Circulating oxidized low-density lipoprotein and common carotid artery intima-media thickness in a random sample of middle-aged men.

Circulating oxidized low-density lipoprotein (oxLDL) has been suggested to play an important role in atherosclerosis development. According to previous observations, oxLDL correlates with clinically manifest coronary and carotid artery disease. We investigated the association between the oxLDL concentration measured directly in plasma and common carotid artery intima-media thickness (IMT) in a population-based, case-control study in middle-aged men from Southern Finland. oxLDL was determined in 214 men by a commercially available sandwich ELISA test (Mercodia). Carotid artery IMT was measured at 12 standardized segments by B-mode ultrasonography (at the near and far wall of the left and right common carotid arteries, bifurcations and internal carotid arteries), and the overall mean maximum IMT (MMaxIMT) was calculated. The MMaxIMT of the carotid arteries was significantly associated with circulating oxLDL (r(s) = 0.16, p = 0.018). In a stepwise multiple regression model with MMaxIMT as dependent variable and systolic blood pressure, smoking, oxLDL, HDL cholesterol and apolipoprotein B as covariates, systolic blood pressure (beta = 0.22, p < 0.001), oxLDL (beta = 0.15, p = 0.022) and smoking (beta = 0.17, p = 0.014) showed an independent association with IMT (R(2) = 0.10, p < 0.001). Our results show that oxLDL measured directly from plasma is independently associated with subclinical carotid artery atherosclerosis in middle-aged men.

Relationship between high-density lipoprotein paraoxonase gene M/L55 polymorphism and carotid atherosclerosis differs in smoking and nonsmoking men.

The enzyme paraoxonase (PON) can eliminate lipid peroxides and is believed to protect against low-density lipoprotein oxidation. A common polymorphism in the PON gene (PON1) causes an amino acid substitution of methionine (M) for leucine (L) at position 55 in the protein, which changes the activity of PON and can affect the risk of atherosclerosis. Because smoking is associated with increased lipid peroxidation, we studied the relationship between PON M/L55 polymorphism and the carotid artery intima-media thickness (IMT) in smokers or previous smokers (n = 112) and nonsmokers (n = 87). IMT was measured at 3 standardized segments by B-mode ultrasonography, and the overall mean IMT value of 199 randomly selected men (mean age 54.2 +/- 3.0 years) was calculated. Subjects with IMT > 1.7 mm in at least 1 standard site were considered to have carotid artery atherosclerotic disease (CAAD). For analysis, L55 homozygotes were compared with the M55 allele carriers. Nonsmoking L55 homozygotes had an 8.9% (95% confidence interval [CI], 1.6 to 16.8) higher overall mean IMT than M55 allele carriers. In smokers, however, the M55 allele carriers tended to have higher overall mean IMT values than L55 homozygotes. There was also a statistically significant interaction between M/L55 genotype and smoking status on CAAD (P =.009) by logistic regression analysis. Among nonsmokers, the L55 homozygotes had an odds ratio of 4.22 (95% CI, 1.06 to 16.8) for CAAD compared with nonsmoking M55 allele carriers. Contrary to nonsmokers, the smoking M55 allele carriers had an odds ratio of 2.22 (95% CI, 0.82 to 6.01) for CAAD when the L55/L55 genotype of smokers was a reference group. These data suggest that in nonsmoking men, a PON L55/L55 genotype may represent a genetic risk factor for CAAD. The reverse effect in smokers implies that the ability of PON to protect against CAAD is influenced by cigarette smoking. The efficiency of this inhibition probably depends on the PON M/L55 genotype.

Apolipoprotein E polymorphism and carotid artery intima-media thickness in a random sample of middle-aged men.

Genetic polymorphism of apolipoprotein E (apoE) is an important factor in the development of coronary artery disease but the results concerning apoE genotype and carotid artery atherosclerosis remain controversial. We investigated a random sample of 189 Finnish middle aged men (mean age 54 years, range 50-59) to assess the role of apoE in the process of carotid atherosclerosis. Intima-media thickness (IMT) of the carotid artery wall was measured at three standardised segments (common carotid artery, bifurcation and internal carotid artery) by B-mode ultrasonography. Overall mean IMT value was also calculated. The carriers of E3/2 (n=20) genotype had significantly lower (P<0.01) total cholesterol and LDL cholesterol concentrations than carriers of E3/3 genotype (n=109) or the E4 allele (n=60). ApoE polymorphism was associated with common carotid artery IMT (P=0.034) when adjusted for age and body-mass index (model 1). The carriers of E3/2 had on average 9% (95% CI 0.8-16%, P=0.028) lower common carotid IMT values than the carriers of E3/3. After further adjustment with LDL and HDL cholesterol, systolic blood pressure, lipoprotein (a), apolipoprotein B and pack-years of smoking (model 2) the association was not statistically significant. The overall mean IMT varied significantly with apoE genotype (P=0.03 for model 1 and P=0.07 for model 2), and it was also lowest in the carriers of E3/2 genotype. This suggests that apoE E3/2 genotype is a protective factor in the development of carotid artery atherosclerosis in randomly selected middle-aged men. The favourable effect might be mediated at least partly by the lowering effect of E3/2 genotype on serum cholesterol.

Controlled 5-mo aerobic training improves heart rate but not heart rate variability or baroreflex sensitivity.

Endurance-trained athletes have increased heart rate variability (HRV), but it is not known whether exercise training improves the HRV and baroreflex sensitivity (BRS) in sedentary persons. We compared the effects of low- and high-intensity endurance training on resting heart rate, HRV, and BRS. The maximal oxygen uptake and endurance time increased significantly in the high-intensity group compared with the control group. Heart rate did not change significantly in the low-intensity group but decreased significantly in the high-intensity group (-6 beats/min, 95% confidence interval; -10 to -1 beats/min, exercise vs. control). No significant changes occurred in either the time or frequency domain measures of HRV or BRS in either of the exercise groups. Exercise training was not able to modify the cardiac vagal outflow in sedentary, middle-aged persons.

Comparison of bicycle, heavy isometric, dipyridamole-atropine and dobutamine stress echocardiography for diagnosis of myocardial ischemia.

Several stress echocardiography (SE) modalities have been introduced for diagnosing coronary artery disease (CAD). Exercise and dobutamine SE are considered to have better diagnostic accuracy than vasodilator or isometric SE, but there are no studies in a single group of patients comparing these 3 tests with heavy 2-arm isometric SE. The purpose of this study was to determine the diagnostic characteristics of 4 SE methods in patients with chest pain. Altogether, 60 patients (age +/- SD 55.1 +/- 2.1 years) were tested with bicycle, heavy 2-arm isometric, dipyridamole-atropine and dobutamine SE. CAD (>50% stenosis) was present in 44 patients; 26 patients had 1-vessel disease. During bicycle SE, the double product at peak stress was higher than during dobutamine and dipyridamole-atropine SE (26.5 x 10(3), p <0.005 vs dobutamine and dipyridamole-atropine SE), and peak wall motion score index (1.40) was higher than during dipyridamole-atropine and isometric SE (1.26 and 1.07, respectively, p <0.05 vs bicycle SE). Bicycle, dipyridamole-atropine, and dobutamine SE had higher sensitivity than isometric SE (90%, 93%, 95%, and 30%, respectively, p <0.05 isometric SE vs others). There were no statistically significant differences with regard to specificity. Similarly, bicycle, dipyridamole-atropine, and dobutamine SE had a higher diagnostic accuracy than isometric SE (78%, 88%, 87% and 47%, respectively, p <0.05 isometric SE vs others). We conclude that bicycle, dipyridamole-atropine, and dobutamine SE have an equal diagnostic accuracy in detecting CAD despite higher double product and ischemic burden at peak stress during bicycle and dobutamine SE over dipyridamole-atropine SE. Heavy isometric SE is inaccurate.

Accuracy of a novel real-time microprocessor QRS detector for heart rate variability assessment.

Assessment of heart rate variability from 24-h recordings requires a high-quality Holter, expensive equipment and multistage processing of recordings. We compared a new personal computer-based digital QRS detector system with a Holter recorder, and found the two methods to be equally accurate in time and frequency domain measures of heart rate variability.

Relationship of angiotensin-converting enzyme gene polymorphism to carotid wall thickness in middle-aged men.

The insertion/deletion (I/D) polymorphism of the human angiotensin-converting enzyme (ACE) gene is a major determinant of circulating ACE levels. The D allele has been suggested to be a potent risk factor for coronary artery disease; however, the effect of the ACE gene on carotid atherosclerosis remains controversial. We therefore studied the relationship between the ACE gene I/D polymorphism and carotid artery intima-media thickness (IMT). A random sample of 300 men aged 50-59 years living in southern Finland were selected, and 233 agreed to participate (74%). Data were collected in 219 subjects. Quantitative B-mode ultrasonography was used to measure the maximum near and far wall IMT of right and left common, bifurcation, and internal carotid artery. The mean maximum IMT (overall mean) was calculated as the mean of 12 maximum IMTs at 12 standard sites. Patients with an IMT higher than 1.7 mm in at least one of 12 standard sites were assumed to have carotid atherosclerosis. The I/D polymorphism was determined by polymerase chain reaction. Overestimation of the frequency of the DD genotype was eliminated by insertion-specific primer and the inclusion of 5% dimethylsulfoxide. No significant differences were found in carotid wall thickness between the three genotypes; the overall mean IMT were 1.18 +/- 0.30, 1.22 +/- 0.24, and 1.08 +/- 0.40 mm in genotypes of II, ID, and DD, respectively. Similarly, the ACE genotypes and allele frequencies did not differ significantly between the subjects with and those without carotid atherosclerosis. There was no association in the subgroups among only nonsmoking subjects or subjects without chronic medication. The present data indicate that the I/D polymorphism of the ACE gene is not related to carotid IMT and is unlikely to play a major role in carotid atherosclerosis.

Variation of ambulatory blood pressure in healthy middle-aged men.

The majority of the reference data on ambulatory blood pressure (ABP) monitoring is based on fixed, predefined times for waking hours and sleep. Our aim was to determine the level of ABP according to diary entries when awake, at work, at home and during sleep in a sample of normotensive, middle-aged men. The dipping-status was also determined. All measurements were taken with a non-invasive auscultatory device on a normal working day. A total of 62 clinically healthy, normotensive men without a history of elevated BP were included. The mean resting BP of the group was 122/73 mm Hg. The 24-h systolic BP (SBP) was 114.4 +/- 8.6 mm Hg (95% CI 112.3, 116.6), while the diastolic BP (DBP) was 80.4 +/- 7.2 mm Hg (95% CI 78.5, 82.2). SBP when awake was 120.5 +/- 9.4 mm Hg (95% CI 118.1, 122.9) and diastolic pressure 84.4 +/- 7.7 mm Hg (95% CI 82.5, 86.4). The corresponding values for systolic and diastolic pressures during sleep were 101.2 +/- 8.5 mm Hg (95% CI 99.1, 103.4) and 71.7 +/- 7.7 mm Hg (95% CI 69.7, 73.6). The difference between day and night was 19.2 +/- 7.0 mm Hg for systolic and 12.7 +/- 6.0 mm Hg for diastolic pressure. The number of men whose systolic and diastolic pressure dropped less than 10% while asleep (non-dippers) was eight (13%) and 15 (24%), respectively. If the mean +/- 2 standard deviation interval is considered, the range of normality averaged 102-139/69-100 mm Hg when awake, 84-118/56-87 mm Hg when asleep and 97-132/66-95 over 24 h. The awake-sleep pressure difference did not correlate with the 24-h average.