Dyslipidemia in the metabolic syndrome: clinical implications and management.

Dyslipidemia is an important component of the metabolic syndrome. Dyslipidemia in the metabolic syndrome is characterized by hypertriglyceridemia, low serum levels of high density lipoprotein cholesterol (HDL-C) and an increase in the serum fraction of small dense low density lipoprotein cholesterol (LDL-C) particles. Serum LDL-C elevation is frequently present, but is not a criterion of the metabolic syndrome. A Medline search was conducted using the terms metabolic syndrome, dyslipidemia, hypertriglyceridemia and HDL cholesterol. The metabolic syndrome is a common and important risk factor for cardiovascular disease and progression to type 2 diabetes mellitus. Dyslipidemia is present in most patients with the metabolic syndrome and is treatable with therapeutic lifestyle changes and pharmacotherapy. Aggressive management of atherogenic dyslipidemia is justified by the very high cardiovascular risk associated with this disorder. Atherogenic dyslipidemia is frequently present in patients with the metabolic syndrome and requires aggressive treatment due to the very high risk for cardiovascular disease and progression to type 2 diabetes mellitus.

Effect of obesity and weight loss on ventricular repolarization: a systematic review and meta-analysis.

We performed a systematic review and meta-analysis of the effects of obesity ± overweight and weight loss on the corrected QT interval (QTc) and QT or QTc dispersion (indices of ventricular repolarization). Mean difference for both QTc and QT or QTc dispersion with 95% confidence intervals (CIs) was calculated comparing obese ± overweight subjects and normal weight controls and QTc and QT or QTc dispersion before and after weight loss from diet ± exercise or bariatric surgery. A total of 22 studies fulfilled the selection criteria. Compared with normal weight controls, there was a significantly longer QTc in obese ± overweight subjects (mean difference of 21.74 msec, 95% CI: 18.76 to 22.32) and significantly longer QT or QTc dispersion (mean difference of 15.17 msec, 95% CI: 13.59 to 16.74). Weight loss was associated with a significant decrease in QTc (mean difference -25.77 msec, 95% CI: -28.33-23.21) and QT or QTc dispersion (mean difference of -13.46 msec, 95% CI: -15.60 to -11.32 in obese ± overweight subjects. Thus, obesity ± overweight is associated with significant prolongation of QTc and QT or QTC dispersion. Weight loss in obese ± overweight subjects produces significant decreases in these variables. © 2016 World Obesity.

Obesity and the electrocardiogram.

Obesity is associated with a wide variety of electrocardiographic (ECG) abnormalities. Most of these reflect alterations in cardiac morphology. Some serve as markers of risk for sudden death. Key ECG abnormalities or alterations occurring with disproportionately high frequency in obese subjects include: leftward shifts of the P wave QRS and T wave axes, various changes in P wave morphology, low QRS voltage, various markers of left ventricular hypertrophy (particularly the Cornell voltage and product), T wave flattening in the inferior and lateral leads, lengthening of the corrected QT interval and prolonged QT interval duration. Alterations in the signal-averaged ECG and in heart rate variability may be arrhythmogenic. Cardiac arrhythmias have been described in obese subjects, but are often accompanied by left ventricular hypertrophy or the sleep apnea syndrome. Many of these ECG abnormalities are reversible with substantial weight loss. Thus, obesity is associated with a wide variety of ECG abnormalities, many of which are corrected by weight loss.

Comparative survival after permanent ventricular and dual chamber pacing for patients with chronic high degree atrioventricular block with and without preexistent congestive heart failure.

To determine whether survival after permanent ventricular demand (VVI) pacing differs from survival after permanent dual chamber (DVI or DDD) pacing in patients with chronic high degree atrioventricular (AV) block (Mobitz type II or trifascicular block), 132 patients who received a VVI pacemaker (Group 1) and 48 patients who received a DVI or DDD pacemaker (Group 2) were followed up for 1 to 5 years. There was no significant difference in sex distribution, mean age or incidence of coronary heart disease, hypertension, valvular heart disease, diabetes mellitus, stroke or renal failure between Groups 1 and 2. Overall, the predicted cumulative survival rate at 1, 3 and 5 years was 89, 76 and 73%, respectively, for Group 1 and 95, 82 and 70%, respectively, for Group 2. In patients with preexistent congestive heart failure, the predicted cumulative survival rate at 1, 3 and 5 years was 85, 66 and 47%, respectively, for Group 1 (n = 53) and 94, 81 and 69%, respectively, for Group 2 (n = 20). The 5 year predicted cumulative survival rate was significantly lower in Group 1 patients with preexistent congestive heart failure than in Group 2 patients with the same condition (p less than 0.02). There was no significant difference in 5 year cumulative survival rate between Groups 1 and 2 for patients without preexistent congestive heart failure. The results suggest that permanent dual chamber pacing enhances survival to a greater extent than does permanent ventricular demand pacing in patients with high degree AV block and preexistent congestive heart failure.

Electrocardiographic diagnosis of left atrial enlargement.

Established scalar electrocardiographic criteria for left atrial enlargement are based on abnormalities of the P-terminal force, total P-wave duration, and the relationship of total P-wave duration to PR-interval duration. These electrocardiographic signs may also result from left atrial hypertension, left atrial hypertrophy, and interatrial conduction defects. This article describes the scalar electrocardiographic criteria for left atrial enlargement in current use, and provides a critical appraisal of their efficacy in diagnosis.

Rapid control of severe hypertension with minoxidil.

We studied nine symptomatic patients whose diastolic BP exceeded 120 mm Hg two hours after receiving a combination of 40 mg of oral propranolol hydrochloride and 40 mg of oral furosemide. Systemic and pulmonary hemodynamics were measured before and after a 20-mg loading dose of oral minoxidil. A booster dosage of 5 to 20 mg of minoxidil was given at four hours if the diastolic BP exceeded 100 mm Hg. There was a progressive and significant reduction of systemic vascular resistance and systolic diastolic BP during the period of hemodynamic monitoring. The decrease in systemic vascular resistance occurred without notable change in cardiac output or pulmonary wedge pressure. The results indicate that an orally administered regimen of propranolol, furosemide, and loading-booster doses of minoxidil produces prompt, progressive, and sustained BP reduction due to vasodilation in patients with severe hypertension who require prompt (but not immediate) BP control.

Effect of beta-blockade on right ventricular performance in patients with and without right ventricular dysfunction due to coronary artery disease.

To assess the effects of beta-blockade on right ventricular performance in patients with and without right ventricular dysfunction due to coronary artery disease, we performed radionuclide ventriculography on eight patients with normal right ventricular ejection fraction (RVEF greater than or equal to 35%) and 14 patients with mild to moderate right ventricular dysfunction (RVEF less than 35%) at rest. All patients had chronic stable angina pectoris, and nine patients had prior myocardial infarction. Radionuclide ventriculography was performed on placebo and during clinical beta-blockade (heart rate, 50 to 60 beats per minute and less than or equal to 20% increase in heart rate over baseline during stage I treadmill exercise, Bruce protocol) with the oral, cardioselective beta-blocking agent, betaxolol. The resting RVEF (mean +/- 1 SD) was 33% +/- 7% on placebo and 34% +/- 7% during clinical beta-blockade. Mean exercise RVEF was 40% +/- 8% on placebo and 39% +/- 8% during clinical beta-blockade. These differences were not statistically significant. Resting left ventricular ejection fraction ranged from 22% to 60% (mean, 42% +/- 8%). On placebo, one of eight patients with a resting RVEF greater than or equal to 35% had a normal exercise RVEF response (greater than or equal to 5% increment) whereas nine of 14 patients with resting RVEF less than 35% had normal exercise response. The discordant relationship between baseline RVEF and exercise response on placebo became less marked during clinical beta-blockade. We conclude that beta-blockade does not produce significant deterioration of right ventricular systolic function or right ventricular reserve either in patients with normal or in those with mild to moderately impaired resting right ventricular systolic function.

Sensitivity and specificity of electrocardiographic criteria for left and right ventricular hypertrophy in morbid obesity.

To determine the sensitivity and specificity of standard electrocardiographic criteria for left ventricular (LV) and right ventricular (RV) hypertrophy in morbid obesity, resting electrocardiograms and M-mode echocardiograms were obtained in 65 patients whose actual body weight was more than twice their ideal body weight and who were free from hypertension and organic heart disease not directly attributable to obesity. Electrocardiographic criteria for LV hypertrophy were tested using increased LV wall thickness, LV enlargement and increased LV mass (all determined echocardiographically) as diagnostic standards. Electrocardiographic criteria for RV hypertrophy were tested using echocardiographic RV enlargement or RV hypertrophy as a diagnostic standard. Sensitivity values for the electrocardiographic criteria for LV hypertrophy ranged from 0 to 13%, 0 to 20% and 0 to 12% using echocardiographic increased LV wall thickness, LV enlargement and increased LV mass, respectively, as diagnostic standards. Specificity values ranged from 73 to 100%, 87 to 100% and 83 to 100%, respectively, using these diagnostic standards. Sensitivity values for the electrocardiographic criteria for RV hypertrophy ranged from 0 to 16% and specificity values ranged from 95 to 100%. Combining electrocardiographic criteria within groups did not appreciably increase sensitivity and often decreased specificity to unacceptably low levels. The electrocardiogram is very limited in its ability to detect ventricular hypertrophy and chamber enlargement in morbidly obese patients.

Effect of weight loss on cardiac chamber size, wall thickness and left ventricular function in morbid obesity.

To determine cardiac chamber size, wall thickness and left ventricular (LV) systolic function in morbidly obese patients, M-mode and cross-sectional echocardiography was performed in 62 patients whose body weight was greater than or equal to twice their ideal weight but who were free from underlying organic heart disease and systemic hypertension. The initial clinical protocol consisted of a medical history, physical examination, electrocardiogram at rest, chest x-ray and echocardiogram. Thereafter, each patient underwent gastric restriction. Thirty-four patients returned for follow-up echocardiography 4.3 +/- 0.3 months after substantial weight loss was achieved. For the whole group (n = 62) and LV internal dimension in diastole was enlarged in 24 (39%), the right ventricular internal dimension was enlarged in 20 (32%), the left atrial dimension was enlarged in 25 (40%) and the ventricular septal and LV posterior wall thickness was increased in 35 (56%). In the 34 patients who returned for follow-up, mean body weight decreased significantly, from 135 +/- 8 to 79 +/- 6 kg (73 +/- 4% of the amount over ideal body weight). In the subgroup with low preoperative LV fractional shortening (n = 13), mean LV fractional shortening increased from 22 +/- 2% to 31 +/- 2% (p less than 0.01). This was accompanied by a significant decrease in the mean LV internal dimension in diastole and mean blood pressure. The results indicate that cardiac chamber enlargement, LV hypertrophy and LV systolic dysfunction occur frequently in morbidly obese patients and that LV systolic dysfunction in such persons may improve following substantial weight loss.

Effect of exercise on left ventricular systolic function and reserve in morbid obesity.

To assess the effect of exercise on left ventricular (LV) systolic function and reserve in morbid obesity, radionuclide left ventriculography was performed before and during supine, symptom-limited bicycle exercise in 23 patients whose body weight was greater than or equal to twice their ideal body weight. Echocardiography was performed before exercise. Resting LV ejection fraction was depressed in 13 patients and LV mass was increased in 10 patients. Exercise produced nonsignificant increases (of similar magnitude) in mean LV ejection fraction in the subgroups with normal and depressed resting LV ejection fraction. Exercise produced a significant increase in LV ejection fraction from 54 +/- 8 to 65 +/- 12% (p less than 0.005) in the subgroup with normal LV mass, but produced no significant change in LV ejection fraction in the subgroup with increased LV mass (53 +/- 10 at rest, 50 +/- 12% during exercise). Moreover, the LV exercise response (change in LV ejection fraction during exercise) in the subgroup with normal LV mass was significantly different from that in the subgroup with increased LV mass (p less than 0.005). There was a strong positive correlation between LV mass and the percent over ideal body weight (r = 0.912, p = 0.01) and a strong negative correlation between LV mass and LV exercise response (r = 0.829, p = 0.01). The results suggest that increased LV mass predisposes morbidly obese patients to impairment of LV systolic function during exercise.

Prevalence of intraatrial thrombus in patients with atrial flutter.

In summary, left atrial thrombus occurs with disproportionately high frequency in patients hospitalized with atrial flutter. Male gender and a left ventricular ejection fraction < 40% are predictors of left atrial thrombus formation in such patients.

Sensitivity and specificity of commonly used electrocardiographic criteria for left atrial enlargement determined by M-mode echocardiography.

To assess the sensitivity and specificity of 6 commonly used electrocardiographic criteria for left atrial (LA) enlargement, the rest ECGs of 99 patients in normal sinus rhythm were analyzed. Fifty-seven of the patients had LA enlargement and 42 had a normal LA dimension as determined by M-mode echocardiography. The 6 criteria studied and their respective sensitivities and specificities were as follows: (1) duration of the negative phase of the P wave in lead V1 greater than 40 ms: sensitivity, 83%; specificity, 80%; (2) notched P wave in any standard lead with an interpeak duration greater than 40 ms: sensitivity, 15%; specificity, 100%; (3) P terminal force (depth X duration of the terminal portion of the P wave) in lead V1 more negative than -0.04 mm X s: sensitivity, 69%; specificity 93%; (4) depth of the negative phase of the P wave in lead V1 greater than or equal to 1 mm: sensitivity, 60%; specificity, 93%; (5) total P-wave duration greater than 110 ms in any standard lead: sensitivity, 33%; specificity, 88%; (6) total P wave duration/P-R interval duration greater than 1.6: sensitivity, 31%; specificity, 64%. Combining 2 or more of these criteria did not substantially improve sensitivity and specificity.

Factors predicting coronary artery disease in patients with giant negative T waves.

Seventy-four patients with giant negative T waves were studied to determine which electrocardiographic variables predicted the presence of coronary artery disease. The absence of left ventricular hypertrophy and the presence of symmetric T-wave inversion predicted coronary artery disease.

Left ventricular mass and systolic function in human immunodeficiency virus-infected patients after weight loss.

Transthoracic echocardiography was performed on 27 patients with human immunodificiency virus after weight loss and in 20 lean controls. Left ventricular mass index was significantly higher and left ventricular fractional shortening was significantly lower in patients with human immunodificiency virus after weight loss than in lean, normal controls.

Sensitivity and specificity of M mode echocardiographic signs of mitral valve prolapse.

To assess the sensitivity and specificity of previously described M mode echocardiographic signs of mitral valve prolapse, 100 subjects with a mobile mid systolic click and 100 matched normal control subjects were prospectively studied. Late systolic posterior motion and holosystolic hammocking of the mitral leaflets were common, highly specific signs of mitral valve prolapse. When these signs were combined as a single criterion, sensitivity was 85 percent and specificity was 99 percent. Other signs, including systolic echoes in the mid left atrium, systolic anterior motion, early diastolic anterior motion of the posterior mitral leaflet and shaggy or heavy cascading linear diastolic echoes posterior to the mitral valve, were highly specific but uncommon. They occurred only in combination with late systolic posterior motion or holosystolic hammocking. The remaining signs tested did not differentiate subjects with mitral valve prolapse from normal persons.

Factors influencing left ventricular systolic function in nonhypertensive morbidly obese patients, and effect of weight loss induced by gastroplasty.

Heart rate and blood pressure were measured, and echocardiography was performed in 39 patients whose actual body weight was greater than twice their ideal body weight to identify factors influencing left ventricular (LV) systolic function in morbidly obese patients and assess the effect of weight loss on LV systolic function. Patients were studied before and after weight loss induced by gastroplasty. The study cohort was 133 +/- 8% overweight before weight loss and 39 +/- 7% overweight at the nadir of weight loss. Before weight loss, LV fractional shortening varied inversely with LV internal dimension in diastole (an indirect index of preload), LV end-systolic wall stress and systolic blood pressure (indexes of afterload). The weight loss-induced change in LV fractional shortening varied directly with the pre-weight loss LV internal dimension in diastole, LV end-systolic wall stress and systolic blood pressure, and inversely with the pre-weight loss LV fractional shortening. The weight loss-induced change in LV fractional shortening varied inversely with the weight loss-induced changes in LV end-systolic stress and systolic blood pressure. In patients with reduced LV fractional shortening (n = 14), weight loss produced a significant increase in LV fractional shortening that was accompanied by a significant decrease in LV internal dimension in diastole, LV end-systolic stress and systolic blood pressure. The results suggest that LV loading conditions have an important role in determining LV systolic function in morbidly obese patients. Improvement in LV systolic function in these patients is closely related to weight loss-induced alterations in LV loading conditions.

Acute and long-term effects of nifedipine on pulmonary and systemic hemodynamics in patients with pulmonary hypertension associated with diffuse systemic sclerosis, the CREST syndrome and mixed connective tissue disease.

Ten patients with pulmonary hypertension associated with diffuse systemic sclerosis (1 patient), the CREST syndrome (calcinosis cutis, Reynaud's phenomenon, esophageal dysmotility, sclerodactyl, telangiectasia) (6 patients) and mixed connective tissue disease (3 patients) were studied to assess the effect of oral nifedipine on pulmonary and systemic hemodynamics. Each patient underwent right-sided cardiac catheterization just before nifedipine administration. Thereafter, oral nifedipine was administered in 10 mg increments every 90 minutes until pulmonary vascular resistance normalized or a total dose of 30 mg was achieved. Hemodynamic measurements were obtained at 30-minute intervals for 3 hours, then hourly for 9 hours (acute study). Hemodynamic studies were repeated 3 to 6 months after the initial catheterization with the minimum dose of oral nifedipine (administered every 8 hours) required to achieve maximal reduction of pulmonary vascular resistance in the acute study (long-term study). In the acute study, oral nifedipine produced a significant decrease in mean pulmonary vascular resistance from 6.3 +/- 3.8 to 4.3 +/- 3.6 U (p less than 0.001). Similar changes in pulmonary vascular resistance were noted in the long-term study (n = 6). The results indicate that oral nifedipine is capable of producing an acute and sustained reduction in pulmonary vascular resistance in patients with pulmonary hypertension associated with diffuse systemic sclerosis, the CREST syndrome and mixed connective tissue disease.

Effect of beta blockade with betaxolol on left ventricular systolic function in chronic stable angina pectoris and left ventricular dysfunction.

To assess the effect of beta blockade on left ventricular (LV) performance in patients with LV dysfunction and stable angina pectoris, 18 subjects taking a placebo followed by incremental doses of the cardioselective beta-adrenergic blocking agent betaxolol (5, 10, 20, 40 and 80 mg/day) were studied. The study ended with the achievement of optimal clinical beta blockade (heart rate at rest 50 to 60 beats/min, a 20% or smaller increase in heart rate during stage 1 of symptom-limited treadmill exercise using the modified Bruce protocol). Optimal clinical beta blockade produced a decrease in mean frequency of angina, from 6.8 +/- 1.7 to 0.7 +/- 0.8 episodes per week (p less than 0.0005) and an increase in mean treadmill exercise capacity, from 3.1 +/- 1.7 to 7.7 +/- 2.8 minutes (p less than 0.0005). LV systolic function was assessed at rest and during symptom-limited exercise with radionuclide left ventriculography. Mean LV ejection fraction (EF) during therapy with placebo was 39 +/- 7% at rest and 40 +/- 8% at peak exercise. Mean LVEF during optimal clinical beta blockade was 43 +/- 11% at rest and 45 +/- 10% at peak exercise. Neither of these changes was statistically significant. No patient had clinical or radiographic signs of LV failure. The results suggest that optimal clinical beta blockade with betaxolol, in doses sufficient to significantly reduce the frequency of angina and improve exercise capacity in patients with stable angina pectoris and mild to moderate LV systolic dysfunction, does not cause significant deterioration of LV systolic function or produce LV failure.

Effect of exercise and cavity size on right ventricular function in morbid obesity.

To assess the effect of exercise and to determine the influence of the right ventricular (RV) internal dimension on RV systolic function in morbid obesity, M-mode and 2-dimensional echocardiography and radionuclide ventriculography were performed on 22 patients whose body weight was at least twice the ideal body weight and who had no clinical or laboratory evidence of underlying organic heart disease or pulmonary disease. RV ejection fraction was measured at rest and during peak supine bicycle exercise. RV exercise response was defined as the change in RV ejection fraction during peak exercise. There was a significant negative correlation between percent over ideal body weight and RV exercise response (r = 0.86, p less than 0.00005) and between RV internal dimension and RV exercise response (r = 0.60, p less than 0.005). There were significant positive correlations between resting RV and left ventricular (LV) ejection fraction (r = 0.56, p less than 0.01) and between RV and LV exercise response (r = 0.70, p less than 0.0005). The subgroup with a high-normal or enlarged RV internal dimension (greater than or equal to 2.0 cm, n = 10) experienced no significant change in RV ejection fraction with exercise, whereas the subgroup whose RV internal dimension was less than 2.0 (n = 12) experienced a significant increase in RV ejection fraction from 44 +/- 10% at rest to 58 +/- 11% at peak exercise (p less than 0.03). The results suggest that in morbidly obese individuals without underlying cardiopulmonary disease RV dilatation may predispose to RV systolic dysfunction and assessment of RV systolic function should optimally include evaluation of RV exercise response.

The electrocardiogram in morbid obesity.

Electrocardiographic variables that occurred with significantly higher frequency in morbidly obese patients than in lean controls were low QRS voltage, leftward shift of the P, QRS, and T axes and multiple electrocardiographic criteria for left ventricular hypertrophy and left atrial enlargement. P-terminal force, RaVL, SaVR, and R/S ratio in lead V1 values were significantly higher in morbidly obese than in lean subjects.