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Recent clinical and experimental studies have suggested that antioxidant supplements might actually have harmful as well as beneficial effects in the setting of cardiovascular disease. The mechanisms underlying the beneficial effects of the various antioxidants are poorly understood in humans. Reperfusion-associated myocardial injury, and particularly the phenomenon of stunning, is important because it occurs in clinical settings and may condition the prognosis after short ischemic insult. We studied the effects of chronic (3 months) alpha-tocopherol supplementation with a large oral dose (500 mg daily) on myocardial contractility (stunning) and ventricular arrhythmias in a dog model of short ischemia followed by reperfusion. Twenty dogs were randomized to either an alpha-tocopherol supplemented or a control group. After 3 months, dogs were anesthetized and underwent a 20-min coronary artery occlusion followed by reperfusion. Myocardial regional blood flow was measured by the radioactive microsphere technique and myocardial contractility by sonomicrometry. Plasma alpha-tocopherol was measured by high-performance liquid chromatography in all dogs. Twelve dogs (seven supplemented and five controls) developed ventricular fibrillation at reperfusion, showing no difference between groups. Hemodynamic parameters, blood flow in the ischemic area (collateral flow), and area at risk were similar in the two groups. Regional systolic segment shortening in the ischemic area was similar during ischemia and reperfusion in both groups, representing 41 +/- 15% (mean +/- SEM) of baseline contractility in controls and 51 +/- 8% in supplemented dogs after 150 min of reperfusion. Plasma alpha-tocopherol level was higher in supplemented than in controls (19.1 +/- 1.6 and 6.9 +/- 0.6 mg/L; p < 0.001). Thus a long-term large dose of alpha-tocopherol had no significant effect on postischaemic ventricular arrhythmias and dysfunction (myocardial stunning) in this canine model. These data suggest that if alpha-tocopherol supplementation might be useful to improve the prognosis of coronary patients, it is likely not by interfering with the stunning phenomenon.
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PMID:Effect of chronic oral supplementation with alpha-tocopherol on myocardial stunning in the dog. 915 54

We assessed the effect of a diet high in leafy and green vegetables, fruit, and nuts on serum lipid risk factors for cardiovascular disease. Ten healthy volunteers (seven men and three women aged 33 +/- 4 years [mean +/- SEM]; body mass index, 23 +/- 1 kg/m2) consumed their habitual diet (control diet, 29% +/- 2% fat calories) and a diet consisting largely of leafy and other low-calorie vegetables, fruit, and nuts (vegetable diet, 25% +/- 3% fat calories) for two 2-week periods in a randomized crossover design. After 2 weeks on the vegetable diet, lipid risk factors for cardiovascular disease were significantly reduced by comparison with the control diet (low-density lipoprotein [LDL] cholesterol, 33% +/- 4%, P < .001; ratio of total to high-density lipoprotein [HDL] cholesterol, 21% +/- 4%, P < .001; apolipoprotein [apo] B:A-I, 23% +/- 2%, P < .001; and lipoprotein (a) [Lp(a)], 24% +/- 9%, P = .031). The reduction in apo B was related to increased intakes of soluble fiber (r = .84, P = .003) and vegetable protein (r = -.65, P = .041). On the vegetable compared with the control diet, the reduction in total serum cholesterol was 34% to 49% greater than would be predicted by differences in dietary fat and cholesterol. A diet consisting largely of low-calorie vegetables and fruit and nuts markedly reduced lipid risk factors for cardiovascular disease. Several aspects of such diets, which may have been consumed early in human evolution, have implications for cardiovascular disease prevention.
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PMID:Effect of a diet high in vegetables, fruit, and nuts on serum lipids. 916 Aug 20

We have used an oesophageal Doppler to measure aortic blood flow velocity before, during and after induction of carbon dioxide pneumoperitoneum in 10 consecutive patients, mean age 58 yr, undergoing laparoscopic hernia repair. Derived values for stroke distance, minute distance and systemic vascular resistance showed considerable interpatient variation indicating unpredictable haemodynamic responses. Five minutes after insufflation of the abdomen there was a significant increase in mean arterial pressure from 82.5 to 103.6 mm Hg (P < 0.05) but both stroke distance and minute distance decreased significantly (mean 12.0 (SEM 1.4) cm to 9.0 (0.7) cm, P < 0.05; and 747.5 (82) cm min-1 to 596 (49) cm min-1, P < 0.05; respectively) indicating a significant decrease in cardiac output. There was a corresponding increase in the index of systemic vascular resistance from 1092 (747) to 2079 (400) (P < 0.05) which persisted after deflation of the abdomen. Oesophageal Doppler can provide continuous online haemodynamic data with a rapid response to acute changes and may have a role in non-invasive haemodynamic monitoring during laparoscopic procedures in older patients with cardiovascular disease.
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PMID:Assessment of cardiovascular changes during laparoscopic hernia repair using oesophageal Doppler. 917 64

Endothelial dysfunction is a prevalent phenomenon in non-insulin dependent diabetic (NIDDM) patients with hypertension and albuminuria, and may contribute to the development and progression of cardiovascular disease, which is the main cause of the high morbidity and mortality observed in these patients. Therefore the aim of our study was to evaluate whether inhibition of angiotensin-converting enzyme (with lisinopril 10-20 mg day-1) could ameliorate endothelial dysfunction more than reducing blood pressure with conventional antihypertensive treatment (atenolol 50-100 mg day-1), usually in combination with a diuretic. We performed a 12-month prospective, randomized, double-blind, parallel study in 43 hypertensive NIDDM patients with diabetic nephropathy (21 treated with lisinopril and 22 with atenolol). The following variables were measured: 24-h ambulatory blood pressure (ABP); transcapillary escape rate of albumin (TERalb; i.e. initial disappearance of intravenously injected 125I-labelled human serum albumin); serum concentrations of von Willebrand factor (vWF), using ELISA, and urinary albumin excretion rate (UAE). Data are presented for 32 patients (16 lisinopril and 16 atenolol; age 60 years, SD 8; 25 males) out of 35 who completed the study and had valid measurements of TERalb. At baseline the two groups were comparable; TERalb (8.5 (SEM 0.6) vs. 7.2 (0.4)%); vWF (2.09 (range 0.82-4.34) vs. 1.97 (0.95-3.86) IU ml-1; UAE 916 (x/divided by antilog SEM 1.3) vs. 1444 (1.2), and mean ABP 110 (SEM 3) vs. 113 (2) mmHg, in the lisinopril and atenolol group, respectively. During follow up, the mean ABP was equally reduced in the lisinopril and atenolol group, by 12 (SEM 2) vs. 10 (2) mmHg, respectively, TERalb decreased in the lisinopril group by 0.6 (SEM 0.7)%, whereas it increased in the atenolol group 1.5 (0.5)%; the mean difference was 2.2% (95% CI, 0.5 to 3.9; p = 0.015). UAE was reduced by 45% (95% CI, 25 to 60) in the lisinopril group vs. 10% (-15 to 30) in the atenolol group (p = 0.014). Serum vWF was not changed during follow up in either group. Our study suggests that lisinopril has both reno- and vasculoprotective properties in hypertensive NIDDM patients with diabetic nephropathy.
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PMID:Lisinopril improves endothelial dysfunction in hypertensive NIDDM subjects with diabetic nephropathy. 927 69

High plasma plasminogen activator inhibitor-1 (PAI-1) activity is a frequent finding in obesity, and both PAI-1 and obesity are risk factors for cardiovascular disease. To study the mechanisms underlying increased PAI-1 levels in obese individuals, gene expression and secretion of PAI-1 were measured in human abdominal subcutaneous adipose tissue. A total of 32 obese, otherwise healthy subjects and 10 never-obese healthy subjects with a body mass index (BMI) of 42.6 +/- 1.2 and 24.3 +/- 1.9 kg/m2 (mean +/- SEM), respectively, were investigated. Plasma PAI-1 activity, adipose tissue PAI-1 secretion and adipocyte PAI-1 mRNA levels were increased seven-fold (p < 0.0001), sixfold (p < 0.0001) and twofold (p < 0.05), respectively, in the obese group. There were clear associations between adipose tissue secretion of PAI-1 and PAI-1 mRNA levels on the one hand and fat cell volume on the other (r = 0.68, p < 0.0001 and r = 0.51, p < 0.01, respectively, in the obese group). PAI-1 mRNA levels were also related to the amount of PAI-1 secreted among obese individuals (r = 0.31, p = 0.09). It is concluded that adipose tissue secretes significant amounts of PAI-1, that PAI-1 secretion from adipose tissue is increased in obesity, and that PAI-1 secretion is related to the lipid content and cell volume of fat cells. Plasma PAI-1 activity is elevated in obesity, at least in part due to increased gene expression in adipocytes, which, in turn, enhances PAI-1 secretion from adipose tissue.
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PMID:Adipose tissue secretion of plasminogen activator inhibitor-1 in non-obese and obese individuals. 949 32

Heart-rate reduction is an important element of patient management during cardiac bypass surgery and in therapeutic measures for combating ischemia and relieving pain in patients with angina. UL-FS 49 is a novel bradycardic agent that purportedly acts solely on the sinoatrial node without potentially deleterious effects on arterial pressure and cardiac inotropism. However, little is known about influences of this agent on neuronal tissue and cardiovascular reflexes. Moreover, left ventricular hypertrophy, which often accompanies cardiovascular disease, is known to attenuate the arterial baroreflex and could have effects interactive with those of UL-FS 49. In this study, the effects of UL-FS 49 on the arterial baroreflex were tested in normal rats (N), rats with left ventricular hypertrophy 14 days after abdominal aortic constriction (AC), and sham-operated controls (SH). Arterial baroreflex sensitivity (BRS) was estimated as the slope of the relation between mean arterial pressure (independent variable) and the RR interval (dependent variable). At the time of study, the AC group had significantly greater mean arterial pressure than either SH or N (159 +/- 2, 122 +/- 3, and 124 +/- 3 mm Hg, respectively; mean +/- SEM, p < 0.01) and significantly greater left ventricular mass to body mass ratio than did SH (3.73 +/- 0.11, 2.33 +/- 0.11 mg/g; p < 0.01). As expected, BRS was significantly depressed in AC, compared with either SH or N (0.52 +/- 0.16, 1.48 +/- 0.12, 1.69 +/- 0.25 ms/mm Hg, respectively; p < 0.01). Despite its potent dose-dependent bradycardic effects in all three groups, UL-FS 49 did not affect BRS significantly in any group. These results show that the arterial baroreflex is largely unaffected by UL-FS 49 in both normal rats and rats with systemic hypertension and left ventricular hypertrophy.
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PMID:UL-FS 49 (zatebradine) does not affect arterial baroreflex in conscious normal or aortic-constricted rats. 955 94

The molecular variants M235T and T174M of the angiotensinogen gene have been linked to essential hypertension in some populations, but there are discrepancies about this association in other studies. We studied 75 patients with essential hypertension (BP > 160/100 mm Hg) from our outpatient clinic, aged 55+/-1 years, 30 men, systolic BP 182+/-2.5, diastolic BP 109+/-1 mm Hg (mean +/- SEM), and a family history of the disease. Target organ damage was evaluated by measuring urinary albumin excretion rate, left ventricular hypertrophy, and fundoscopy. As a control group, 75 healthy subjects with BP < 130/85 mm Hg and with no family history of cardiovascular disease were selected. M235T and T174M angiotensinogen genotypes were determined by PCR and subsequent digestion of the products with SfaNI and NcoI, respectively. The frequency (q) of genotypes of the variant M235T in the patients with essential hypertension was MM 0.31, MT 0.41, and TT 0.28, not significantly different (P = .93) from that of the controls (MM 0.28, MT 0.44, and TT 0.28). For the variant T174M, the genotype frequencies in hypertensives were TT 0.83, TM 0.15, and MM 0.02, which was not significantly different (P = .89) from that of the controls (TT 0.86, TM 0.12, and MM 0.02). Similarly, there was no evidence for association between angiotensinogen genotypes and hypertension in subjects aged < or = 40 years old (n = 24) or with severe (stage III) hypertension (n = 31). Within the group of patients with essential hypertension, there were no differences in genotype distribution between patients with and without retinopathy (n = 31), left ventricular hypertrophy (n = 37), or microalbuminuria (n = 14). This study shows that M235T and T174M variants are not associated either with essential hypertension or with target organ damage in a Spanish sample.
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PMID:Angiotensinogen gene M235T and T174M polymorphisms in essential hypertension: relation with target organ damage. 960 82

The influence of progestogens in combination with 17beta-estradiol (E2) on cardiovascular disease remains controversial. This study investigated the effect of norethindrone acetate (NETA) combined with E2 on aortic atherosclerosis. Eighty mature female rabbits were ovariectomized, then fed a cholesterol-rich diet (240 mg/d) for 14 weeks to induce aortic atherosclerosis. They were randomized to four equally large groups for the following 38-week intervention period. One group received placebo, another group oral E2 4 mg daily (E2), and the last two groups oral E2 4 mg daily combined with either NETA 1 mg (E2NETA1) or NETA 3 mg (E2NETA3). The cholesterol intake was reduced to a "maintenance" level of 80 mg/d during the intervention period. Total serum cholesterol and ultracentrifuged lipoproteins were analyzed enzymatically throughout the study. The cholesterol content in the aortic wall was 2.76+/-0.44 micromol/cm2 (mean+/-SEM) in the E2NETA1 group, 1.77+/-0.37 micromol/cm2 in the E2NETA3 group, 5.46+/-0.77 micromol/cm2 in the E2 group, and 7.20+/-0.94 micromol/cm2 in the placebo group (ANOVA P<0.0001). The difference (in the aortic cholesterol accumulation) between the E2 and each of the combined E2/NETA groups was statistically significant (P<0.01) but could only partly be explained by the differences in serum lipids and lipoproteins. In conclusion, NETA enhances the antiatherogenic effect of E2 in cholesterol-fed rabbits. This effect is only partially mediated through changes in serum lipids and lipoproteins.
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PMID:Norethindrone acetate enhances the antiatherogenic effect of 17beta-estradiol: a secondary prevention study of aortic atherosclerosis in ovariectomized cholesterol-fed rabbits. 963 29

Resistance to insulin-mediated glucose disposal has been postulated to predispose individuals to a cluster of associated abnormalities (Syndrome X) known to increase risk of cardiovascular disease (CVD). Although several abnormalities subsumed under the rubric of Syndrome X have been shown to predict CVD, there has been no prospective study evaluating the power of insulin resistance, the putative fundamental defect in the syndrome, in this context. Therefore, this study was initiated to evaluate the hypothesis that resistance to insulin-mediated glucose disposal would predict the development of CVD in healthy volunteers. To accomplish this goal, 147 normal, healthy, nonobese, volunteers were evaluated [4.7 +/- 0.1 yr (mean +/- SEM)] after baseline measurements of steady state plasma glucose concentration (an estimate of insulin-mediated glucose disposal), as well as other CVD risk factors. Clinical end points developed in 13 subjects during the follow-up period; hypertension in 5, coronary artery disease in 4, cerebrovascular accident in 3, and peripheral vascular disease in 1. There was a significant univariate relationship between SSPG and CVD (P < 0.002), with the majority of the events taking place in the tertile of subjects with the highest SSPG concentration, i.e. the greatest degree of insulin resistance. In contrast, no CVD events were observed in the tertile with the lowest SSPG concentrations; the most insulin sensitive. SSPG was also related significantly to diastolic blood pressure, triglyceride, and low-density lipoprotein and high-density lipoprotein cholesterol concentrations, and the glucose and insulin responses to oral glucose. All of these relationships were independent of age, gender, body mass index, estimates of physical activity, and smoking history. When SSPG was paired with each of the other variables in a series of multiple regression models, only SSPG, or insulin response, were independent predictors of CVD events. In conclusion, approximately one of every five healthy, nonobese subjects in the most insulin-resistant tertile, followed for approximately 5 yr, had a serious clinical event. These data highlight the importance of insulin resistance as a predictor of CVD.
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PMID:Resistance to insulin-mediated glucose disposal as a predictor of cardiovascular disease. 970 45

Obesity is a major factor contributing to hypertension and increased risk of cardiovascular disease. Regular consumption of dietary fish and omega3 fatty acids of marine origin can lower blood pressure (BP) levels and reduce cardiovascular risk. This study examined the potential effects of combining dietary fish rich in omega3 fatty acids with a weight loss regimen in overweight hypertensive subjects, with ambulatory BP levels as the primary end point. Using a factorial design, 69 overweight medication-treated hypertensives were randomized to a daily fish meal (3.65 g omega3 fatty acids), weight reduction, the 2 regimens combined, or a control regimen for 16 weeks. Sixty-three subjects with a mean+/-SEM body mass index of 31.6+/-0.5 kg/m2 completed the study. Weight fell by 5.6+/-0.8 kg with energy restriction. Dietary fish and weight loss had significant independent and additive effects on 24-hour ambulatory BP. Effects were greatest on awake systolic and diastolic BP (P<0.01); relative to control, awake pressures fell 6.0/3.0 mm Hg with dietary fish alone, 5.5/2.2 mm Hg with weight reduction alone, and 13.0/9.3 mm Hg with fish and weight loss combined. These results also remained significant after further adjustment for changes in urinary sodium, potassium, or the sodium/potassium ratio, as well as dietary macronutrients. Dietary fish also significantly reduced 24-hour (-3.1+/-1.4 bpm, P=0.036) and awake (-4.2+/-1.6 bpm, P=0. 013) ambulatory heart rates. Weight reduction had a significant effect on sleeping heart rate only (-3.2+/-1.7 bpm, P=0.037). Combining a daily fish meal with a weight-reducing regimen led to additive effects on ambulatory BP and decreased heart rate. The effects were large, suggesting that cardiovascular risk and antihypertensive drug requirements are likely to be reduced substantially by combining dietary fish meals rich in omega3 fatty acids with weight-loss regimens in overweight medication-treated hypertensives. The reduction in heart rate seen with dietary fish suggests a cardiac/autonomic component, as well as vascular effects, of increased consumption of omega3 fatty acid from fish.
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PMID:Effects of dietary fish and weight reduction on ambulatory blood pressure in overweight hypertensives. 977 68


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