Effect of a plant stanol ester-containing spread, placebo spread, or Mediterranean diet on estimated cardiovascular risk and lipid, inflammatory and haemostatic factors.

BACKGROUND AND AIMS: Mediterranean diet is associated with a reduced risk for cardiovascular disease (CVD). Use of plant stanols decreases low density lipoprotein cholesterol (LDL-C) concentrations. We compared the effects of the Mediterranean diet and plant stanol esters on vascular risk factors and estimated CVD (eCVD) risk. METHODS AND RESULTS: In this prospective, randomized, placebo-controlled study, 150 mildly hypercholesterolaemic subjects were randomized to Mediterranean diet, a spread containing plant stanol esters (2 g/day) or a placebo spread. Vascular risk factors were assessed every month for 4 months and the eCVD risk was calculated using the PROspective- Cardiovascular-Munster (PROCAM), Framingham, and Reynolds risk engines. Placebo had no significant effect on risk factors or eCVD risk. Mediterranean diet gradually induced a significant reduction in total cholesterol (TC), LDL-C, triglycerides, high sensitivity C-reactive protein (hsCRP), blood pressure and eCVD risk (24-32%). The plant stanol ester spread reduced (by 1 month) TC (-14%), LDL-C (-16%), hsCRP (-17%), and estimated CVD risk (26-30%). eCVD risk reduction was sustained at 4th months when the gradual Mediterranean diet eCVD risk reduction became comparable to that of the stanol group. CONCLUSIONS: Plant stanol esters yielded an early, by 1st treatment month, reduction of eCVD risk that resulted from a TC, LDL-C, and hsCRP decrease. eCVD risk reduction on the Mediterranean diet resulted from a change in several CVD risk factors and equaled that of plant stanol at 4 months. The consumption of plant stanol esters by moderately hypercholesterolaemic patients may be a useful option to reduce CVD risk in those who do not adopt a Mediterranean diet.

The prevalence of the metabolic syndrome in Greece: the MetS-Greece Multicentre Study.

BACKGROUND: The Third Report (ATP III) of the National Cholesterol Education Program Expert Panel (NCEP) highlighted the importance of identifying and treating patients with the metabolic syndrome (MetS) to prevent cardiovascular disease (CVD) and progression to diabetes mellitus. Limited information is available about the prevalence of MetS, as defined by the NCEP ATP III, in Europe, especially in Greece. OBJECTIVE: To estimate the prevalence of the MetS in Greece, The MetS-Greece Study. DESIGN AND PARTICIPANTS: A cross-sectional analysis of a representative sample of Greek adults (4153 participants older than 18 years). One group consisting of military personnel (n = 300) and another one from a Greek Muslim Community (n = 300) were used for comparison. In all, 4753 subjects were included in the final analysis. RESULTS: All subjects from the general population were Caucasian men (49%) and women (51%), living in urban (n = 2243, 54%), semi-urban (n = 1038, 25%) and rural (n = 872, 21%) areas. The age-standardized prevalence of the MetS was 23.6%[95% confidence interval (CI): 22.4-25.1%]. This was similar in men (24.2%, 95% CI: 22.3-25.2%) and women (22.8%, 95% CI: 21.4-25.0%) (p = 0.3). The prevalence increased with age in both sexes, 4.8% among participants aged 19-29 years and 43% for participants over 70 years old (p for trend < 0.0001). There was a 14.7-fold increase in odds ratio for having MetS in the age group > 70 years old compared with that of 19-29 years old (p < 0.0001) Most of those with MetS had three components of the syndrome (61%), 29% had four and 10% had all five components. Abdominal obesity (82%) and arterial hypertension (78%) were the most common abnormalities in both sexes. The Greek Muslim Community, on a high-saturated fat diet, had the highest prevalence of the MetS (35.2%, 95% CI: 30.4-40.3%), and the military group, with a high physical activity level and a diet 'close' to Mediterranean, had the lowest (9.4%, 95% CI: 6.2-13.1%). According to the 2001 Census, about 2.3 million Greeks may have the MetS. CONCLUSIONS: These results show that the MetS is highly prevalent in the Greek adult population. This may have major implications for the incidence of CVD. Promoting healthy diets, low caloric intake and physical activity must be urgently undertaken.

Effect of statins and ACE inhibitors alone and in combination on clinical outcome in patients with coronary heart disease.

We assessed the 'synergy' of statins and angiotensin-converting enzyme inhibitors (ACEI) in reducing vascular events in patients with coronary heart disease (CHD). The GREek Atorvastatin and CHD Evaluation (GREACE) Study, suggested that aggressive reduction of low density lipoprotein cholesterol to 2.59 mmol/l (<100 mg/dl) significantly reduces morbidity and mortality in CHD patients, in comparison to undertreated patients. In this post hoc analysis of GREACE the patients (n=1600) were divided into four groups according to long-term treatment: Group A (n=460 statin+ACEI), B (n=420; statin, no ACEI), C (n=371;no statin, on ACEI), and D (n=349; no statin, no ACEI). Analysis of variance was used to assess differences in the relative risk reduction (RRR) in 'all events' (primary end point) between groups. During the 3-year follow-up there were 292 cardiovascular events; 45 (10% of patients) in group A, 61 (14.5%) in group B, 91 in group C (24.5%) and 95 events in group D (27%). The RRR (95% confidence interval (CI) in the primary end point in group A was 31%, (95% CI -48 to -6%, P=0.01) in comparison to group B, 59% (95% CI -72 to -48%, P<0.0001) to group C and 63% (95% CI -74 to -51%, P<0.0001) to group D. There was no significant difference in RRR between groups C and D (9%, CI -27-10%, P=0.1). Other factors (eg the blood pressure) that can influence clinical outcome did not differ significantly between the four treatment groups. In conclusion, the statin+ACEI combination reduces cardiovascular events more than a statin alone and considerably more than an ACEI alone. Aggressive statin use in the absence of an ACEI also substantially reduced cardiovascular events. Treatment with an ACEI in the absence of a statin use reduced clinical events in comparison to patients not treated with an ACEI but not significantly, at least in these small groups of patients.

The effect of statins versus untreated dyslipidaemia on renal function in patients with coronary heart disease. A subgroup analysis of the Greek atorvastatin and coronary heart disease evaluation (GREACE) study.

BACKGROUND: Little is known about statins in the prevention of dyslipidaemia induced renal function decline. The secondary coronary heart disease (CHD) prevention GREACE study suggested that dose titration with atorvastatin (10-80 mg/day, mean dose 24 mg/day) achieves the national cholesterol educational programme treatment goals and significantly reduces morbidity and mortality, compared with usual care. AIMS: To report the effect of statin on renal function compared with untreated dyslipidaemia in both treatment groups. METHODS/RESULTS: All patients had plasma creatinine values within the reference range < 115 micro mol/litre (13 mg/litre). The on study creatinine clearance (CrCl), as estimated (for up to 48 months) by the Cockroft-Gault formula, was compared within and between treatment groups using analysis of variance to assess differences over time. Patients from both groups not treated with statins (704) showed a 5.2% decrease in CrCl (p < 0.0001). Usual care patients on various statins (97) had a 4.9% increase in CrCl (p = 0.003). Structured care patients on atorvastatin (783) had a 12% increase in CrCl (p < 0.0001). This effect was more prominent in the lower two quartiles of baseline CrCl and with higher atorvastatin doses. After adjustment for 25 predictors of all CHD related events, multivariate analysis revealed a hazards ratio of 0.84 (confidence interval 0.73 to 0.95; p = 0.003) with every 5% increase in CrCl. CONCLUSIONS: In untreated dyslipidaemic patients with CHD and normal renal function at baseline, CrCl declines over a period of three years. Statin treatment prevents this decline and significantly improves renal function, potentially offsetting an additional factor associated with CHD risk.

Heart rate variability after long-term treatment with atorvastatin in hypercholesterolaemic patients with or without coronary artery disease.

Low heart rate variability (HRV) level, indicative of impaired autonomic function, is associated with an increased risk of cardiovascular morbidity and mortality and is negatively affected by hypercholesterolaemia. In order to test the hypothesis that significant low density lipoprotein (LDL) cholesterol reduction after treatment with a statin will have a beneficial effect on HRV level in hypercholesterolaemic patients with or without coronary artery disease (CAD), forty consecutive patients (28 men and 12 women) with a median age of 61, range (17--70) years were studied. Twenty had stable CAD and 20 were free of CAD at baseline. Twenty healthy volunteers, of similar age and gender as the patients, were used as controls. Patients were treated with atorvastatin (20 mg/day) for 2 years. Changes in lipid parameters and HRV indices were assessed at baseline and 2 years later in all subjects. In both patient subgroups a significant beneficial change in all lipid parameters (more pronounced in the CAD+ subgroup) and a significant beneficial modification in HRV time and frequency domain indices was recorded (more pronounced in the CAD- subgroup), while lipid parameters and HRV indices remained unchanged in the control group. A correlation between LDL concentrations and most of the HRV indices was found at baseline in both patient subgroups, while no such correlation was found between values or their percent changes after hypolipidaemic treatment. These data suggest that treatment with atorvastatin improves autonomic function, as reflected by an increase in HRV level, and this may be a likely mechanism, at least in part, for the reduction in clinical events reported by the landmark survival studies with statins in primary and secondary CAD prevention. Perhaps, if this finding is confirmed by larger studies, HRV level may prove to be a useful tool for risk-stratification and treatment guide in high-risk patients with hypercholesterolaemia, regardless of CAD.

Atorvastatin plus pravastatin for the treatment of heterozygous familial hypercholesterolaemia--a pilot study.

The most common side-effect of statins, mainly during dose titration, is liver toxicity, In these cases, sufficient control of low density lipoprotein cholesterol (LDL-C) in patients with heterozygous familial hypercholesterolaemia (HFH) becomes problematical. In patients with intolerance to resins as well, especially in the presence of coronary artery disease (CAD), it is practically impossible to reach the LDL-C treatment goal. This study included seven HFH patients with CAD, who presented with alanine amino transferase levels greater than three times the upper normal limit during dose titration of atorvastatin or simvastatin of from 20 mg/day to 40 mg/day. They could not tolerate concomitant cholestyramine administration, and presented with LDL-C levels significantly higher than the treatment goal (100 mg/dl; 2.6 mmol/l). In these patients, a combination of two statins with different pharmacokinetics (20 mg/day of atorvastatin plus 40mg/day of pravastatin) was administered for a mean period of one year. Efficacy was compared with that of monotherapy with each drug alone and with that of 40 mg of atorvastatin in 13 patients, who could also not tolerate resin co-administration, and that of 40 mg/day of atorvastatin plus 12 g of cholestyramine in 30 patients, with similar pretreatment LDL-C levels. No increase in serum transaminases and no symptom or sign of myopathy was recorded during the administration of the combination of the two statins for a mean period of 12 months. The atorvastatin plus pravastatin regimen was more effective than both monotherapies and equally effective with the 40 mg of atorvastatin and the 40 mg of atorvastatin plus 12 g of cholestyramine regimens in reducing LDL-C (59% vs. 57% and 61%, respectively) and triglyceride levels (31% vs. 32% and 28%, respectively), while it also had a better effect on high density lipoprotein cholesterol (13% vs. 7% and 8%). The data suggest that the atorvastatin-pravastatin combination has a highly beneficial effect on all lipid parameters, without causing hepatotoxicity, in HFH patients with CAD who are sensitive to higher doses of statins in monotherapy. These results require confirmation in larger studies.

Effect of quinapril or metoprolol on circadian sympathetic and parasympathetic modulation after acute myocardial infarction.

Abnormal autonomic nervous system impairment in patients with acute myocardial infarction (AMI) has a circadian pattern with the greatest manifestation in the morning hours; it probably plays an important role in the pathogenesis of cardiac arrhythmias and acute ischemic syndromes. Angiotensin-converting enzyme inhibitors improve autonomic function in patients with AMI, but the circadian pattern of this effect has not been studied. Heart rate variability-normalized frequency domain indexes were assessed 5 days (baseline) after the onset of uncomplicated AMI and 30 days after therapy with quinapril (n = 30), metoprolol (n = 30), or placebo (n = 30) with a solid-state digital Holter monitor. Normal subjects (n = 30) were used as controls. Quinapril increased parasympathetic and decreased sympathetic modulation, and improved sympathovagal interactions manifested by an increase in normalized high-frequency power (HFP), and a decrease in normalized low-frequency power (LFP), and their ratio (LFP/HFP) during the entire 24-hour period (p<0.001), with maximal effect on the ratio (p<0.0001) between 02.00 to 04.00 A.M., 08.00 to 11.00 A.M., and 19.00 to 22.00 P.M. (delta% ratio -30%, -32%, and -26%, respectively). Metoprolol increased HFP and decreased LFP and the LFP/HFP ratio mainly between 08.00 A.M. to 12.00 noon, and 19.00 to 22.00 P.M. (delta% ratio -21%, and -12% respectively, p<0.001). Heart rate variability indexes in the placebo group and controls remained unchanged 30 days after the baseline study. In conclusion, quinapril increased parasympathetic, and decreased sympathetic and partially restored sympathovagal interaction in patients with uncomplicated AMI during the entire 24-hour period, with peak effect in the early and late morning and evening hours. Metoprolol had a similar effect during the late morning and evening hours, but at a lower level. These effects may prove beneficial in reducing cardiac arrhythmias and acute ischemic syndromes in past-AMI patients.

Long-term effect of converting enzyme inhibition on circadian sympathetic and parasympathetic modulation in patients with diabetic autonomic neuropathy.

OBJECTIVE: Autonomic nervous system function in patients with diabetes mellitus (DM), especially those with diabetic autonomic neuropathy (DAN), displays an abnormal circadian pattern compared to normal subjects; this probably plays an important role in the onset of acute cardiovascular syndromes, which display a similar pattern of occurrence with a blunted late morning peak, and an increase of episodes during the night, in comparison to non-diabetic subjects. This study was undertaken to investigate the effect of an angiotensin-converting enzyme inhibitor, quinapril, on the circadian pattern of heart rate variability (HRV), a reliable index of sympathovagal interactions, in patients with definite DAN. METHODS & RESULTS: Normalised HRV frequency domain indices [high frequency power (HFP), reflecting vagal tone, low frequency power (LFP), reflecting both vagal and sympathetic (predominantly) modulation, and their ratio (LFP/HFP), indicative of sympathovagal balance] were assessed in 60 patients with DAN at baseline and one year after therapy with quinapril (n = 30), or placebo (n = 30) on a 24-hour 2-channel electrocardiogram with a solid state Holter monitor. Normal subjects (n = 30) and patients with DM without DAN (n = 30), were used as controls. The baseline circadian variation of fractional normalised power in DAN patients was abolished, with pronounced dominance of LFP over HFP during the whole 24-hour period. After one year of treatment, quinapril increased HFP, decreased LFP and improved their ratio, in the morning (07.00 a.m. to 15.00 p.m.) and night (23.00 p.m. to 07.00 a.m.) time intervals, with maximal effect in the night time interval (HFP = 20%, LFP = -8%, LFP/HFP = -31%; for all comparisons p < 0.05 vs baseline values and p < 0.001 vs one year of placebo). CONCLUSIONS: Quinapril increased HFP and decreased LFP as well as their ratio, all indicative of sympathetic predominance reduction, in patients with DAN at time intervals these indices were most adversely affected (morning and night). Since autonomic function is an important contributor in the pathogenesis of acute coronary events, malignant arrhythmias and sudden cardiac death, improvement of indices related to autonomic function in DAN patients in these time intervals may prove beneficial in clinical practice.

Effect of aldose reductase inhibition on heart rate variability in patients with severe or moderate diabetic autonomic neuropathy.

Patients with diabetic autonomic neuropathy (DAN) have an increased cardiovascular mortality rate compared with diabetic patients without DAN. Heart rate variability (HRV) time and frequency domain indices are strong predictors of malignant arrhythmias and sudden cardiac death. This prospective, randomised, double-blind, placebo-controlled study analysed the long-term effect of an aldose reductase inhibitor, tolrestat, on HRV time and frequency domain variables in 45 patients with diabetes mellitus (DM) and DAN. Patients were randomised into tolrestat (n = 22) and placebo (n = 23) groups. Tolrestat (200 mg/day) or placebo were administered, respectively, for a period of 12 months. HRV was assessed at months 0, 3, 6, 9 and 12. The HRV level of the 45 patients was compared with that of 20 patients with DM, with analogous glycaemic control, without DAN and 20 healthy controls, of similar age and gender. At the twelfth month, tolrestat, compared with placebo, had a beneficial effect on HRV indices related to vagal tone. Compared with baseline, HRV time and frequency domain indices showed no significant improvement. Moreover, at the twelfth month of tolrestat administration, HRV indices remained less than that of patients with DM but without DAN, and healthy controls. The 12 patients of the 22 with moderate DAN benefited more than the 10 patients of the 22 with severe DAN. At the twelfth month no patient showed deterioration in HRV indices with tolrestat as was seen with placebo. Our data suggest that tolrestat slows down the progression of DAN compared with placebo. This effect of an aldose reductase inhibitor may contribute to a reduction in risk for malignant ventricular arrhythmias. The early detection of DAN is imperative for successful intervention.

Effect of Atorvastatin versus Simvastatin on Lipid Profile and Plasma Fibrinogen in Patients with Hypercholesterolaemia: A Pilot, Randomised, Double-Blind, Dose-Titrating Study.

OBJECTIVE: To investigate the effect of atorvastatin vs simvastatin on lipid profile and plasma fibrinogen in patients with hypercholesterolaemia. PATIENTS: 30 outpatients (25 men), with a median age of 51 years were studied. Eight patients had established coronary artery disease (CAD) and four had diabetes mellitus at baseline. 11 patients presented a Frederickson's IIb phenotype and 19 a IIa phenotype at baseline. STUDY DESIGN: After a 6-week placebo period, patients were randomly assigned to simvastatin (10 mg/day, n = 15) or atorvastatin (10 mg/day, n = 15). Lipid profile, apolipoproteins B and A-I and plasma fibrinogen were measured for a 16-week period, at 4-week intervals. Thereafter, the dose of each drug was doubled only in patients with low density lipoprotein cholesterol (LDL-C) levels above 130 mg/dl for a further 16-week period. RESULTS: Ten of 15 patients on atorvastatin 10mg (66%) and four of 15 on simvastatin 10mg (27%) achieved the LDL-C <130 mg/dl goal. Apolipoprotein B was reduced by both drugs (-33%, p < 0.001 for atorvastatin and -18%, p < 0.05 for simvastatin), but plasma fibrinogen and triglyceride were reduced only by atorvastatin (-20%, p < 0.01; -36%, p < 0.001, respectively). During the second 16-week period seven of 11 patients receiving the simvastatin 20mg dose (64%) achieved the LDL-C <130 mg/dl goal. The comparison of atorvastatin 10mg with simvastatin 20mg showed that the drugs appear to be equipotent in terms of LDL-C lowering. CONCLUSIONS: Atorvastatin in equipotent doses to simvastatin appeared to be more effective than the latter in reducing triglyceride and plasma fibrinogen in patients with hypercholesterolaemia, mainly in those with Frederickson's phenotype Iib.

Safety and efficacy of long-term statin-fibrate combinations in patients with refractory familial combined hyperlipidemia.

No monotherapy is able to tackle effectively all atherogenic features of familial combined hyperlipidemia: high low-density lipoprotein (LDL) cholesterol, triglycerides (TG), and plasma fibrinogen, as well as low high-density lipoprotein (HDL) cholesterol. The present study investigated the safety and efficacy of combined pravastotin or simvastatin with gemfibrozil or ciprofibrate treatment on total cholesterol, LDL, TG, plasma fibrinogen, and apoproteins B and A-I in patients with refractory familial combined hyperlipidemia, with or without coronary artery disease. From the initial 420 patients included in the study, 389 (294 men and 95 women, mean age 51 years [range 30 to 65]) completed the study. These patients were followed for a mean period of 29 months (1 year [n = 107], 2 years [n = 102], 3 years [n = 95], and 4 years [n = 85]). Patients given a hypolipidemic diet were randomly assigned to pravastatin + gemfibrozil (n = 135, 20 and 1,200 mg/day, respectively), simvastatin + gemfibrozil (n = 130, 20 and 1,200 mg), or simvastotin + ciprofibrate (n = 124, 20 and 100 mg). Lipid parameters, apoproteins B and A-I, and plasma fibrinogen were assessed every 3 months. Physical and laboratory investigations for adverse effects were performed every month for the first 3 months and every 3 months thereafter. No patient exhibited myopathy or rhabdomyolysis. Five patients (1.3%) were withdrawn from the study because of high transaminases (more than threefold the upper normal limit). Five nonfatal coronary artery disease events were recorded. All 3 combination treatments were more effective in normalizing lipid profile than any monotherapy in the past. Simvastatin + ciprofibrate was more effective than pravastatin + gemfibrozil in reducing LDL, TG, and plasma fibrinogen levels. Simvastatin + gemfibrozil increased HDL levels more than the other 2. The apoprotein B decrease was analogous to the LDL reduction by all combinations, whereas apoprotein A-I was increased more with simvastatin + gemfibrozil. The data suggest that the statin-fibrate combinations used in the study are safe and have a favorable effect on all major coronary artery disease risk factors in patients with refractory familial combined hyperlipidemia with or without coronary artery disease. Early detection of the rare drug-induced reversible hepatotoxicity calls for close monitoring of patients.

Effect of angiotensin-converting enzyme inhibitors on the power spectrum of heart rate variability in post-myocardial infarction patients.

BACKGROUND: Heart rate variability (HRV) time and frequency domain indices are strong predictors of malignant arrhythmias and sudden cardiac death. The effect of various angiotensin-converting enzyme (ACE) inhibitors on HRV in patients with acute myocardial infarction (AMI) has not been studied. METHODS: Ninety patients with uncomplicated AMI (age range 39-75 years, median 61 years) were assigned randomly to six groups of 15 patients each. They were treated with placebo or one of the following ACE inhibitors for 30 days: captopril, cilazapril, enalapril, lisinopril or quinapril. HRV was assessed 3 days after the onset of AMI (baseline), and 30 days after treatment. Fifteen patients with stable coronary artery disease and 15 healthy volunteers, age- and sex-matched with AMI patients, served as controls. RESULTS: At baseline, time and frequency domain HRV indices in the AMI groups were equally less than those in patients with stable coronary artery disease and normal volunteers. Compared with placebo, quinapril, lisinopril and captopril changed frequency domain HRV indices 30 days after initiation of treatment, indicating an increase in vagal tone, whereas enalapril and cilazapril had no significant effect on these indices. Most of the time domain HRV indices 30 days after initiation of treatment increased significantly in all patients treated with ACE inhibitors, but remained unchanged in the placebo group. Frequency domain and time domain HRV indices 30 days after treatment in the quinapril group did not differ statistically from those in patients with stable coronary artery disease, but were less than those in normal volunteers. CONCLUSIONS: Quinapril, lisinopril and captopril improved frequency domain HRV indices related to vagal tone, whereas cilazapril and enalapril had no effect on these indices. This influence of some ACE inhibitors on HRV may be beneficial in reducing the risk for sudden death in post-myocardial infarction patients.

Effect of chronic quinapril administration on heart rate variability in patients with diabetic autonomic neuropathy.

OBJECTIVE: Heart rate variability (HRV) time and frequency domain indexes are strong predictors of malignant arrhythmias and sudden cardiac death. Patients with diabetic autonomic neuropathy (DAN) have an increased cardiovascular mortality rate compared with diabetic patients without DAN. RESEARCH DESIGN AND METHODS: The present double-blind, randomized, and placebo-controlled study analyzed the effect of quinapril, an ACE inhibitor, on HRV time and frequency domain variables in patients with DAN. Forty patients (17 men and 23 women) of a mean age of 51 (range 19-68) years, free of coronary artery disease and arterial hypertension, were randomized into a quinapril or placebo group. HRV was recorded at months 0, 3, and 6. The parameters measured were 1) time domain indexes: SD of all 24-h R-R intervals (intervals between consecutive electrocardiogram R waves), or SDNN/24-h; mean of SD of R-R intervals of all 5-min segements (SDNN/5-min); root-mean-square of the differences of successive R-R intervals (RMSSD); and percentage of the R-R intervals differing more than 50 ms (pNN50); and 2) frequency domain indexes: total power (TP), high-frequency power (HFP), low-frequency power (LFP), and very-low-frequency power (VLFP). HRV level of the 40 patients were compared with one of 20 matched diabetic patients, of analogous glycemic control without DAN, and 20 healthy control subjects. RESULTS: Quinapril, compared with placebo, increased total HRV: SDNN/24-h (P < 0.05), TP (P < 0.05), and HRV parameters related to parasympathetic activity: pNN50 (P < 0.01). RMSSD (P < 0.05), and HFP in absolute and normalized units (P < 0.01). LFP/HFP ratio was decreased (P < 0.01). Despite the beneficial effect of quinapril on parasympathetic variables of HRV these remained less than those of diabetic patients without DAN and healthy control subjects. CONCLUSIONS: Our findings suggest that quinapril significantly increases parasympathetic activity in patients with DAN 3 months after treatment initiation and sustains this effect until the 6th month. This might contribute to the reduction of the risk for malignant ventricular arrhythmias in these patients.

Effects of simvastatin and ciprofibrate alone and in combination on lipid profile, plasma fibrinogen and low density lipoprotein particle structure and distribution in patients with familial combined hyperlipidaemia and coronary artery disease.

BACKGROUND: Hypolipidaemic agents do not usually normalize all of the multiple lipoprotein abnormalities in patients with familial combined hyperlipidaemia (FCHL). The effect of the simvastatin-ciprofibrate combination in comparison with each drug alone on the lipoprotein abnormality patterns was studied in patients with FCHL and coronary artery disease (CAD). METHODS: Sixty patients (53 men and seven women), mean age 52 years (range 36-60 years), were studied. After a 4-week placebo period, patients were randomly assigned to three groups. The first group (n = 20) received simvastatin (20 mg daily), the second group (n = 20) ciprofibrate (100 mg daily) and the third group (n = 20) the combination of both drugs for a 12-week period. Parameters measured were as follows: plasma fibrinogen, total cholesterol, triglycerides, low density lipoprotein (LDL), very low density lipoprotein, intermediate density lipoprotein, and high density lipoprotein cholesterol, as well as LDL subfraction distribution and structure by density gradient ultracentrifugation. Apoproteins (apo) B and AI were assessed by immunoturbidometry. RESULTS: At baseline, apoB, LDL cholesterol and triglycerides were increased, whereas LDL particles were small and dense. ApoB was significantly reduced by all three interventions. Drug combination and ciprofibrate significantly reduced plasma fibrinogen (-24 and -25%, respectively; P < 0.001) and triglycerides (-51 and -49%, respectively; P < 0.001). Drug combination and simvastatin significantly reduced LDL cholesterol (-25 and -22%, respectively; P < 0.001) compared with ciprofibrate (-10%; P < 0.01). Ciprofibrate and drug combination increased LDL particle size (parameter K -0.24 versus -0.61 and -0.30 versus -0.62, respectively; P < 0.001), whereas simvastatin had no significant effect on LDL particle size. The cholesterol content of LDL particles was reduced with ciprofibrate and the drug combination only in the dense LDL particles (LDL3-5) and increased in the light (LDL1-2) subfractions, whereas simvastatin reduced the cholesterol content of all LDL subfractions except LDL2. Ciprofibrate and drug combination reduced the triglyceride content of all LDL subfractions. CONCLUSION: Combined treatment with simvastatin and ciprofibrate effectively reduced plasma fibrinogen, triglycerides, total and LDL cholesterol and increased LDL particle size in patients with FCHL and CAD. These effects might induce a clinical benefit for these patients.

Effect of quinapril or metoprolol on heart rate variability in post-myocardial infarction patients.

The effect of quinapril or metoprolol on heart rate variability (HRV) indexes was studied in patients who had recovered from acute myocardial infarction. Patients with stable coronary artery disease and normal volunteers were used as controls. Sixty patients with uncomplicated myocardial infarction (aged 32 to 74 years [mean 56.7]) were randomized to quinapril (n = 25), metoprolol (n = 25), and placebo (n = 10). HRV was assessed 5 days (baseline) and 35 days after the onset of acute myocardial infarction. After the baseline studies, the post-myocardial infarction patients were treated with metoprolol (50 to 100 mg/day), quinapril (5 to 10 mg/day), or placebo. Twenty patients with stable coronary artery disease and 20 healthy volunteers, age- and sex-matched to myocardial infarction patients, were used as controls. Compared with placebo, quinapril and metoprolol increased HRV indexes significantly 35 days after the onset of myocardial infarction. HRV indexes were not statistically different between the 2 treatment groups. At baseline and after therapy, HRV was similar in patients with anterior or inferior wall myocardial infarction. HRV 35 days after the onset of myocardial infarction was not different from HRV in patients with stable coronary artery disease, but was decreased when compared with that in normal volunteers. Data suggest that quinapril has the same beneficial effect on HRV indexes as metoprolol in patients who have recovered from uncomplicated acute myocardial infarction.

Holt-Oram syndrome with malformations of renal and cerebral arteries.

The case of a 40-year-old woman with Holt-Oram syndrome is presented. Besides the absence of thumbs and an atrial septal defect, she presented multiple strokes and end-stage renal failure. The latter might be attributed to malformations of the arteries of the brain and kidneys within the expression of the syndrome, despite the small possibility of coincidence.

Long-term effect of gemfibrozil on coronary heart disease risk profile of patients with primary combined hyperlipidaemia.

BACKGROUND: The purpose of the present study was to assess the effect of gemfibrozil on 12 independent coronary heart disease risk factors in patients with primary combined hyperlipidaemia. METHODS: One hundred and five patients (62 men and 43 women), aged 53.2 +/- 4.8 years, were studied. The 10-year probability of myocardial infarction for the patients was calculated using the TYPMI (Ten-Year Probability for Myocardial Infarction) computer program, which is constructed to co-evaluate 12 independent coronary artery disease risk factors. All patients followed a lipid-lowering diet and placebo for 3 months. At month 0, the patients received 1200 mg gemfibrozil daily, divided into two equal doses, for a period of 12 months. At months -3, 0, 1, 3, 6, and 12, total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides [only if the low-density lipoprotein (LDL) cholesterol to high-density lipoprotein cholesterol ratio was above 5], systolic blood pressure, plasma glucose, left ventricular mass index, and plasma fibrinogen were measured. Smoking habits, sex, age, physical activity and family history of coronary heart disease were also evaluated. The mean 10-year probability of myocardial infarction of all 105 patients at month 0 was 27.8%. This was significantly higher than the anticipated probability (10.4%, P < 0.001), resulting from an age- and sex-matched group of general population. RESULTS: During the third month of treatment, the following changes were recorded: total cholesterol -17%, LDL cholesterol -18%, very-low-density lipoprotein (VLDL) cholesterol -45%, HDL cholesterol 20%, triglycerides -43%, apoprotein B -12%, apoprotein A-I 9% and plasma fibrinogen -21%. The estimated risk for myocardial infarction was reduced to 13.5% (delta m = -51%). All changes were significant and sustained until the twelfth treatment month. None of the patients were withdrawn from the study because of adverse effects of the treatment. CONCLUSION: Gemfibrozil reduces the estimated risk for myocardial infarction in patients with primary combined hyperlipidaemia at a level no different from the one of the general population. This beneficial effect of gemfibrozil, which was expressed by the third month and was evident for some time afterwards, was attributed to a significant reduction of triglyceride and fibrinogen levels, an increase of HDL cholesterol concentrations and a moderate decrease of total cholesterol and LDL cholesterol levels.