Moshe Weintraub

Clearance of chylomicron remnants in normolipidaemic patients with coronary artery disease: case control study over three years

Abstract Objective: To test the hypothesis that subjects who clear chylomicron remnants slowly from plasma may be at higher risk of coronary artery disease than indicated by their fasting plasma lipid concentrations. Design: Case control study over three years. Setting: An 800 bed general municipal hospital. Subjects: 85 normolipidaemic patients with coronary artery disease selected prospectively and matched with 85 normolipidaemic subjects with normal coronary arteries on angiography. Interventions: All subjects were given a vitamin A fat loading test which specifically labels intestinal lipoproteins with retinyl palmitate. Main outcome measure: Postprandial lipoprotein metabolism. Results: The area below the chylomicron remnant retinyl palmitate curve was significantly increased in the coronary artery disease group as compared with the controls (mean 23.4 (SD 15.0) v 15.3 (8.9) µmol/l.h; 95% confidence interval of difference 4.37 to 11.82). Conclusions: Normolipidaemic patients with coronary artery disease had significantly higher concentrations of chylomicron remnants in plasma than normolipidaemic subjects with normal coronary vessels. This may explain the mechanism underlying the susceptibility to atherosclerosis of coronary artery disease patients with normal fasting lipid values. As diet and drugs can ameliorate the accumulation of postprandial lipoproteins in plasma, the concentration of chylomicron remnants should be measured in patients at high risk of coronary artery disease. Key messages Key messages The atherogenic effect of postprandial lipoproteins is hypothesised to be inversely related to their metabolic capacity Patients with coronary artery disease have decreased metabolic capacity of chylomicron remnants as compared with subjects with normal coronary arteries An ensuing postprandial dyslipidaemia may exist in patients with coronary artery disease who have normal fasting lipid values A vitamin A fat loading test may be useful in identifying these patients

Alleviating Constipation in the Elderly Improves Lower Urinary Tract Symptoms

Background: Constipation and lower urinary tract symptoms (LUTS) very frequently occur in the elderly, and several reports have suggested that dysfunction in either one of these systems may affect the other. Most studies correlating rectal and bladder dysfunction, however, have been carried out in children or young women. Objective: To examine the effect of alleviating constipation on LUTS in the elderly. Methods: Fifty-two patients aged 65–89 (mean 72 ± 13) years with chronic constipation and LUTS participated in this prospective cohort study. Before treatment of constipation was initiated and on their monthly visits, patients completed a questionnaire regarding their constipation pattern, urinary symptoms, sexual function and mood, and underwent urinalysis. Urinary tract anatomy and residual urine were evaluated by abdominal ultrasound at the commencement and completion of the study. Patients were followed up for 4 months. Results: Treatment of constipation increased the number of weekly defecations from 1.5 ± 0.9 to 4.7 ± 1.2 (p < 0.001). Patients spent less time on the toilet (25 ± 2.1 versus 63 ± 1.9 min, p < 0.0001). Fewer patients reported urgency (16 versus 34, p < 0.001), frequency (25 versus 47, p < 0.001) and burning sensation during urination (6 versus 17, p < 0.05). There was improvement in the scoring of urgency, frequency and burning sensation (from a baseline of 52 to 126, 131 and 95, respectively, p < 0.001). Urinary stream disturbances improved in 32 of the 52 patients (p < 0.001). Residual urine volume decreased from 85 ± 39.5 to 30 ± 22.56 ml (p < 0.001). There was also a significant decrease in the number of patients with bacteriurial events (5 versus 17, p < 0.001), and an improvement in sexual activity and mood (p < 0.05). Conclusions: Our data demonstrated that medical relief of constipation significantly improves LUTS in the elderly which, in turn, improves the patient’s mood, sexual activity and quality of life.

Transthoracic monitoring of the impedance of the right lung in patients with cardiogenic pulmonary edema.

Objective To evaluate the suitability of the new electrical impedance monitor RS-205 for monitoring of cardiogenic pulmonary edema (CPE). Design Prospective, controlled study. Setting A department of internal medicine in a 1,200-bed university-affiliated, teaching hospital. Patients Sixty patients, aged 52–80 yrs, 30 without CPE (controls) and 30 with or at high risk for CPE. Interventions Internal thoracic impedance (ITI) was monitored by the RS-205. The RS-205 is approximately three times more sensitive than the Kubicek monitor, and it eliminates the effect of the drift of skin-to-electrode impedance. This is achieved by eliminating skin electrode impedance by a special algorithm, thus allowing measurement of ITI rather than total transthoracic impedance. Measuring ITI, the main component of which is lung impedance, is a noninvasive and safe method. CPE was diagnosed in accordance with well-accepted clinical and roentgenological criteria. Measurements and Main Results The controls’ initial ITI was 68.3 ± 12.38 ohms. During 6 hrs of monitoring, the ITI attained a minimum average value of −1.3 ± 2.08% and a maximum average value of 4.6 ± 3.56% relative to baseline. In all patients entering CPE, ITI decreased by 14.4 ± 5.42% on the average (p < .001) 1 hr before the appearance of clinical symptoms. In patients with evolving CPE, ITI decreased significantly compared with controls (22.25 ± 9.82%, p < .001). In patients at the peak of pulmonary edema, ITI was 2.1 times lower than in the control group (33.1 ± 10.90 ohms, p < .001). In the last hour before the resolution of CPE, ITI increased in all patients by 17.7 ± 19.74% compared with the peak of disease (p < .05). After the resolution of pulmonary edema, ITI increased in all patients by 44.14 ± 26.90% compared with the peak of disease (p < .001). Importantly, the trend in ITI in all patients changed in accordance with the dynamics of CPE. A mixed general linear model shows that ITI values correlated well with the degree of crepitation, a direct characteristics of CPE. Conclusions The RS-205 is suitable for monitoring patients at high risk of CPE development. It enables detection of CPE and the monitoring of patients at all stages of CPE.

Seasonal Changes in Blood Pressure and Frequency of Related Complications in Elderly Israeli Patients with Essential Hypertension

Background: Earlier studies on hypertension demonstrated seasonal variations in different age groups. However, slightly greater fluctuations were found in the hypertensive elderly. Objective: We conducted a prospective 5-year study from January 1997 to December 2001 to evaluate the seasonal variation in blood pressure and the variables of age, gender, body mass index and related complications in elderly Israeli patients with essential hypertension. Methods: Blood pressure was measured in four seasons in 182 patients (98 men and 84 women; age range 65–91 years) treated for hypertension in our outpatient clinic. Results: Both systolic and diastolic mean blood pressures were higher during winter compared to summer (165 ± 11.6 and 90 ± 13.7 and 134 ± 47.3 and 74 ± 8.5 mm Hg, respectively; p < 0.001). There were no significant seasonal differences between spring and autumn or any correlation between the seasonal winter-summer difference in blood pressure and other studied parameters. Patients aged 65–75 years were unexpectedly more sensitive to winter-summer changes than older patients. There was a correlation between a large winter-summer difference in systolic blood pressure and a body mass index between 20 and 30, but there was none in lower or higher ranges. Supplementary antihypertension treatment was required during winter in 38% of these selected patients. Complications such as myocardial infarctions and strokes occurred twice as frequently in winter than in any other season (p < 0.0001). Conclusions: Both systolic and diastolic blood pressures were highest during winter. Hypertension complications were more frequent in winter. Our results refute those of earlier studies that failed to find significant seasonal variations in blood pressure among the elderly.

Acute effect of latanoprost on pulsatile ocular blood flow in normal eyes

PURPOSE To determine the effect of an acute dose of 0.005% latanoprost on intraocular pressure and pulsatile ocular blood flow in normal eyes. METHODS Nineteen volunteers received a single dose (two drops) of latanoprost 0.005% in one eye and placebo in the fellow control eye, randomized and masked to the observer. Intraocular pressure, perfusion pressure, pulsatile ocular blood flow, and systemic circulatory parameters were measured before and 8 hours after dosing. RESULTS The mean (+/- SE) intraocular pressure, perfusion pressure, and pulsatile ocular blood flow before treatment were 17 +/- 1 mm Hg, 46 +/- 3 mm Hg, and 13 +/- 1 microl per second, respectively, in both the treated and control eyes. The mean intraocular pressure reduction was 4.9 and 2.1 mm Hg (28% and 12%) in the treated and fellow eye, respectively. The mean perfusion pressure increase was 5.6 and 2.8 mm Hg (12% and 6%) in the treated and fellow eye, respectively. The mean pulsatile ocular blood flow increase was 2.7 and 0.2 microl per second (20% and 1%) in the treated and fellow eye, respectively. The treated eye change in pulsatile ocular blood flow was not correlated to the change in perfusion pressure. Simultaneous reduction of intraocular pressure and increase or no significant change in pulsatile ocular blood flow occurred in 15 of 19 (79%) of the treated eyes. The systemic blood pressure and pulse rates remained in normal ranges over the 8-hour period. CONCLUSION In this study, topical latanoprost significantly reduces intraocular pressure and increases ocular blood flow in normal eyes 8 hours after dosing. These effects of latanoprost may be beneficial in the management of glaucoma patients.

Hormone replacement therapy enhances postprandial lipid metabolism in postmenopausal women

Postmenopausal estrogen therapy reduces cardiovascular morbidity and mortality, except in women with advanced coronary disease. This beneficial effect is partly attributed to a reduction of fasting plasma total and low-density lipoprotein cholesterol (LDL-C) and an elevation of plasma high-density lipoprotein cholesterol (HDL-C) concentrations. Since postprandial lipemia seems to play a role in the pathogenesis of coronary artery disease, we evaluated the effect of hormone replacement therapy (HRT) on postprandial lipoprotein metabolism in 14 normolipemic postmenopausal women. A vitamin A fat-loading test before and after three cycles of treatment with a sequential combination of conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) was used to label chylomicrons and chylomicron remnants with retinyl palmitate (RP), and RP clearance was assessed over an 8-hour period postprandially. Following 3 months of HRT, fasting total cholesterol and LDL-C levels were reduced 9.8% (P = .049) and 16.5% (P = .023), respectively. Fasting HDL-C levels increased 18.9% (P = .001). Fasting triglycerides (TGs) increased, but not significantly. Postprandial integrated plasma TGs did not change significantly. The integrated RP levels in whole plasma and chylomicron (Svedberg flotation units [Sf] > 1,000) and nonchylomicron (Sf < 1,000) fractions were reduced 58% (P = .043), 78% (P = .041), and 75% (P = .001), respectively, after hormonal treatment. Enhanced clearance of chylomicrons and chylomicron remnants by HRT may contribute to the protective effect of estrogens against cardiovascular disease in normolipemic postmenopausal women.

The association of bile acid excretion and atherosclerotic coronary artery disease.

Background: Excess cholesterol is usually eliminated from the body by conversion to bile acids excreted in feces as bile salts. The excretion of large amounts of bile protects against atherosclerosis, while diminished excretion may lead to coronary artery disease (CAD). Objective: To investigate a relationship between CAD and bile acid excretion. Methods: Bile acid excretion was compared between 36 patients with proven CAD and 37 CAD-free individuals (controls). The groups were comparable for demographics and selected risk factors. All subjects received a 4-day standard diet that included ∼500 mg of cholesterol. Fecal bile acids from 24-hour stool collections were measured by gas liquid chromatography. Results: CAD patients excreted lower amounts of total bile acids (358 ± 156 mg) than controls (617 ± 293 mg; p < 0.01) and less deoxycholic acid (188.29 ± 98.12 mg versus 325.96 ± 198.57 mg; p < 0.0001) and less lithocholic acid (115.43 ± 71.89 mg versus 197.27 ± 126.87 mg; p < 0.01). Advanced age, male gender, left ventricular ejection fraction and total bile acid levels were significant independent factors that predicted CAD (p < 0.05). Mortality, CAD and cerebrovascular accident development rates were significantly lower for the controls at the 13-year follow up. Conclusion: CAD patients have significantly decreased bile acid excretion levels than non-CAD patients. An impaired ability to excrete cholesterol may be an additional risk factor for CAD development.

Metformin Enhances Clearance of Chylomicrons and Chylomicron Remnants in Nondiabetic Mildly Overweight Glucose-Intolerant Subjects

OBJECTIVE To assess the effect of metformin on the metabolism of intestinally derived lipoproteins in nondiabetic individuals who were mildly overweight and glucose intolerant. RESEARCH DESIGN AND METHODS A total of nine subjects with a BMI ≥ 25 kg/m2 and fasting serum glucose ≤ 6.1 mmol/l and who were glucose intolerant were studied. The subjects underwent a vitamin A fat-loading test before and after a 3-month treatment with 850 mg metformin twice a day. The metabolic behavior of the postprandial lipoproteins was compared with that found in a group of 19 healthy normolipidemic individuals who participated in a previous study. RESULTS Mean total plasma, chylomicron fraction, and nonchylomicron fraction retinyl palmitate (RP) pretreatment levels were 3.4-fold, 3.59-fold, and 3-fold higher, respectively, in the study group than in the normolipidemic group and were reduced by 50, 56, and 32%, respectively, after 3 months of metformin treatment. The decrease of chylomicron levels after treatment was positively correlated to the fasting triglyceride values before treatment (r = 0.73, P = 0.039) and to the serum insulin level at 120 min of standard glucose loading before treatment (r = 0.91, P = 0.002). CONCLUSIONS Metformin was shown to be beneficial in the clearance of postprandial lipoproteins in nondiabetic individuals who were mildly overweight and glucose intolerant.

Baseline Low-Density Lipoprotein Cholesterol Levels and Outcome in Patients With Heart Failure

The incidence of heart failure (HF) is constantly increasing in the Western world. Treatment with statins is well established for the primary and secondary prevention of cardiac events by lowering low-density lipoprotein (LDL) cholesterol levels. There are conflicting reports on the role of LDL cholesterol as an adverse prognostic predictor in patients with advanced HF. The aim of this study was to investigate the association between LDL cholesterol levels and clinical outcomes in 297 patients with severe HF (average New York Heart Association class 2.8). The mean follow-up period was 3.7 years (range 8 months to 11.5 years), and 37% of the patients died during follow-up. The mean time to first hospital admission for HF was 25 +/- 17 months. The study group was divided according to plasma LDL level < or =89, >89 to < or =115, >115 mg/dl. Patients with the highest baseline LDL cholesterol levels had significantly improved outcomes, whereas those with the lowest LDL cholesterol levels had the highest mortality. When analyzed with respect to statin use, it emerged that the negative association between LDL cholesterol level and mortality was present only in the patients with HF who were treated with statins. In conclusion, lower LDL cholesterol levels appear to predict less favorable outcomes in patients with HF, particularly those taking statins, raising questions about the need for aggressive LDL cholesterol-lowering strategy in patients with HF, regardless of its cause.

Methylphenidate Has Positive Hypocholesterolemic and Hypotriglyceridemic Effects: New Data

Many psychotropic drugs may affect plasma lipids profile and their metabolism, with carbamazepine being the best known among them. Methylphenidate is a piperidine derivative structurally related to amphetamines and acts as a central nervous system stimulant. Its effect on lipid metabolism has not been investigated. The authors evaluated how methylphenidate affects the lipid profile in the plasma of patients diagnosed as having attention‐deficit hyperactivity disorder (ADHD). All consecutive patients undergoing treatment for ADHD at the Adolescent Psychiatric Clinic (2003–2007) were enrolled. Blood samples for total cholesterol, low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), triglycerides, apolipoprotein A, apolipoprotein B, and lipoprotein (a) (Lp(a)) were collected before starting treatment and after 3 months of continuous treatment. Forty‐two patients (22 men), median age 16, participated. The median total cholesterol count decreased by 9 mg/dL (P < .0002), LDL‐C decreased by 5.0 mg/dL (P < .016), and triglycerides decreased by 8.0 mg/dL (P < .016). Changes in the levels of HDL‐C, apolipoprotein A, and apolipoprotein B were nonsignificant, and Lp(a) levels decreased by 2.0 mg/dL (P < .0007). Methylphenidate improves the lipid profile by decreasing total cholesterol, triglycerides, LDL‐C, and Lp(a).