 95% CI, 0.15-0.68; P=.003). CONCLUSION: Roux-en-Y gastric bypass induces considerable and persistent improvement in MetS prevalence. Our results suggest that reversibility of MetS depends more on the amount of excess weight lost than on other parameters.

Prognostic importance of weight loss in patients with coronary heart disease regardless of initial body mass index.

BACKGROUND: Recently, mild elevations in body mass index (BMI) have been related to better outcomes in patients with coronary heart disease. Our aim was to determine whether patients with coronary heart disease who are participating in cardiac rehabilitation would have improved outcomes if they lost weight and whether this would depend on initial BMI. METHODS: This is a prospective cohort study of 377 consecutive patients enrolled at a cardiac rehabilitation program, aged 30-85 years with a mean follow-up of 6.4+/-1.8 years. We measured total mortality, acute cardiovascular events (fatal and nonfatal myocardial infarction, fatal and nonfatal stroke, emergent revascularization in the setting of unstable angina, and hospitalization for congestive heart failure) and a composite outcome (mortality+acute cardiovascular events). Statistical testing used Cox Proportional Hazards Regression. RESULTS: On average, the weight loss group (n=220) lost 3.6+/-4.1 kg, and the nonweight loss group (n=157) gained 1.5+/-1.4 kg (P<0.0001). The rate of the composite outcome was 24% (53/220) in those who did lose weight versus 37% (58/157) in those who did not lose weight. Weight loss was significantly associated with lower rate of the composite outcome after adjustment for age, sex, smoking, dyslipidemia, diabetes, hypertension, myocardial infarction, and obese status [hazard ratio (HR)=0.62; P=0.018]. Subgroup analysis showed that patients who lost weight had favorable outcomes both in patients with BMI<25 (HR=0.32; P=0.035) and those with BMI>or=25 kg/m (HR=0.64; P=0.032). CONCLUSIONS: Weight loss in cardiac rehabilitation is a marker for favorable long-term outcomes, regardless of initial BMI.

Relationships between leptin and C-reactive protein with cardiovascular disease in the adult general population.

BACKGROUND: Leptin could be a key regulator of C-reactive protein (CRP) levels, which serve as a marker of systemic inflammation. Both leptin and CRP are predictors of cardiovascular disease (CVD). However, the interactions between leptin and CRP, and their association with CVD, remain unclear. We therefore studied them in a large, multiethnic population. METHODS: We analyzed leptin and CRP levels, anthropometric variables and cardiovascular risk factor data from 6,251 participants from the Third National Health and Nutrition Examination Survey (NHANES III). Logistic regression was used to estimate the association between leptin, CRP and CVD (defined as history of myocardial infarction or stroke). Receiver operating characteristic curves were created to study the additional value of leptin and CRP for the association with CVD. RESULTS: The mean age was 44.4 +/- 0.21 years (52.5% women). After adjustment for age, race, dyslipidemia, hypertension, diabetes, smoking, obesity and CRP, high levels of leptin were significantly associated with CVD in men (odds ratio 2.47, 95% CI 1.19-5.19) and in women (odds ratio 3.30, 95% CI 1.47-7.99). After adjustment for leptin, CRP was not associated with CVD. There was a significant correlation between levels of leptin and CRP (Spearman correlation rho = 0.22 in men and rho = 0.32 in women, both P < 0.0001). The area under the curve, representing the association between cardiovascular risk factors and CVD, increased after the addition of high levels of both leptin and CRP together. CONCLUSION: High leptin levels are independently associated with CVD even after adjustment for CRP; elevated CRP levels are not associated with CVD after adjustment for leptin. However, increased concentrations of both leptin and CRP confer the highest risk for CVD.

Doppler strain imaging closely reflects myocardial energetic status in acute progressive ischemia and indicates energetic recovery after reperfusion.

BACKGROUND: Capitalizing on mechanoenergetic coupling, we investigated whether strain echocardiography can noninvasively estimate the ratio of adenosine triphosphate (ATP) to adenosine diphosphate (ADP), a marker of energetic status during acute myocardial ischemia and reperfusion. METHODS: Twenty-eight pigs were divided into 7 groups (1 baseline, 4 ischemic, and 2 reperfusion). Ischemia was induced by left anterior descending coronary artery occlusion. Longitudinal systolic lengthening (SL) and postsystolic shortening (PSS) strain were measured by echocardiography. The ATP/ADP ratio was obtained from myocardial biopsies in the ischemic and control regions. RESULTS: SL and PSS strain and the ATP/ADP ratio progressively decreased (P < .05) with increased duration (12, 40, 120, and 200 minutes) of ischemia. A mathematical formula (ATP/ADP = -0.97 + 0.25 x PSS strain + 0.20 x SL strain) estimated best the ATP/ADP ratio (r = 0.94, P < .05). Reperfusion after 12 but not after 120 minutes of ischemia significantly improved the ATP/ADP ratio and decreased SL and PSS strain. CONCLUSIONS: Strain echocardiography closely reflected changes and enabled the noninvasive estimation of the ATP/ADP ratio. A higher ATP/ADP ratio is associated with functional improvement after reperfusion.

Relation of increased leptin concentrations to history of myocardial infarction and stroke in the United States population.

Leptin, an adipose tissue-derived hormone, has been linked to cardiovascular outcomes; however, data are limited in the United States population, especially women. To assess the association between leptin concentrations and history of myocardial infarction (MI) and stroke independently of traditional cardiovascular risk factors, we analyzed data from 6,239 subjects (mean age 47 years; 3,336 women) with measurements of serum leptin and full assessment of cardiovascular risk factors from the National Health and Nutrition Examination Survey (NHANES) III. Logistic regression was used to estimate the cross-sectional association of leptin concentrations (highest quartile versus lowest quartile) and history of MI, stroke, and the composite end point of MI or stroke (MI/stroke). Gender-specific models of leptin were adjusted for age, race, dyslipidemia, hypertension, diabetes, smoking, and obesity status. There were 212 men with MI/stroke (5.4%), 154 with MI (4.1%), and 82 with stroke (1.7%). There were 135 women with MI/stroke (2.6%), 74 with MI (1.5%), and 78 with stroke (1.4%). In multivariate analysis, high leptin level was significantly and independently associated with MI/stroke in men (odds ratio [OR] 2.41, 95% confidence interval [CI] 1.20 to 4.93) and women (OR 4.26, 95% CI 1.75 to 10.73); with MI in men (OR 3.16, 95% CI 1.40 to 7.37) and women (OR 3.96, 95% CI 1.29 to 12.72), and with stroke in women (OR 3.20, 95% CI 1.04 to 10.54) but not in men (OR 1.37, 95% CI 0.38 to 3.88). In conclusion, in the United States population, increased leptin concentrations are significantly associated with MI/stroke in men and women independently of traditional cardiovascular risk factors and obesity status.