Effect of hypertension and risk factors on diameters of abdominal aorta and common iliac and femoral arteries in middle-aged hypertensive and control subjects: a cross-sectional systematic study with duplex ultrasound.

There is a general tendency towards atherosclerosis and arterial dilatation in older age, and high blood pressure also tends to increase arterial diameters. The purpose of this study was to examine the effect of hypertension and other cardiovascular risk factors on aortic, common iliac and common femoral artery diameters. The diameters of the abdominal aorta and the iliac and femoral arteries and the extent of echogenic plaques in the aorta and the iliac arteries down to groin level were evaluated with ultrasound in 1007 middle-aged (40-60 years) men (505) and women (502), 496 with arterial hypertension and 511 controls. Twenty-eight subjects were excluded because of poor visualization. Men had significantly larger diameters of the abdominal aorta (mean 21.3+/-2.8 vs. 17.8+/-1.3 mm) and the common iliac (13.4+/-2.0 vs. 12.2+/-1.2) and common femoral arteries (11.0+/-1.4 vs. 9.7+/-0.9) than women (P for all <0.001), but arterial diameter was also related to the subject's size. Atherosclerotic plaques, age and height were associated with the diameter of the abdominal aorta in men, while high body mass index (BMI) had less significance. The diameter of the aorta was larger in hypertensive men aged 56-60 than in controls of the same age. In women, height, BMI and diastolic blood pressure (DBP) were associated with the diameter of the aorta, while systolic blood pressure (SBP) had less and age no effect. Age, plaques, height, BMI, DBP and SBP were associated with the diameters of the common iliac arteries in both genders, while smoking had an inverse correlation. The results on lipid values were inconsistent and an abnormal glucose tolerance test proved nonsignificant. In conclusion, arterial size measured as a diameter related to the subject's size was larger in men. Age, arterial plaques and blood pressure increased arterial diameter significantly. However, the hypertensive disease itself had only a minimal effect. The changes were smaller in women than in men.

Heart rate variability and progression of coronary atherosclerosis.

Low heart rate (HR) variability is associated with increased risk of cardiovascular morbidity and mortality, but the causes and mechanisms of this association are not well known. This prospective study was designed to test the hypothesis that reduced HR variability is related to progression of coronary atherosclerosis. Average HR and HR variability were analyzed in 12-hour ambulatory ECG recordings from 265 qualified patients participating in a multicenter study to evaluate the angiographic progression of coronary artery disease in patients with prior coronary artery bypass surgery and low high-density lipoprotein cholesterol concentrations (<1.1 mmol/L). Participants were randomized to receive a placebo or gemfibrozil therapy. The progression of coronary atherosclerosis was estimated by quantitative, computer-assisted analysis of coronary artery stenoses from the baseline angiograms and from repeated angiograms performed an average of 32 months later. The progression of focal coronary atherosclerosis of the patients randomized to placebo therapy was more marked in the tertile with the lowest standard deviation of all normal to normal R-R intervals (SDNN, 74+/-13 ms; mean decrease in the per-patient minimum luminal diameter -0.17 mm; 95% confidence interval [CI], -0.23 to -0.12 mm) than in the middle tertile (SDNN, 107+/-7 ms; mean decrease -0.05 mm; 95% CI, -0.08 to -0.01 mm) or highest tertile (SDNN, 145+/-25 ms; mean change 0.01 mm; 95% CI, -0. 04 to 0.02 mm) (P<0.001 between the tertiles). This association was abolished by gemfibrozil. SDNN was lower (P<0.001) and minimum HR was faster (P<0.01) in the patients with marked progression than in those with regression of focal coronary atherosclerosis. In multiple regression analysis including HR variability, minimum HR, demographic and clinical variables, smoking, blood pressure, glucose, lipid measurements and lipid-modifying therapy, progression of focal coronary atherosclerosis was independently predicted by the SDNN (beta=0.24; P=0.0001). Low HR variability analyzed from ambulatory ECG predicts rapid progression of coronary artery disease. HR variability provided information on progression of focal coronary atherosclerosis beyond that obtained by traditional risk markers of atherosclerosis.

Cholesterol lowering after participation in the Scandinavian Simvastatin Survival Study (4S) in Finland.

BACKGROUND: Patient compliance is crucial for the effectiveness of preventive medication. The aim of the study was to investigate changes in serum cholesterol levels and the use of cholesterol lowering drugs one year after the end of the Scandinavian Simvastatin Survival Study (4S), a randomized secondary prevention study of coronary heart disease with simvastatin and placebo. METHODS AND RESULTS: A questionnaire asking the current use of cholesterol lowering drugs, most recent serum cholesterol value and attitudes towards cholesterol lowering was sent to 785 surviving 4S participants in four 4S centres in Finland. The response rate was 94%. The current use of cholesterol lowering drugs and the reported mean serum cholesterol values were similar to the original simvastatin and placebo groups. In all, 74% (n = 546) reported that they had used cholesterol lowering drugs after the study, and 63% (n = 467) were currently using them, mostly simvastatin (96%) with an average dose of 14 (SD 5) mg.day-1. Cholesterol lowering was considered to be 'very important' by 53% and 'important' by 37% of the respondents. The most frequent reasons for discontinuation were 'drug costs' (38%) and 'normal cholesterol values' (30%). The reported mean serum cholesterol levels were 5.1 (SD 1.0) and 5.7 (SD 1.1) mmol-1 in the current cholesterol lowering drug users and non-users, respectively (P < 0.0001). The in-trial treatment goal of serum cholesterol (< or = 5.2 mmol-1) was not met in 38% of the users and in 68% of the non-users of cholesterol lowering drugs. CONCLUSION: One year post-trial the original simvastatin and placebo groups of the 4S had become similar with regard to the use of cholesterol lowering drugs and serum cholesterol levels. The adherence to medication, however, still remained relatively high, but there was a shift toward lower doses, and consequently toward higher post-trial serum cholesterol levels.

Prevalence of carotid atherosclerosis in middle-aged hypertensive and control subjects. A cross-sectional systematic study with duplex ultrasound.

BACKGROUND: Arterial hypertension has been found to increase atherosclerotic lesions, although contradictory results have suggested that hypertension has little or no effect. These discrepancies are probably caused by differences in populations. OBJECTIVE: To examine the effect of hypertension on carotid atherosclerosis in a population-based series of patients with an established diagnosis of arterial hypertension and controls. METHODS: Carotid intima-media thickness (IMT) and plaques were evaluated with duplex ultrasound in 1031 middle-aged (aged 40-60 years) men (n = 511) and women (n = 520), 513 with arterial hypertension and 518 controls. IMT was measured in the internal carotid artery, bifurcation and proximal, middle and distal common carotid artery, determining mean and maximal values for each patient. RESULT: Male sex, age, smoking and cholesterol were the most significant risk factors for combined plaque and intima-media thickness (CPIMT); hypertension and and abnormal glucose test result were further significant risk factors. There was a significant difference in CPIMT between the hypertensive and control subjects, but this was caused by the differences in the men; there were no statistically significant differences among the women. Plaques were found more frequently in the hypertensive men than they were in their controls (62.8 versus 49.8%), the corresponding percentages for the hypertensive and control women being 38.0 and 32.1%. There was a larger proportion of male subjects with a long duration of hypertension (> or = 7 years) who had plaques and greater CPIMT than there was of those with a short duration of hypertension. CONCLUSION: Hypertension had a significant effect on CPIMT and on the prevalence of plaques in men, but its effect in women was not significant. A long duration of hypertension resulted in greater CPIMT values and a higher prevalence of plaques, particularly in men.

The effects of monounsaturated-fat enriched diet and polyunsaturated-fat enriched diet on lipid and glucose metabolism in subjects with impaired glucose tolerance.

OBJECTIVE AND SUBJECTS: The effects of a high-fat, monounsaturated-fat enriched (Mono) diet and a reduced-fat, polyunsaturated-fat enriched (Poly) diet on lipid and glucose metabolism were compared in 31 subjects with impaired glucose tolerance. DESIGN AND INTERVENTIONS: After 3 weeks on a Run-in diet (37; 18:11:5, indicating energy percentages from total fat; saturated:monounsaturated:polyunsaturated fatty acids in the actual diets) subjects were randomized into a Poly-diet (34; 11:10:10) or a Mono-diet (40; 11:19:8) for 8 weeks. RESULTS: In the Mono group fasting plasma glucose (mean +/- SD) was lower after the test diet than after the run-in period (6.4 +/- 1.3 vs 6.0 +/- 0.8 mmol/L, 0 vs 8 weeks, P = 0.008), but remained unchanged in the Poly group (6.2 +/- 0.6 vs 6.1 +/- 0.7 mmol/L). Glucose effectiveness (SG), insulin sensitivity index and the first phase insulin response in an intravenous glucose tolerance test did not change significantly during either of the diets, but at the end of the study SG was higher in the Mono group than in the Poly group (P = 0.013). Serum total cholesterol, LDL cholesterol, and apolipoprotein B decreased in the Mono group, while in the Poly group only serum total cholesterol decreased significantly. However, the mean changes in serum lipids and lipoproteins did not differ significantly between the groups. CONCLUSIONS: In free-living subjects with impaired glucose tolerance both the Mono-diet and the Poly-diet consumed after a saturated-fat enriched Run-in diet improved serum lipid profile and the Mono-diet seemed to improve glucose metabolism as well.

Modification of VLDL apoprotein B by acetaldehyde alters apoprotein B metabolism.

Acetaldehyde (AcA), the first metabolite in ethanol oxidation, is chemically highly reactive and forms adducts with proteins in alcoholics. We examined the effect of very low density lipoprotein (VLDL) apoprotein B (apoB) modification by AcA on the metabolism of apoB-containing lipoproteins [VLDL, intermediate density lipoprotein (IDL) and low density lipoprotein (LDL)]. VLDL-B was selectively radiolabelled with either 125I or 131I and modified with various AcA concentrations, and the preparation was injected into rabbits simultaneously with control-treated VLDL. AcA modification of VLDL-B reduced the fractional catabolic rates for VLDL-B, IDL-B, and LDL-B. The direct removal of VLDL-B from plasma was decreased, whereas the fraction of VLDL-B converted to IDL-B was increased. The effect of AcA modification on the overall fraction of VLDL converted to LDL was qualitatively heterogeneous: VLDL-B modification with 2.0 mM AcA reduced the fraction converted, whereas modification with 4.0 and 8.0 mM AcA increased it. The concentrations of AcA used were higher than those reported in blood after ethanol ingestion, but the experiments serve to test in qualitative terms the model of VLDL-B modification by AcA. The observed VLDL-B alteration by AcA in vivo in alcoholics is most likely to be close to the minor modification used here, thereby theoretically contributing to the low IDL and LDL levels observed in alcoholics.

Relation of coronary heart disease and apolipoprotein E phenotype in patients with non-insulin dependent diabetes.

OBJECTIVES: To examine the relation between coronary heart disease and the apolipoprotein E phenotypes in patients with non-insulin dependent diabetes mellitus. DESIGN: Cross sectional study. SETTING: District around Kuopio University Central Hospital, East Finland. SUBJECTS: 138 men with non-insulin dependent diabetes and 64 men without diabetes as controls. MAIN OUTCOME MEASURE: Apolipoprotein E phenotype, electrocardiographic abnormalities, other signs of coronary heart disease. RESULTS: The prevalences of definite myocardial infarction and ischaemic electrocardiographic changes were highest in the diabetic men with the phenotypes E4/4 or E4/3 (25% (95% confidence interval 18% to 32%) and 50% (42% to 58%) respectively), although the difference between the phenotype groups was not significant. The prevalence of angina pectoris was 69% (61% to 77%) in men with the phenotypes E4/4 or E4/3 (p = 0.005 compared with other phenotypes), 41% (33% to 49%) in men with phenotype E3/3, and 47% (39% to 55%) in those with phenotypes E2/2 or E2/3. Similarly, the simultaneous presence of angina pectoris and ischaemic electrocardiographic changes was highest in the diabetic men with the phenotypes E4/4 or E4/3 (42% v 22% in those with E3/3 and 29% in those with E2/2, E2/3; p = 0.038). Overall, the prevalence of any evidence of coronary heart disease among the diabetic subjects with the phenotypes E4/4 or E4/3 was 81% (p = 0.011 compared with other phenotypes), 58% in those with phenotype E3/3, and 53% in those with phenotypes E2/2 or E3/3. CONCLUSION: Apolipoprotein E phenotypes E4/4 and E4/3 modulate the risk of coronary heart disease in men with non-insulin dependent diabetes.

Effect of erythromycin on the oro-caecal transit time in man.

Erythromycins often cause gastrointestinal side-effects due to an increase in motility or to change in the intestinal bacterial flora. In order to evaluate the effect of erythromycin on gastrointestinal motility. 11 healthy volunteers were given placebo, erythromycin stearate (ES) 1000 mg or a therapeutically equivalent single dose of erythromycin acistrate (EA.2'-acetyl erythromycin stearate) 800 mg in a double-blind trial. The oro-caecal transit time was measured using the hydrogen breath test with lactulose as the substrate. The transit time was estimated from the H2-peak (ppm) in end-expiratory breath by two methods, t1 representing the "front" and t2 the "bulk" of lactulose reaching the colon. t1 was 51 min in the placebo group, 38 min in the EA and 31 min in the ES group (p less than 0.05, ES vs placebo). t2 was 74 min, 64 min, and 46 min, respectively (p less than 0.05, ES vs placebo). The difference between EA and ES was also significant. Six subjects in the ES group but none in the EA group recorded adverse gastrointestinal effects attributable to medication. It was concluded that erythromycin shortens the oro-caecal transit time in man and that EA effects the transit time slightly less than ES.

Hostility as a risk factor for mortality and ischemic heart disease in men.

We report the association between hostility and the incidence of ischemic heart disease (IHD) in 3,750 Finnish men aged 40-59. Hostility was assessed from self-ratings on irritability, ease of anger-arousal, and argumentativeness, and four groups were formed from the summed hostility ratings. At baseline, the age-adjusted relative risk (RR) of the prevalence of angina pectoris between the highest and lowest hostility groups was 2.88 (95% confidence limits (CL), range 1.71-4.77). A three-year follow-up yielded 65 deaths and 109 IHD-incident cases. Hostility did not predict IHD among healthy men, but among men with previous IHD and hypertension (N = 104), the age-adjusted RR of IHD between the highest and lowest hostility groups was 12.9 (95% CL, 3.92-42.6). After standardization for smoking, obesity, heavy alcohol use, and snoring, the RR was 14.6 (95% CL, 1.94-110). When the degree of dyspnea at baseline was also standardized, the RR was 21.1 (95% CL, 1.59-282). Our data suggest that extreme hostility is not a consequence of symptom severity; rather, hostility is a strong determinant of coronary attack among hypertensive men with IHD.

Alcohol-induced changes in serum lipoproteins and in their metabolism.

The effects of alcohol intake on serum lipids and lipoproteins depend on the dose and mode of alcohol intake, individual susceptibility, genetic variables, and dietary factors. Therefore the changes of lipoprotein pattern are different among moderate and heavy drinkers. Moderate intake of alcohol increases the concentrations of apolipoproteins (apo) AI, apo AII, and high-density lipoprotein subfraction (HDL3) in plasma without any effects on other lipoproteins. If alcohol intake exceeds 60 to 80 gm per day, the synthesis of very low-density lipoprotein (VLDL) particles is stimulated. Even short-term use of alcohol stimulates lipoprotein lipase (LPL) activity in adipose tissue, and consequently the concentration of VLDL in plasma stays normal or is even subnormal. If alcohol intake continues in excessive amounts, the increased transport rate of VLDL particles as a result of high LPL activity results in the up regulation of HDL2. This is clearly evident in chronic alcoholics. Low or subnormal low-density lipoprotein (LDL) levels are another characteristic of the lipoprotein pattern in chronic alcoholics. The increase of HDL (HDL2) and reduction of LDL levels could well explain the reduced risk of coronary heart disease in chronic alcoholics, whereas the causal factors remain open among moderate drinkers.

Alcohol-related diseases associated with ischaemic heart disease: a three-year follow-up of middle-aged male hospital patients.

Mortality and morbidity from ischaemic heart disease (IHD) was studied in 5404 Finnish males aged 35-64 years who had been hospitalised for alcohol-related disease in 1972 without any admissions for IHD during that same period. By record-linkage, morbidity and mortality were followed up to the end of 1975. The mortality of patients with alcohol-related diseases was compared to 1120 patients with acute appendicitis by calculating indirectly age-standardised mortality ratios (SMR). The mortality and morbidity of 5963 patients with acute myocardial infarction or angina pectoris was also studied. The following SMRs for IHD mortality, non-fatal-IHD-hospitalisation and for mortality from all causes respectively, were found: acute myocardial infarction 11.6, 7.2 and 7.2; alcohol intoxication 6.0, 4.5 and 4.5; angina pectoris 5.2, 10.5 and 3.4; liver cirrhosis 2.2, 2.5 and 11.8; alcoholism 1.9, 1.9 and 3.6; pancreatitis 1.8, 1.2 and 4.4; alcohol psychosis 1.7, 2.5 and 4.2. IHD mortality and morbidity appeared to be more prevalent in patients hospitalised with alcohol intoxication than in patients with other alcohol-related diseases. This suggests that rapid drinking predisposes both to serious intoxication and to fatal disturbances of cardiac rhythm.

Nonenzymatic glucosylation of homologous low density lipoprotein and albumin renders them immunogenic in the guinea pig.

Nonenzymatic glucosylation of low density lipoprotein (LDL) and other plasma and structural proteins is enhanced in diabetics. Because conjugated carbohydrates are known to play an important role in the immunogenicity of proteins, we sought to determine if glucosylation of LDL (yielding Glc-LDL) and albumin would make them immunogenic. Therefore, we immunized guinea pigs with homologous glucosylated proteins and measured antibody response by solid-phase radioimmunoassay. Glucosylation of LDL in the presence of cyanoborohydride yields glucitol-lysine as the glucose adduct. Immunization with this Glc-LDL yielded a high-titered antiserum that reacted specifically with guinea pig Glc-LDL but not native LDL. Glucitol-lysine was an effective competitor for binding to the antibody, as were other reductively glucosylated human proteins. Glucosylation of LDL by incubation with glucose in the absence of a reducing agent yields fructosyllysine as the glucose adduct. This product, which has been demonstrated in human plasma, was also immunogenic, though the antiserum produced was of lower titer and affinity. Homologous glucosylated albumin was also immunogenic. These data suggest that nonenzymatic glucosylation of proteins could lead to autoantibody production and the formation of immune complexes in diabetic plasma and tissues.