Highly accurate coronary angiography with submillimetre, 16 slice computed tomography.

OBJECTIVE: To assess submillimetre coronary computed tomographic angiography (CTA) in comparison with invasive quantitative coronary angiography as the gold standard and to examine the effect of significant coronary artery calcification (CAC), which is known to impede lumen visualisation, on the accuracy of the examination. METHODS: After invasive coronary angiography, 58 patients underwent coronary imaging with a GE Lightspeed 16 computed tomography (CT) system. CAC was quantified after an ECG triggered acquisition with a low tube current. Coronary CTA was performed with retrospective ECG gating and a 16 x 0.63 mm collimation and was reconstructed with an effective 65-250 ms temporal resolution. All 13 major coronary artery segments were evaluated for the presence of > or = 50% stenosis, and compared with the gold standard. RESULTS: One patient moved and could not be evaluated. All segments (except occluded segments) were evaluated for 57 patients. Overall the accuracy of coronary CTA for detection of > or = 50% stenosis was: sensitivity 83%, specificity 97%, positive predictive value 80%, and negative predictive value 97%. The number of diseased coronary arteries was correctly diagnosed in 34 of 38 (89%) patients overall. Altogether 21 of 57 (37%) patients had a CAC score > or = 400, which was predefined as representing significant CAC. Excluding these patients from the analysis improved the accuracy of coronary CTA to a sensitivity of 89%, specificity 98%, positive predictive value 79%, and negative predictive value 99%. CONCLUSIONS: Non-invasive coronary angiography with submillimetre CT is reliable and accurate. It appears that a subgroup of patients may be selected based on CAC score in whom the investigation has even higher accuracy. Coronary CTA has reached the stage where it should be considered for a clinical role. Further research is required to define this role.

Three dimensional volume quantification of aortic valve calcification using multislice computed tomography.

OBJECTIVE: To assess a new multislice computed tomography (CT) technique for three dimensional quantification of aortic valve calcification volume (3D AVCV) and to study the relation between stenosis and calcification of the aortic valve. METHODS: 50 patients with echocardiographic calcification of the aortic valve underwent two separate ECG triggered multislice CT for quantification of 3D AVCV. The agreement between the two 3D AVCV scores was assessed and 3D AVCV was compared with echocardiographic markers of severity of aortic stenosis. RESULTS: Overall the level of agreement between the two 3D AVCV scores was excellent (median interscan variability 7.9% (interquartile range 10.1); correlation coefficient, r = 0.99; repeatability coefficient 237.8 mm3 (limits of agreement -393 to 559 mm3)). However, the magnitude of the 3D AVCV did influence the interscan variability. The 3D AVCV correlated closely with the maximal predicted transvalvar gradient (r2 = 0.77) and aortic valve area (r2 = 0.73). CONCLUSIONS: Multislice CT provides a technique for quantifying 3D AVCV that has good reproducibility. There is a close non-linear relation between echocardiographic parameters of severity of valve stenosis and 3D AVCV scores.

1 alpha,25-dihydroxyvitamin D(3) inhibits angiogenesis in vitro and in vivo.

Modulation of angiogenesis is now a recognized strategy for the prevention and treatment of pathologies categorized by their reliance on a vascular supply. The purpose of this study was to evaluate the effect of 1 alpha,25-dihydroxyvitamin D(3) [1, 25(OH)(2)D(3)], the active metabolite of vitamin D(3), on angiogenesis by using well-characterized in vitro and in vivo model systems. 1,25(OH)(2)D(3) (1 x 10(-9) to 1 x 10(-7) mol/L) significantly inhibited vascular endothelial growth factor (VEGF)-induced endothelial cell sprouting and elongation in vitro in a dose-dependent manner and had a small, but significant, inhibitory effect on VEGF-induced endothelial cell proliferation. 1, 25(OH)(2)D(3) also inhibited the formation of networks of elongated endothelial cells within 3D collagen gels. The addition of 1, 25(OH)(2)D(3) to endothelial cell cultures containing sprouting elongated cells induced the regression of these cells, in the absence of any effect on cells present in the cobblestone monolayer. Analysis of nuclear morphology, DNA integrity, and enzymatic in situ labeling of apoptosis-induced strand breaks demonstrated that this regression was due to the induction of apoptosis specifically within the sprouting cell population. The effect of 1,25(OH)(2)D(3) on angiogenesis in vivo was investigated by using a model in which MCF-7 breast carcinoma cells, which had been induced to overexpress VEGF, were xenografted subcutaneously together with MDA-435S breast carcinoma cells into nude mice. Treatment with 1,25(OH)(2)D(3) (12.5 pmol/d for 8 weeks) produced tumors that were less well vascularized than tumors formed in mice treated with vehicle alone. These results highlight the potential use of 1,25(OH)(2)D(3) in both the prevention and regression of conditions characterized by pathological angiogenesis.

Arterial hypotension: prevalence of low blood pressure in the general population using ambulatory blood pressure monitoring.

BACKGROUND: Chronic constitutional hypotension has been described in a proportion of the population, and has a symptom complex ascribed to it. The true prevalence of low blood pressure in the normal population has not been defined. AIM OF STUDY: This study was undertaken to determine the prevalence of low blood pressure states, as measured using ambulatory blood pressure monitoring, in a general population cohort, and to determine the association between low blood pressure and clinical and demographic variables. PATIENT POPULATION: The population enrolled were a cohort of mainly urban dwelling Irish subjects, either employees or spouses of employees of a major national bank. METHODS: Subjects had an ambulatory blood pressure monitor fitted between 09.00 and 12.00 and wore the monitor for 24 hours. The subjects also filled out a detailed lifestyle questionnaire, and kept an activity diary. Blood was drawn for serum electrolyte estimation. RESULTS: A total of 254 subjects were included, 49% of whom demonstrated hypotensive events. Hypotensive means and individual hypotensive values were more frequently found in women, and occurred in a group of individuals with a distinct body habitus, specifically thin subjects, with a lower creatinine suggesting a smaller muscle mass. Hypotensive events in these subjects were associated with a low risk cardiovascular profile, in that subjects who displayed these events had a lower blood pressure, a lower weight and were less likely to have a positive family history of hypertension or vascular disease. CONCLUSION: Hypotension is common in the general population and is associated with a distinct body habitus. It carries a generally benign cardiovascular risk factor profile.

Is elevation of clinic blood pressure in patients with white coat hypertension who have normal ambulatory blood pressure associated with target organ changes?

BACKGROUND: The issue as to whether white coat hypertension is a pathologically significant entity, with associated target organ changes, or that the condition carries the same risk for target organ involvement as normotension, is undecided. Previous studies which have shown pathological correlates between white coat hypertension and target organ damage have not controlled for the most obvious confounder, mean 24 h blood pressure (BP). METHODS AND RESULTS: In this study we retrospectively identified 33 age and sex-matched pairs, one group with normal BP, the other with white coat hypertension. The white coat hypertensive group showed significantly greater left ventricular mass indexed for body surface area than normal controls (99.0 g/m2 vs 78.3 g/m2, P < 0.001). The population was then further matched for 24-h mean BP (20 pairs), and was again compared for cardiac muscle changes. The significantly increased left ventricular mass index in the white coat population remained after controlling for 24-h mean BP (101.1 g/m2 vs 81.0 g/m2, P < 0.021). CONCLUSION: White coat hypertension is indeed associated with a larger left ventricular muscle mass than normotensives and these changes are independent of the actual 24-h BP load, and may reflect increased BP lability, sympathetic nervous system derangement, or a genetic propensity in people with white coat hypertension to stress-related hypertensive reactions, as part of a pre-hypertensive state.

Can heart rate predict blood pressure response to anti-hypertensive drug therapy?

The use of heart rate in clinical practice is limited by its variability under measurement situations. The mean heart rate on ambulatory monitoring provides a more robust statistic for clinical use. We examined the relationship between mean heart rate on initial referral ambulatory blood pressure monitoring (ABPM) to the BP-lowering efficacy of the four main groups of anti-hypertensive medications, in a referral hypertensive population. Patients were retrospectively identified by review of the BP database, and data collected from the initial referral BP monitor off medication, and the subsequent ABPM after treatment with either beta-blockers, diuretics, calcium antagonists or angiotensin-converting enzyme (ACE) inhibitors. The change in mean arterial BP from the initial to the subsequent ABPM (ie, as a result of treatment) was correlated with the mean heart rate on the initial ABPM. A moderate association was found for initial daytime heart rate and BP response to beta-blockers (r = 0.24, P = 0.02), and ACE inhibitors (r = 0.14, P = 0.05). No such association was found for calcium antagonists or diuretics. When the groups were divided into those with a mean daytime heart rate <75 and > or =75 beats per min, BP reduction from beta-blocker and ACE inhibitor therapy was significantly greater in those patients with a higher daytime heart rate. We conclude that average daytime heart rate on pre-treatment ABPM can be useful as a predictor of BP response to beta-blockade or ACE inhibition.