Relationship between phospholipid transfer protein activity and HDL level and size among inbred mouse strains

Site-directed mutagenesis was used to investigate the loading of iron into rat liver ferritin by ceruloplasmin. Changes were made in the H chain to investigate the role of tyrosines involved in an inherent ferroxidase activity thought to be involved in the self-loading of iron into ferritin. Mutation Y34F affected the rate of iron loading by ceruloplasmin and incorporation of the oxidized iron into the core. Mutation Y29R (making it analogous to the L chain) had no effect on iron oxidation but slightly decreased core formation. A double mutation in the L chain, to open the alpha-helix bundle channel, and R25Y, making the protein more analogous to the H chain, increased the amount of iron incorporated into the core, again suggesting that this Tyr is involved in ligand exchange for core formation. Additional changes in the L chain involving the BC loop suggest that the entire BC loop is involved in the association of ferritin with ceruloplasmin, increasing its ferroxidase activity and the rate of iron loading into ferritin.     

Adenovirus mediated overexpression of human phospholipid transfer protein alters plasma HDL levels in mice

To study the function of plasma phospholipid transfer protein (PLTP) in vivo, a liver directed adenoviral gene transfer system was used to overexpress human PLTP in mice. For the experiments, two strains of mice, wild type (C57/B1) and mice transgenic for the human apoA-I gene (HuApoA-ITg), were utilized. Five days after injection of the recombinant PLTP adenovirus, wild type mice showed a 4-fold increase in serum PLTP activity in (12.2+/-1.3 micromol/ml per h to 48.1+/-8.6 micromol/ml per h (+394%), P < 0.001). The PLTP overexpression induced significant reduction of serum cholesterol (2.46+/-0.08 to 0.69+/-0.42 mmol/l (-72%), P < 0.001), phospholipids (3.10+/-0.06 to 0.90+/-0.24 mmol/l (-71%), P < 0.01), and triglycerides (0.2+/-0.07 to 0.08+/-0.03 mmol/l (-69%), (P < 0.001). ApoA-I was hardly detectable in the serum. These lipid changes were due to a dramatic reduction of high density lipoprotein (HDL). The HuApoA-ITg mice displayed higher basal HDL level and PLTP activity. Adenovirus mediated PLTP overexpression in these mice resulted in a similar decrease of the lipid levels as that seen in the C57/B1 mice. However, the lipoprotein profile revealed a redistribution of HDL, with the appearance of larger buoyant HDL species. The results demonstrate that plasma phospholipid transfer protein in vivo causes high density lipoprotein (HDL) conversion and thereby plays a central role in HDL metabolism.     

High density lipoprotein conversion mediated by human plasma phospholipid transfer protein

Phospholipid transfer protein (PLTP) was purified from lipoprotein-free human plasma, obtained upon treatment of plasma with dextran sulfate and Ca2+, by employing a series of column chromatography. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the purified PLTP showed a single main band, corresponding to the molecular mass of 78 kDa. However, isoelectric focusing of the purified preparation gave multiple bands with pI ranging from 4.3 to 5.1, indicative of microheterogeneity. Purified PLTP was shown to possess not only phospholipid transfer activity, but also high density lipoprotein (HDL) conversion activity (Tu, A.-Y., Nishida, H. I., and Nishida, T. (1990), FASEB J. 4, A2148; Jauhiainen, M., Metso, J., Pahlman, R., Blomqvist, S., van Tol, A., and Ehnholm, C. (1993) J. Biol. Chem. 268, 4032-4036). Isolated HDL3 was enlarged to the size of HDL2b upon incubation with purified PLTP for 6 h at 37 degrees C at the PLTP/HDL3 molar ratio of approximately 1:45. Both the HDL conversion and the phosphatidylcholine transfer activities of purified PLTP were effectively inhibited by rabbit anti-PLTP immunoglobulin G. The primary importance of PLTP in the HDL enlargement that occurs in human plasma upon incubation at 37 degrees C was shown by the strong inhibitory effect of the anti-PLTP immunoglobulin G. The process of PLTP-mediated HDL enlargement was accompanied by the release of apoproteins, primarily apoA-I. HDL3 enlargement mediated by PLTP was effectively inhibited by the addition of free fatty acids.     

Relationship between acute diarrhoea and low plasma levels of vitamin A and retinol binding protein

OBJECTIVE: We studied possible sex differences of the effect of fenofibrate on serum lipoproteins. Twenty-three patients with primary hypercholesterolaemia (10 postmenopausal women and 13 aged-matched men) were treated with slow-release fenofibrate for 96 weeks. RESULTS: Steady state lipoprotein concentrations were reached after 12 and 24 weeks of treatment in women and men, respectively. During the subsequent follow-up the lipoprotein concentrations remained constant. In women total and low-density lipoprotein (LDL) cholesterol decreased from 299 to 234 mg.dl-1 and from 210 to 151 mg.dl-1, respectively, and in men from 265 to 233 mg.dl-1 and from 192 to 160 mg.dl-1. The decrease in triglycerides was also more pronounced in women (-42%) than in men (-18%). High-density lipoprotein (HDL) cholesterol increased significantly in women from 53 to 63 mg.dl-1 but not in men (45 to 50 mg.dl-1). Since the changes in LDL and HDL cholesterol occurred in opposite directions, the decrease in LDL/HDL cholesterol ratio was accentuated in both groups. However, this ratio was decreased almost twofold in women (-41%) compared to men (-23%). Although the serum concentrations of fenofibric acid were 1.3-fold higher in women than in men, which was probably due to the higher body weight in men (1.2-fold), this difference can hardly explain the favorable effect on lipoproteins in women. CONCLUSION: The present study indicates that fenofibrate might be very effective by reducing the concentrations of atherogenic lipoproteins in postmenopausal women.     

Remodeling of HDL by phospholipid transfer protein: demonstration of particle fusion by 1H NMR spectroscopy

There is evidence that phospholipid transfer protein (PLTP) can increase reverse cholesterol transport by inducing favorable subclass distribution in the high density lipoprotein (HDL) fraction. This includes generation of initial cholesterol acceptor particles, pre beta-HDL, and of enlarged particles that are rapidly cleared from the circulation. However, partly because of methodological difficulties, the mechanisms behind the PLTP-mediated interconversion of HDL particles are not fully understood. In this communication, we describe the use of a novel methodology, based on 1H NMR spectroscopy, to study the PLTP-induced size changes in the HDL particles. In accordance with native gradient gel electrophoresis, the 1H NMR data revealed a gradual production of enlarged HDL particles in the HDL3+ PLTP mixtures. In addition, according to a physical model for lipoprotein particles, relating the frequency shifts observable with NMR to the size of the lipoprotein particles, the NMR data demonstrated that PLTP-mediated HDL remodeling involves fusion of the HDL particles.     

Relationship between serum angiotensin-converting enzyme activity and plasma plasminogen activator inhibitor activity in patients with recent myocardial infarction

BACKGROUND: An elevated level of angiotensin-converting enzyme (ACE) has been demonstrated to increase the risk of myocardial infarction. Plasminogen activator inhibitor (PAI) is the most important physiological inhibitor of tissue plasminogen activator in plasma. An elevated level of PAI has been reported to be associated with decreased fibrinolytic capacity and to constitute a marker of the risk for recurrent coronary thrombosis. METHODS: We measured the serum ACE activity and plasma PAI activity in 34 patients with recent myocardial infarction, and evaluated the correlation between these two values by linear regression analysis. We also administered captopril (37.5 mg/day) to 17 of these patients and placebo to the other 17 patients at random, and compared the changes in PAI activity and ACE activity in these two groups over a 1-month period. RESULTS: There was a significant correlation between the serum ACE activity and the plasma PAI activity at baseline in the patients (r = 0.498, P < 0.01). The captopril-treated patients showed significantly reduced PAI activity (P < 0.01), and a concomitant decrease in ACE activity. CONCLUSION: These results suggest that elevated ACE activity is associated with impaired fibrinolysis and that treatment with an ACE inhibitor improves the fibrinolytic function in patients with recent myocardial infarction. The results also suggest that the renin-angiotensin system plays a role in the increased risk of ischemic cardiovascular events when it is activated, and in the reduction of risk of recurrent myocardial infarction by ACE inhibition.     

Opposite effects of cholesteryl ester transfer protein and phospholipid transfer protein on the size distribution of plasma high density lipoproteins. Physiological relevance in alcoholic patients

The aim of the present study was to investigate the role of the cholesteryl ester transfer protein (CETP) and the phospholipid transfer protein (PLTP) in determining the size distribution of high density lipoproteins (HDL) in human plasma. Whereas both purified CETP and PLTP preparations were able to promote the size redistribution of isolated HDL3, CETP favored the emergence of small HDL, while PLTP induced the formation of both small and large conversion products. When the total plasma lipoprotein fractions isolated from nine distinct subjects were incubated for 24 h at 37 degrees C with either purified PLTP or purified CETP, significant alterations in the relative proportions of the five distinct plasma HDL subpopulations, i.e., HDL2b (9.71-12.90 nm), HDL2a (8.77-9.71 nm), HDL3a (8.17-8.77 nm), HDL3b (7.76-8.17 nm), and HDL3c (7.21-7. 76 nm) were also observed. PLTP induced a significant increase in the relative abundance of HDL2b (8.66 +/- 2.34% versus 7.87 +/- 1. 83% in controls; p < 0.01) and a significant decrease in the relative abundance of HDL3a (32.76 +/- 3.42% versus 37.87 +/- 2.62% in controls; p < 0.05). In contrast, CETP significantly reduced the relative proportion of HDL2a (33.03 +/- 2.53% versus 37.56 +/- 6.43% in controls; p < 0.01) but significantly increased the relative proportion of both HDL3b (21.36 +/- 6.97% versus 15.58 +/- 7.75% in controls; p < 0.01) and HDL3c (3.21 +/- 4.84% versus 1.13 +/- 0.56% in controls; p < 0.05). Finally, in order to assess further the physiological relevance of in vitro observations, CETP activity, PLTP activity, and HDL size distribution were determined in plasmas from 33 alcoholic patients entering a cessation program. Alcohol withdrawal was associated with (i) a significant increase in plasma CETP activity (173.5 +/- 70.5%/h/ml before versus 223.2 +/- 69. 3%/h/ml after alcohol withdrawal, p = 0.0007), (ii) a significant reduction in plasma PLTP activity (473.9 +/- 203.7%/h/ml before versus 312.7 +/- 148.4%/h/ml after alcohol withdrawal, p = 0.0001), and (iii) a significant shift of large HDL2b and HDL2a toward small HDL3b and HDL3c. On the one hand, changes in plasma CETP activity correlated negatively with changes in the proportion of HDL2a (r = -0.597, p = 0.0002) and positively with changes in the proportion of HDL3b (r = 0.457, p = 0.0075). On the other hand, changes in plasma PLTP activity correlated positively with changes in the proportion of HDL2b (r = 0.482, p = 0.0045) and negatively with changes in the proportion of HDL3a (r = -0.418, p = 0.0154). Taken together, data of the present study revealed that plasma PLTP and CETP can exert opposite effects on the size distribution of plasma HDL. PLTP can promote the formation of HDL2b particles at the expense of HDL3a, while CETP can promote the formation of HDL3b particles at the expense of HDL2a.     

Human cholesteryl ester transfer protein measured by enzyme-linked immunosorbent assay with two monoclonal antibodies against rabbit cholesteryl ester transfer protein: plasma cholesteryl ester transfer protein and lipoproteins among Japanese hypercholesterolemic patients

Plasma cholesteryl ester transfer protein (CETP) concentrations were measured in Japanese subjects by an ELISA with two different monoclonal antibodies that were raised against rabbit CETP and cross-reacted against human CETP. Among 63 patients who consecutively underwent coronary angiography, the plasma CETP of 37 patients with luminal stenosis > or = 50% in their coronary arteries was not significantly different from that of the 26 patients with luminal stenosis < 50%. No other lipoprotein-related measurement except HDL-cholesterol differentiated the two groups. Among 40 hypercholesterolemic patients, no lipoprotein-related measurement other than LDL-cholesterol was found to positive correlate with the CETP. Before and after the treatment of 23 patients with simvastatin 5 mg a day for 4 weeks, plasma CETP markedly decreased in those whose pretreatment CETP was > or = 3 mg/L; no change was observed for those with lower pretreatment CETP. In the former group, negative correlation between CETP and HDL-cholesterol was demonstrated only in the posttreatment plasma.     

Low levels of HDL cholesterol in hypothyroid patients with cardiovascular diseases

BACKGROUND: Hypothyroidism is a frequent cause of hyperlipidemia, particularly in women, but its true prevalence, both in the general population and in dyslipidemic subjects, is unknown. It is uncertain if low thyroid function significantly influence HDL metabolism and if sub-clinical disease may cause metabolic abnormalities and increase cardiovascular risk. METHODS: Three-hundred and three consecutive female patients (mean age 59.2 +/- 0.5 yrs), observed in a metabolic ward because of dyslipidemia, were evaluated. RESULTS: Forty-three women (14.1% of the total) showed sub-clinical hypothyroidism, while in 12 cases (4.0%) overt hypothyroidism was diagnosed; 8 further women (2.6%) had been previously diagnosed to be hypothyroid and were under hormone replacement therapy. On the whole, hypothyroid patients showed higher mean triglyceride levels and lower HDL-cholesterol than dyslipidemic euthyroid women, but the difference did not reach statistical significance. Total cholesterol concentration did not change with impaired thyroid function. Hypothyroid patients reported a clinical history of cardiovascular disease, or had severe atherosclerosis demonstrated, more often than euthyroid subjects (25.0% vs 19.7%, p = n.s.). When only women with arterial disease were considered, HDL plasma levels were significantly lower in the hypothyroid than in the euthyroid group (44.3 +/- 3.1 vs 56.2 +/- 1.7 mg/dl, respectively; p < 0.01). Hypertriglyceridemia and obesity often coexisted. CONCLUSIONS: In conclusion, among dyslipidemic women, unrecognised hypothyroidism is highly prevalent (both sub-clinical and manifest). In hypothyroid subjects atherosclerosis seem to associate with particularly low HDL plasma levels. This might precede atherosclerosis development (reinforced by concomitant thyroid failure) and represent a marker of the polymetabolic syndrome.     

Influence of plasma cholesteryl ester transfer activity on the LDL and HDL distribution profiles in normolipidemic subjects

The relations of cholesteryl ester transfer protein (CETP) activity to the distribution of low density lipoproteins (LDLs) and high density lipoproteins (HDLs) were investigated in fasting plasma samples from 27 normolipidemic subjects. LDL and HDL subfractions were separated by electrophoresis on 20-160 g/L and 40-300 g/L polyacrylamide gradient gels, respectively. Subjects were subdivided into two groups according to their LDL pattern. Monodisperse patterns were characterized by the presence of a single LDL band, whereas polydisperse patterns were characterized by the presence of several LDL bands of different sizes. To investigate the influence of lipid transfers on LDL patterns, total plasma was incubated at 37 degrees C in the absence of lecithin:cholesterol acyltransferase (LCAT) activity. The incubation induced a progressive transformation of polydisperse patterns into monodisperse patterns. Under the same conditions, initially monodisperse patterns remained unchanged. Measurements of the rate of radiolabeled cholesteryl esters transferred from HDL3s to very low density lipoproteins (VLDLs) and LDLs revealed that subjects with a monodisperse LDL pattern presented a significantly higher plasma CETP activity than subjects with a polydisperse LDL pattern (301 +/- 85%/hr per milliliter versus 216 +/- 47%/hr per milliliter, respectively; p < 0.02). In addition, when total plasma was incubated for 24 hours at 37 degrees C in the absence of LCAT activity, the relative mass of cholesteryl esters transferred from HDLs to apolipoprotein B-containing lipoproteins was greater in plasma with monodisperse LDL than in plasma with polydisperse LDL (0.23 +/- 0.06 versus 0.17 +/- 0.06, respectively; p < 0.02). These results indicated that in normolipidemic plasma, CETP could play an important role in determining the size distribution of LDL particles. The analysis of lipoprotein cholesterol distribution in the two groups of subjects sustained this hypothesis. Indeed, HDL cholesterol levels, the HDL:VLDL+LDL cholesterol ratio, and the esterified cholesterol:triglyceride ratio in HDL were significantly lower in plasma with the monodisperse LDL pattern than in plasma with the polydisperse LDL pattern (p < 0.01, p < 0.01, and p < 0.02, respectively). Plasma LCAT activity did not differ in the two groups. Plasma CETP activity correlated positively with the level of HDL3b (r = 0.542, p < 0.01) in the entire study population. Whereas plasma LCAT activity correlated negatively with the level of HDL2b (r = -0.455, p < 0.05) and positively with the levels of HDL2a (r = 0.475, p < 0.05) and HDL3a (r = 0.485, p < 0.05), no significant relation was observed with the level of HDL3b.(ABSTRACT TRUNCATED AT 400 WORDS)     

Relationship between plasma aldosterone concentration and plasma potassium in patients with essential hypertension during alprenolol treatment

Plasma aldosterone concentration (PAC), plasma renin concentration (PRC), plasma potassium, plasma sodium and blood pressure (BP) have been measured in 22 patients with essential hypertension before and after treatment for one month with alprenolol. PAC, PRC and BP decreased and plasma potassium increased significantly during treatment. Plasma sodium, however, was unchanged. Changes in PAC were inversely correlated to changes in plasma potassium. No relationship could be demonstrated between PAC and plasma sodium. Mean BP was inversely correlated to PAC during alprenolol treatment, but bot before treatment. No relationship was found between changes in BP and changes in PRC. The results suggest that plasma potassium is an important regulatory factor for aldosterone secretion during alprenolol treatment. Other factors, however, must have a modulating influence and since the renin- angiotensin system is not suppressed to very low values, this system is possibly the most important of these factors. It is suggested that aldosterone secretion is not of primary importance in BP regulation during alprenolol treatment.     

Dietary pectin with high viscosity lowers plasma and liver cholesterol concentration and plasma cholesteryl ester transfer protein activity in hamsters

The aim of this retrospective cohort study was to investigate whether survival of patients with breast cancer has changed over the period 1975-89. A total of 2604 women diagnosed as having invasive breast cancer at a clinical oncology unit in London were followed up for between 5 and 20 years. Patients were divided into four groups according to menstrual status (pre or post) and the staging of cancer (operable or inoperable). For each group, survival from diagnosis was compared between three consecutive 5-year cohorts, both with and without adjustments made for relevant prognostic factors. No temporal patterns were found in patients with inoperable cancer, in whom the survival rate was consistently low. Of women with operable cancers, differences were seen only among post-menopausal women, for whom the best survival patterns were seen in patients diagnosed between 1985-89. This is probably due to tamoxifen being commonly prescribed as adjuvant treatment for this cohort of patients. We cannot explain an apparently worse survival in the group of patients presenting in the early 1980s compared with that observed in the late 1970s.     

Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels

Plasma high density lipoprotein (HDL) levels are strongly genetically determined and show a general inverse relationship with coronary heart disease (CHD). The cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to other lipoproteins and is a key participant in the reverse transport of cholesterol from the periphery to the liver. A high prevalence of two different CETP gene mutations (D442G, 5.1%; intron 14G:A, 0.5%), was found in 3,469 men of Japanese ancestry in the Honolulu Heart Program and mutations were associated with decreased CETP (-35%) and increased HDL chol levels (+10% for D442G). However, the overall prevalence of definite CHD was 21% in men with mutations and 16% in men without mutations. The relative risk (RR) of CHD was 1.43 in men with mutations (P < .05); after adjustment for CHD risk factors, the RR was 1.55 (P = .02); after additional adjustment for HDL levels, the RR was 1.68 (P = .008). Similar RR values were obtained for the D442G mutation alone. Increased CHD in men with mutations was primarily observed for HDL chol 41-60 mg/dl; for HDL chol > 60 mg/dl men with and without mutations had low CHD prevalence. Thus, genetic CETP deficiency appears to be an independent risk factor for CHD, primarily due to increased CHD prevalence in men with the D442G mutation and HDL cholesterol between 41 and 60 mg/dl. The findings suggest that both HDL concentration and the dynamics of cholesterol transport through HDL (i.e., reverse cholesterol transport) determine the anti-atherogenicity of the HDL fraction.     

Differences between plasma and serum complement in patients with chronic liver disease

Of sixty patients with chronic liver disease, eight with cirrhosis or chronic hepatitis had very low serum CH50 but normal plasma CH50. The complement component profiles of these sera revealed markedly decreased C4 and C2 activities and normal C3T (C3-C9) activities. From these results, it is suggested that the early acting complement components had been non-specifically activated during blood coagulation in these patients. No difference between plasma and serum CH50 was found in patients with hepatitis B(s) antigen.     

Antithrombin III, protein C and protein S plasma levels in patients with Beh?et's disease

The association between natural inhibitors of coagulation and thrombophilia was investigated in 35 patients with Behcet's disease. Antithrombin III and protein C levels were measured using synthetic chromogenic substrate methods, and protein S levels by quantitative enzyme-linked immunosorbent assay. There were no significant differences between patients and controls in plasma antithrombin III, protein C and free protein S concentrations. We conclude that there was no evidence of a primary coagulation inhibitor abnormality in patients with Beh?et's disease.     

Relationship between insulin sensitivity and dehydroepiandrosterone sulfate in patients with ischemic heart disease

Schools are settings with high concentrations of young people with little exposure to Mycobacterium tuberculosis and greater risk of developing disease when infection occurs as the result of sporadic localized outbreaks. We studied two outbreaks in two elementary schools (A and B) after two cases of bacilliferous pulmonary tuberculosis were detected in teachers in 1990 and 1994. Contacts were trace din school A by the primary care physician and in school B by the pneumologist and public health authorities. Contacts were classified as belonging to the risk group (RG) or the low risk group (LRG). The RG was composed of 187 contacts in school A and 59 in school B. Individuals in the LRG numbered 429 and 116 respectively. Mantoux positives numbered 108 in the RG and 45 in the LRG in school A (p < 0.001). In school B 50 RG individuals and 29 LRG individuals were positive (p < 0.001). The proportion of Mantoux positives was greater in the RG of school B than in the RG of school A (p < 0.01), probably owing to longer time of evolution of disease and possible laryngeal involvement in the index case. Likewise, tuberculin positives were fewer in the LRG of school A than in the LRG of school B (p < 0.001), owing to the small size of the LRG in school A. Thirteen cases of tuberculosis were seen in school A, six of which called for drug prophylaxis after contacts were traced. The nature of the index case and the conditions of exposure are both important in such outbreaks, demonstrating the need to act appropriately to trace contacts, preferably under the supervision of a pneumologists.     

Suppression of plasma cholesteryl ester transfer protein activity in acute hyperinsulinemia and effect of plasma nonesterified fatty acid

Cholesteryl ester transfer protein (CETP) is a major determinant of the plasma high-density lipoprotein cholesterol (HDL-C) level and plays an important role in the reverse cholesterol transport system. The purpose of this study was to determine the effect of acute hyperinsulinemia on plasma CETP activity in normal subjects and patients with non-insulin-dependent diabetes mellitus (NIDDM). Hyperinsulinemia was achieved using the hyperinsulinemic-euglycemic clamp. CETP activity was determined as the transfer of radiolabeled cholesterol in HDL3 to acceptor lipoprotein. Mean plasma CETP activity during an insulin infusion in both subject groups was significantly decreased compared with the mean basal activity. Suppression of plasma CETP activity in the NIDDM patients was significantly less than in the normal subjects (-4.2% +/- 7.9% v -9.6% +/- 6.4%, P < .02). Regression analysis showed that this suppression was correlated with plasma nonesterified fatty acid (NEFA) levels after the clamp and with the magnitude of the NEFA decrease (r = .318, P < .02 and r = .292, P < .05, respectively). The data suggest that acute hyperinsulinemia reduces plasma CETP activity through a decrease in plasma NEFA.     

Providing dental treatment for patients with cardiovascular disease

The appropriate management of dental patients with cardiovascular disease is contingent on appropriate assessment and evaluation. Baseline vital signs, a good medical history and medical evaluation are all essential for the safe delivery of care. All patients with cardiovascular disease can be managed using the following guidelines: 1. Properly assess the patient. This should include an assessment by the dentist and also a medical consultation if required. 2. Establish what medications the patient is taking along with the dose and timing and note any potential drug interactions and side effects. 3. Use short appointments (less than one hour), preferably in the morning. 4. Premedication should be considered to alleviate anxiety. The intraoperative use of nitrous oxide and oxygen is also a reasonable strategy for patients with cardiovascular disease, particularly those with ischemic heart disease. 5. Effective local anesthesia is important in order to avoid undue stress during the appointment as long as the guidelines for the administration of epinephrine are followed. The use of epinephrine impregnated gingival displacement cord should be strictly avoided in patients with cardiovascular disease. 6. For patients with angina pectoris, a fresh supply of nitroglycerin should be available at the time of the appointment. Prophylactic nitroglycerin has been shown to be effective in the prevention of both hypertension and angina pectoris during dental treatment. The appointment should be terminated early if the patient becomes overly anxious. In the event of cardiovascular symptoms during dental treatment, all work should be stopped. Emergency measures should be instituted if necessary. Preparations for emergencies should be undertaken by all dentists. The treatment of patients with cardiovascular disease is relatively simple if the proper steps are taken. The use of blood pressure measurements on all patients will help to screen for undiagnosed hypertension and all patients who are potentially hypertensive should be referred for medical evaluation. A preventive approach to the treatment of these patients will serve to prevent untoward outcomes and provide safe and simple delivery of dental care for cardiovascular patients.     

Fibrinolytic response in subjects with hypertriglyceridemia and low HDL cholesterol

The combination of hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) appears to be an excessively high risk factor for coronary artery disease (CAD). In the Helsinki study, both coronary events and mortality were decreased by gemfibrozil, especially in subjects with low HDL-C and high triglycerides (TG). On the other hand, it is known that high levels of TG can be associated with high levels of circulating plasminogen activator inhibitor (PAI), which is also a possible risk factor for CAD. The aim of the present study was to see: 1) whether the combination of low HDL-C and high TG is associated with a more impaired fibrinolytic response than in either isolated condition, and 2) whether gemfibrozil administration can improve fibrinolysis in patients with both high TG and low HDL-C. Twelve non-obese, non-diabetic subjects (eight men, four women; mean age 55 +/- 13 yrs) with low HDL-C (< 35 mg/dL men; < 45 mg/dL women) and high TG (mean 253.6 +/- 42.6 mg/dL) entered the study (Group A). Additionally fourteen comparable subjects with normal HDL-C were also investigated (Group B), plus 12 comparable subjects with isolated low HDL-C (Group C). Ten healthy people served as the control group. The following plasma fibrinolytic parameters were measured: tissue plasminogen activator antigen, PAI antigen and activity, euglobulin fibrinolytic activity (EFA) on fibrin plates, plasminogen and alpha-2-antiplasmin activities. All except the latter two values were also measured after venous occlusion (vo). In baseline conditions, patients in Groups A and B had higher EFA values before vo and higher PAI-1 antigen and alpha-2-antiplasmin levels after vo than those of controls or the subjects in Group C. The relationship between PAI antigen and PAI activity and TG was not confirmed in our population (n = 48). We also saw no interference due to HDL-C, while there was a significant relationship between EFA before vo and both TG and cholesterol. After gemfibrozil treatment (600 mg bid for 12 weeks), the lipid profiles of subjects with high TG and low HDL-C were significantly improved. There was also a slight reduction of PAI activity after vo, while the PAI-1 antigen had decreased significantly from baseline after vo (56.3 +/- 13 ng/mL before vo; 48.4 +/- 21 ng/mL after vo; P = 0.04). The higher risk of CAD in patients with low HDL-C and high TG might be in part related to impairment of fibrinolysis, which occurs in patients with isolated high TG. The close relationship existing between both TG and cholesterol levels and fibrinolytic activity confirm the key role of this latter process in the development of CAD.