The regular consumption of a polyphenol-rich apple does not influence endothelial function: a randomised double-blind trial in hypercholesterolemic adults.

BACKGROUND/OBJECTIVES: Epidemiological studies suggest that apple consumption is associated with a reduction in cardiovascular disease risk. Apple polyphenols may contribute to explain these effects. Endothelial dysfunction has been associated with early stage of atherosclerosis and polyphenols from various dietary sources have been shown to reverse it. The aim of the present study was to investigate the effect of the consumption of a polyphenol-rich apple on endothelial function. SUBJECTS/METHODS: In all, 30 hypercholesterolemic volunteers were included in a double-blind, randomized crossover trial. They successively consumed 40 g of two lyophilized apples, polyphenol-rich and polyphenol-poor, providing respectively 1.43 and 0.21 g polyphenols per day during two 4-week periods separated by a 4-week washout period. RESULTS: Brachial artery flow-mediated vasodilation (FMD) was assessed at the beginning and at the end of each intervention period. FMD did not differ between the polyphenol-rich and the polyphenol-poor apples, neither did the other cardiovascular disease risk factors (plasma lipids, homocysteine, antioxidant capacity). CONCLUSIONS: These data suggest that over a 4-week period, the consumption of a polyphenol-rich apple does not improve vascular function in hypercholesterolemic patients.

Subclinical atherosclerosis modeling: Integration of coronary artery calcium score to Framingham equation.

Medical prevention consists to identify as soon as possible apparently healthy individuals who develop a disease and to engage them for active preventive treatment. Several cross-sectional studies of general populations or high cardiovascular risk have shown that coronary calcium score (coronary artery calcium, CAC) was positively associated with traditional risk factors (hypertension, dyslipidemia, diabetes, and smoking) and some new risk factors (fibrinogen). In this work, we first calculated, among 618 men, the risk of 10-years cardiovascular heart disease (CHD) according to the Framingham risk model, and then we calculated the probability that the CAC score of an individual falls in all four CAC categories (0, 1-100, 101-400 and > 400). We obtained risk factors adjusted relative risk (RR) estimates from a meta-analysis comparing the risk of coronary heart disease in individuals with CAC scores of 1-100 (RR = 1.7), 101 - 400 (RR = 3.0) and > 400 (RR = 4.3) with the risk of a person with a CAC score zero. The new model for the risk of CHD for each CAC score category were then calculated assuming an average 1-year risk of CHD and risk assessment of the four CAC score categories, weighted by the probability that scores fall into each category. The combination of modeling the CCA with the modeling of conventional risk factors allows obtaining a remarkable predictive value that can improve the assessment of overall risk Framingham through the reclassification of the risk of CHD to an extent which may be clinically important.

Do arterial effects of antihypertensive drugs depend on subject's serum cholesterol?

Effects of antihypertensive treatment on large arteries may be influenced by the type of drug and concomitant risk factors such as blood cholesterol. To explore these possibilities we investigated the common carotid artery of 20 subjects with low cholesterol and 19 subjects with high cholesterol, all with essential hypertension, randomly allocated to 3 months of treatment with nitrendipine (20 mg/d) or trandolapril (2 mg/d). Carotid parameters were determined by recording instantaneous pressure (applanation tonometry) and diameter (echotracking device) and by modeling the pressure-diameter loop to obtain the Peterson modulus, stiffness index, measured and isobaric compliances, and wall viscosity. Effects of drugs on carotid parameters did not differ, except on systolic and diastolic diameters (p < 0.01), which increased insignificantly under nitrendipine but decreased (p < 0.01) under trandolapril. Blood cholesterol status did not influence carotid effects of trandolapril, whereas patients with low and high cholesterol treated with nitrendipine exhibited significant differences in drug effects on (a) systolic and pulse pressures (p < 0.05), which decreased in patients with low cholesterol (p < 0.01, p < 0.05) but not in those with high cholesterol; (b) diastolic diameter (p = 0.05), which increased insignificantly in patients with low cholesterol but was unchanged in those with high cholesterol; and (c) wall viscosity (p < 0.01), which decreased in patients with low cholesterol (p < 0.05) but increased insignificantly in those with high cholesterol. Also, wall viscosity change under nitrendipine was positively related to the baseline blood cholesterol ( r = 0.64, p < 0.01). Thus, nitrendipine and trandolapril show noteworthy differences in their effects on the carotid artery, in particular with respect to the status of blood cholesterol, but these differences should be confirmed by larger studies.

A new DNA polymorphism in the 5' untranslated region of the human SREBP-1a is related to development of atherosclerosis in high cardiovascular risk population.

Sterol-regulatory element binding proteins (SREBPs) are ubiquitous transcription factors that regulate the genes encoding key proteins in the control of cholesterol homeostasis. We looked for mutations or polymorphisms within the sequences of the SREBP-1a gene critical for the synthesis and/or activity of the protein in 204 asymptomatic men. A single G deletion at base pair -36 of the translation initiation site (designated G-) was found using single-strand conformation polymorphism (SSCP), in addition to three rare variants. This new marker was then assessed for its influence on the lipid parameters of 812 men at high cardiovascular risk, and on the presence of echographic atherosclerotic plaque in their peripheral arteries. The allelic frequency of the -36delG polymorphism was 0.58. At least one plaque was found in the carotid in 24% of subjects, in the femoral arteries of 48%, and in the aorta of 25%. There were significant associations between the -36delG polymorphism and mean total cholesterol (p=0.02) and LDL-cholesterol (P=0.02). There was a graded relationship between the G- allele and the presence of carotid plaque (r=0.084, P=0.02). In addition, there was a statistically significant interaction between the -36delG genotype and the apoE phenotype for plasma LDL-cholesterol (P=0.04) and apoB (P=0.05), suggesting a gene-gene interaction. Stepwise multiple regression analysis for lipid traits, risk factors, and apoE phenotype showed an independent association between carotid plaque and the -36delG polymorphism (beta=0.311, P=0.03). Thus, we have identified a new polymorphism in the 5' untranslated region of the SREBP-1a gene, and demonstrated its association with an atherogenic lipid profile and echographic plaques.

[Homocystinuria in adulthood]. / L'homocystinurie à l'âge adulte.

Homocystinuria is a genetically determined inborn error of the methionine amino acid pathway characterized by increased plasma homocysteine. In its major form, homocystinuria, is due to cystathionine beta synthase deficiency. Treatment of these adulthood patients lead physicians to call up on the skilled advices of pediatricians. But prevention and treatment of age related vascular and osteoporotic complications are still to be evaluated.

Predictive value of waist-to-hip ratio on cardiovascular risk events.

BACKGROUND: A central distribution of adipose tissue is frequently associated with cardiovascular disease (CVD) and its risk factors. METHODS: Clinical usefulness of waist-to-hip ratio (WHR) for predicting the risk of cardiovascular events, estimated with models based on data from the Framingham and Prospective Cardiovascular Münster (PROCAM) studies was evaluated. SUBJECTS: These were 552 men and 160 women, asymptomatic and at risk for CVD, aged 30-74 y, recruited from an ongoing risk factor screening program conducted at worksites. RESULTS: Abdominal fatness was a strong predictor of cardiovascular complications in subjects whose WHR was in the top quintile (> 0.98 for men and > 0.91 for women). The estimated percentage rate of coronary heart disease (CHD, P <0.01) and death (P < 0.01), myocardial infarction (P < 0.01), stroke (P < 0.01), total CVD (P < 0.001) and death (P < 0.01) increased with increasing quintile of WHR in men and women. In the highest WHR, the number of subjects exceeding a 15% risk of developing a coronary event over the next 10 y was more than two-fold greater (odds ratio (OR) 2.60 (confidence intervals (CI) 1.09-6.54) than in the lowest WHR quintiles. Similar six-year myocardial infarction (MI) risks at each quintile of WHR were observed in men in both Framingham and PROCAM models. In the overall population, CHD estimates increased with increasing quintiles of WHR with the Framingham model and an adapted model for estimating probabilities of disease in the French population of the Prevention Cardiovasculaire en Médecine du Travail (PCV-METRA) group. CONCLUSION: Abdominal deposition of fat assessed by WHR may be of strong clinical value for predicting high risk of cardiovascular events.

Hippocrate: a safe robot arm for medical applications with force feedback.

We have developed a robotic system to assist doctors when they are moving ultrasonic probes on a patient's skin while exerting a given effort. The probes are used to monitor arteries for cardiovascular disease prevention, namely to reconstruct the three-dimensional profile of arteries. A preliminary feasibility study making use of an industrial robot has been made to validate the force control scheme. It has proven the interest of the robotized approach for such medical applications where force control is needed. In order to comply with safety constraints, a dedicated robotic system 'Hippocrate' has been designed. This paper describes the arm and the controller architectures, with emphasis on design strategies selected to meet safety requirements. Preliminary in vivo results are presented as well as a possible new application of Hippocrate as a tool for reconstructive surgery.

Charge heterogeneity of LDL in asymptomatic hypercholesterolemic men is related to lipid parameters and variations in the ApoB and CIII genes.

This study was carried out to examine the relationship between the charge on low density lipoproteins (LDLs) and lipid and clinical parameters in 104 asymptomatic dyslipidemic men and to identify biochemical and genetic factors that could contribute to the charge variability of LDL. LDL charge heterogeneity was evaluated by relative electrophoretic mobility (REM) on preformed 0.5% agarose gels and by chromatographic quantification of a minor electronegative LDL subfraction designated LDL(-). The mean REM value for LDL was 0.147+/-0.016 and the mean LDL(-) subfraction percentage was 5.6+/-2.8%. Both were positively correlated with common atherosclerotic risk factors, especially total cholesterol [for REM, r=0.27, P<0.005; for LDL(-), r=0.28, P=0.008] and LDL cholesterol [for REM, r=0.27, P=0.007; for LDL(-), r=0.26, P=0.01)] levels, and REM was positively correlated with triglycerides (r=0.27, P<0.005) and negatively with apoAI levels (r=-0.30, P<0.002). The variations in LDL charge were not due to oxidation, as measured by the lag phase and binding to the LDL receptor. The results of the 2 methods used to measure LDL charge were significantly correlated and had some identical characteristics (eg, association with LDL apoCIII content and plasma triglyceride levels in borderline and IIb dyslipidemic subjects); these methods reflect different specific features of LDL charge. The percentage of LDL(-) was correlated positively with the LDL sialic acid content (P<0.0001), whereas the REM was related to at least 2 distinct chromosomal loci. Multiple logistic analysis showed that individuals carrying minor alleles of BsrDI (P<0.05), apoCIII/SacI (P<0.01), as well as the frequent allele of XbaI (P<0.05) at the apoB and CIII gene loci had high REMs. This result suggests that LDL charge heterogeneity, which is positively correlated with the atherogenic lipid profile, is influenced by both genetic and biochemical factors.

Evidence of carotid artery wall hypertrophy in homozygous homocystinuria.

BACKGROUND: We aimed to determine whether intima-media thickness (IMT) was increased in the carotid artery of subjects with homocystinuria to better understand the in vivo contribution of homocysteine to early atherogenesis. METHODS AND RESULTS: We investigated ultrasonographically the right common carotid artery in 14 subjects with homozygous homocystinuria aged 3 to 34 years (mean, 13 years) and in 15 of their heterozygous parents aged 32 to 47 years (mean, 41 years) by comparison with 2 control groups of 15 healthy subjects of the same age. Far-wall IMT and lumen diameter were measured with a computerized program, and the cross-sectional area of the intima-media complex (CSA-IMC) was calculated from IMT and diameter. Comparison with their respective controls, adjusted for body surface area or height, showed that homozygotes had greater IMT (P<0.001) and CSA-IMC (P<0.05) and smaller diameter (P<0.05), whereas heterozygotes had values similar to their controls. Multivariate analysis of the arterial parameters with age, body surface area (or height), and plasma total homocysteine in the homozygous and heterozygous groups combined showed that IMT was related to age (P<0.05) and homocysteine (P<0.01), diameter was related to body surface area (P<0.001) or height (P<0.05), and CSA-IMC was related to age (P<0.05), body surface area (P<0.05) (but not height), and homocysteine (P<0.05). CONCLUSIONS: Homozygous homocystinuria was associated with common carotid wall hypertrophy, whereas heterozygous disease was not. Such hypertrophy may reflect a smooth muscle proliferation induced by hyperhomocysteinemia and represent a promising target for testing vascular effects of therapeutic measures to lower homocysteine.

Early atherosclerosis in human hypertension.

The detection of preclinical atherosclerosis may contribute to better identifying hypertensive subjects at high risk of complications. Three alterations can be diagnosed noninvasively: calcification, thickening, and stiffening of the arterial wall. Their prevalence is increased in asymptomatic hypertensives and their presence may have important prognostic significance, especially with respect to coronary artery disease. They are also ideal targets to test the efficacy of hypertensive therapy on the arterial wall. Finally, the detection of early atherosclerosis may help to improve the clinical management of hypertensive patients.

Preclinical changes of extracoronary arterial structures as indicators of coronary atherosclerosis in men.

BACKGROUND: Carotid artery structure change was associated with coronary artery stenosis by angiography of subjects who were for the most part symptomatic. OBJECTIVE: To determine whether structural changes at multiple extracoronary sites were associated with noninvasively detected coronary calcium for 94 asymptomatic high-risk men. METHODS AND RESULTS: B-mode ultrasonography allowed us to detect plaque at three sites (carotid, femoral, and abdominal aorta) and to measure intima-medial thickness both in common carotid and in femoral arteries. Ultrafast computed tomography determined the presence and amount of coronary calcification. After adjustment for age, plaques at two or three sites were associated with extensive amounts of coronary calcium [odds ratio 4.94 (95% confidence interval 1.08-23)], but not with the presence of coronary calcium; increase in carotid intima-medial thickness was not associated with presence and extent of coronary calcium; and increase in femoral intima-medial thickness was associated with presence of coronary calcium [odds ratio 1.44 (95% confidence interval 1.03-2)] and extensive coronary calcium [odds ratio 1.50 (95% confidence interval 0.97-2.33)]. Adjustment for cardiovascular risk factors attenuated these associations. CONCLUSIONS: Femoral intima-medial thickness predicted presence of coronary calcium whereas femoral intima-medial thickness and overall multiple plaques predicted extensive coronary calcium. Because coronary calcium is a marker of atherosclerosis and a predictor of coronary events, B-mode ultrasonography could be of clinical value for stratifying coronary risk.

Aortic stiffening does not predict coronary and extracoronary atherosclerosis in asymptomatic men at risk for cardiovascular disease.

Stiffness of aortic walls has been shown to be a marker of coronary and cerebrovascular diseases in patients with myocardial infarction or stroke. However, its value for predicting preclinical atherosclerosis has not been demonstrated. Therefore, this study tested the association of aortic wall stiffness and coronary and extracoronary atherosclerosis in the absence of clinical cardiovascular disease. In 190 asymptomatic men at cardiovascular risk, carotid-to-femoral pulse wave velocity (PWV) was measured mechanographically and the compliance of the aorta (C), as well as the intrinsic compliance (Ci), was deduced after correction for the effect of blood pressure. Also determined noninvasively were 1) the degree of coronary calcium deposit coded as grade 0, 1, 2, or 3 using ultrafast computed tomography; 2) the extent of extracoronary plaque detected by B-mode echography at three different sites (carotid, abdominal aorta, and femoral) coded as 0, 1, 2, or 3 diseased sites; and 3) the estimated Framingham coronary risk. The grade of coronary calcium was not associated with any aortic elastic parameter. The number of extracoronary diseased sites was not associated with PWV and C but correlated negatively with Ci before but not after age adjustment. The coronary risk correlated positively with PWV and negatively with C before but not after age adjustment and was not associated with Ci. In symptom-free subjects aortic stiffening does not predict the presence of coronary and extracoronary atheroma and therefore cannot be considered as a useful surrogate marker of early atherosclerosis.

Sex and topographic differences in associations between large-artery wall thickness and coronary risk profile in a French working cohort: the AXA Study.

Previous reports have investigated associations between carotid intima-media thickness (IMT) and cardiovascular risk factors. Our objective was to investigate this question in greater depth by measuring both femoral and carotid IMT in relation to sex and multifactorial coronary risk. We investigated carotid and femoral artery IMT by using ultrasonography in 326 men and 462 women, 17 to 65 years old. We also evaluated body mass index, blood pressure, blood lipids, glucose, smoking, and Framingham coronary risk. In both vessels, IMT was lower in women than in men. Significant relations between carotid and femoral IMT existed with age and most risk factors in both sexes. After adjustment for age, carotid IMT was related to risk factors in both sexes except for diastolic blood pressure, HDL cholesterol, and smoking in women, whereas femoral IMT was related to triglycerides and smoking in both sexes, systolic blood pressure and blood glucose in men, and total and HDL cholesterol in women. Significant unadjusted and age-adjusted relations of Framingham risk existed with carotid and femoral IMT in both sexes, but slopes of these relations were greater (1) before than after age adjustment, (2) in men than in women at both sites, except the femoral artery after age adjustment, and (3) at the carotid than at the femoral site in both sexes before age adjustment. Carotid IMT in men appears to be a more powerful predictor than it is in women and femoral IMT in both sexes in reflecting multifactorial coronary risk burden, but these differences are partly conditional on age.

Decreased regional blood flow in patients with acromegaly.

BACKGROUND AND AIMS: One-third of acromegalic patients have hypertension. Acromegaly is also associated with intrinsic cardiac abnormalities known collectively as a hyperkinetic heart syndrome, which is characterized by an increased cardiac index and decreased systemic vascular resistance. As a result, blood flow should be increased in the regional vascular beds of acromegalic patients. The aim of the study was to measure, using direct methods, blood flow and vascular resistance at the level of the brachial artery in acromegalic patients with a confirmed hyperkinetic heart syndrome. PATIENTS AND CONTROLS: Twelve patients with active acromegaly (five females, seven males; mean (+/- SD) age, 43 +/- 10 years) were studied. Twelve age- and sex-matched normal subjects served as controls. METHODS: Right heart catheterization was used to measure the cardiac index and stroke volume and to calculate systemic vascular resistance in the acromegalic patients. Brachial haemodynamics were evaluated with a two-dimensional pulsed Doppler system (double transducer probe and range-gated time system of reception). The mean diameter of the brachial artery and mean blood velocity were measured and used to calculate mean blood flow. Vascular resistance was calculated in the brachial artery as the mean arterial pressure/blood flow ratio. RESULTS: Age, body weight, height, body surface area and heart rate were similar in the acromegalic patients and controls, while mean arterial pressure was higher in patients. The cardiac index and stroke volume were increased in the acromegalic patients, at 4.08 +/- 0.47 (mean +/- SD) l/min/m2 body surface area and 116.7 +/- 19.4 ml, respectively, while systemic vascular resistance was low (12.5 +/- 2.1 U). Brachial artery diameter was similar in the patients and controls. Brachial artery mean blood velocity (P < 0.01) and mean blood flow (P < 0.05) were lower in the patients than in the controls (3.35 +/- 1.26 vs. 5.12 +/- 1.74 cm/s, and 16.4 +/- 9.4 vs. 25.6 +/- 11.6 ml/min/m2, respectively). The higher mean arterial pressure and lower mean blood flow resulted in higher forearm vascular resistance in the patients than in the controls (132 +/- 61 vs. 83.8 +/- 47 mmHg/ml/s/m2, respectively, P < 0.01). CONCLUSION: While cardiac output is increased and systemic vascular resistance is decreased in active acromegaly, direct measurement of brachial artery haemodynamics showed lower regional blood flow and increased local resistance relative to healthy controls. These results suggest a heterogeneous distribution of cardiac output in acromegaly.

[Therapeutic management of hypercholesterolemia]. / La prise en charge thérapeutique de l'hypercholestérolémie.

FUNDAMENTAL PRINCIPLES: Therapeutic management of hypercholesterolemia requires information on two fundamental aspects: the patient's lipid profile and his/her risk of coronary artery disease. RISK EVALUATION: The latest therapeutic trials have partially confirmed the LDL-cholesterol levels retained for the different guidelines, including those proposed by the ANDEM. It is clear however, that the assessment of the individual beneficial effect of primary prevention must be based on a multifactorial evaluation of risk. But there is no standardization of methodologies currently used to evaluate risk. Briefly, these methodologies use mathematical equations deducted from statistical models or noninvasive quantification of preclinical atherosclerosis. PERSPECTIVES: In the future, this strategy based on quantification of cardiovascular risk should be evaluated in a prospective study.

Coronary risk estimation and treatment of hypercholesterolemia.

BACKGROUND: Evidence-based treatment of hypercholesterolemia currently recommended for rationalizing drug prescription requires justification of treatment by randomized trials, such as the West of Scotland Coronary Prevention Study (WOSCOPS) or the Scandinavian Simvastatin Survival Study (4S), and evaluation of its benefit from the estimation of the coronary risk of each patient. METHODS AND RESULTS: The latest European guidelines and Sheffield tables apply these principles and justify the decision to treat hypercholesterolemia if the Framingham coronary multivariate risk estimate is high enough, ie, >20% risk of coronary event at 10 years in the former and >1.5% risk of coronary death per year in the latter. Nevertheless, the practice of these two recent guidelines results in discrepancies in the decision to treat, because coronary morbidity was considered in one but mortality was considered in the other, and the risk required for treating may be extrapolated from different trials (4S or WOSCOPS). CONCLUSIONS: Although the principle of targeting lipid-lowering treatment to high-risk subjects is unquestioned, further studies are needed to demonstrate that the Framingham risk profile is useful in selecting persons who are likely to benefit and to determine the place of newer risk factors and that of early noninvasive detection of atheroma in the risk estimation-based treatment.

Detection of preclinical atherosclerosis may optimize the management of hypertension.

Because of the limited ability of blood pressure elevation to predict risk, the mass drug treatment of hypertension above an arbitrary threshold may result in many subjects being overtreated. One potential way to overcome this problem is to noninvasively detect preclinical atherosclerosis. Hypertension has been shown to be associated with 1) increased intima-media thickness and more frequent plaques in extracoronary arteries, 2) more frequent calcifications in coronary arteries, 3) increased wall rigidity in the aorta and peripheral arteries, and 4) impaired endothelium dependent vasodilation and abnormal blood rheology, which are capable of promoting the conversion of atherosclerosis into atherothrombosis. The prognostic significance of these markers of preclinical atherosclerosis is supported by evidence of their association with numerous risk factors, and prevalence and incidence of cardiovascular damages. Preclinical arterial lesions also constitute ideal targets to test whether antihypertensive treatment can reverse or slow down arterial disease, and whether such a reversal produces better prevention than simply lowering blood pressure. Finally, the detection of atherosclerosis applied to large populations of mildly hypertensive subjects safely and at relatively low cost could help to better target the pharmacological treatment, given that a substantial proportion of subjects without evidence of preclinical disease may be suitable for nondrug treatment.

Fibrinogen and its relations to subclinical extracoronary and coronary atherosclerosis in hypercholesterolemic men.

The association between plasma fibrinogen and the presence of carotid, femoral, and aortic plaque (high-resolution B-mode ultrasonography) and coronary calcium deposit (ultrafast computed tomography scanner) was determined in 693 hypercholesterolemic, never-treated men free of previous or current clinical symptoms of cardiovascular disease. The number of subjects with extracoronary disease sites and coronary calcification deposits was significantly higher in the upper than in the lower tertile of fibrinogen. Plasma fibrinogen increased according to the number of diseased sites. The odds ratio of the upper to lower fibrinogen tertile for the presence of arterial lesions was 2.6 (1.7 to 4) for carotid, 2.2 (1.5 to 3.2) for aorta, 2.2 (1.5 to 3.1) for femoral, 1.8 (1.3 to 2.6) for coronary, and 3.6 (2.3 to 6.1) for one of four diseased sites. Adjustment for age, total cholesterol, HDL cholesterol, triglycerides, current smoking, and systolic pressure slightly reduced the association between fibrinogen and atherosclerosis. A synergistic effect between fibrinogen and total cholesterol/ HDL cholesterol (TC/HDL) ratio seemed to be operating on atherosclerosis, because nearly all of the individuals (98%) had a diseased site when fibrinogen and TC/HDL tertiles were the highest. This result suggests that fibrinogen is involved in the subclinical phase of extracoronary and coronary atherosclerosis and may potentiate the atherogenic effect of hyperlipidemia.

Cholesterol lowering therapy inhibits the low-flow mediated vasoconstriction of the brachial artery in hypercholesterolaemic subjects.

1. We tested whether lipid lowering treatment with HMG CoA reductase inhibitor modified the flow mediated large artery reactivity in primary pure hypercholesterolaemia. 2. Abnormalities in arterial reactivity have been described in the presence of high blood cholesterol, in particular an enhanced constriction of the brachial artery in response to acute induction of a low flow state. 3. Using pulsed-Doppler, we measured brachial artery diameter and flow velocity at rest and their changes induced by wrist occlusion before and after 3 months of double-blind treatment by pravastatin (40 mg orally) in 13 subjects and placebo in 15 others. 4. The significant decrease (P < 0.01) in diameter induced by wrist occlusion before (0.34 +/- 0.08 mm) placebo and pravastatin (0.39 +/- 0.10 mm) persisted after placebo (0.26 +/- 0.07 mm) but was abolished after pravastatin (0.07 +/- 0.05 mm). The absolute change in diameter induced by wrist occlusion was lower after than before pravastatin (P < 0.01) and lower after pravastin than after placebo (P < 0.05). Diameter during the wrist occlusion was higher after pravastatin than after placebo (4.35 +/- 0.16 vs 3.89 +/- 0.09 mm); P < 0.01). 5. These findings indicate that the lipid changes induced by pravastatin and/or some unknown but direct mechanism of the drug itself inhibit low-flow-mediated vasoconstriction associated with hypercholesterolaemia. Such effects may have important implications for the treatment of vasospasm often seen in the presence of high blood cholesterol.

Hypertension promotes coronary calcium deposit in asymptomatic men.

Despite its important role in coronary disease, coronary atherosclerosis has been poorly investigated in uncomplicated hypertension. Therefore, we evaluated the presence and amount (score) of coronary calcium with ultrafast computed tomography in 73 pairs of age-matched asymptomatic hypertensive or normotensive men. We also estimated the extent of peripheral atherosclerosis as the number of arterial sites (carotid, aortic, femoral) with echographic plaque. Compared with normotensive men, hypertensive men had more frequent coronary calcium (63% versus 47%), a higher calcium score (57 +/- 111 versus 18 +/- 38), and an odds ratio of calcium deposit of 1.95 (with confidence intervals [CI] 95%, 1.01 to 3.79) for any score and of 2.38 (95% CI, 1.02 to 5.52) or 4.84 (95% CI, 1.53 to 15.3) for scores above 50 or 100, respectively. Hypertensive men showed correlations of calcium score with age and hypertension duration but not with the height of blood pressure, and the odds ratio of calcium deposit between extensive and minor peripheral atherosclerosis was 4.67 (95% CI, 1.41 to 15.45) for any score and 8.63 (95% CI, 2.10 to 35.5) or 8.13 (95% CI, 1.64 to 40.3) for scores above 50 or 100. Thus, high blood pressure and in particular its duration rather than its value promotes the presence and overall extent of coronary calcium, a potential predictor of sudden coronary death, in parallel with the extent of peripheral atherosclerosis. The mechanisms of the interaction of hypertension and coronary calcification may be multifactorial and not specific to hypertension.