Objective-Asymmetrical dimethylarginine (ADMA) reduces nitric oxide by inhibiting nitric oxide synthase is associated with cardiovascular disease (CVD). Our study examined the association of ADMA with CVD prospectively in a healthy population-based cohort of women. Methods and Results-We measured baseline ADMA of 880 women in the Population Study of Women in Gothenburg using high-performance liquid chromatography. After adjustment for traditional risk factors, creatinine clearance, and homocysteine using Cox models, the HR (95% CI in parentheses) of CVD end points at 24 years for a 0.15 mol/L (1 SD) increase in ADMA were: all-cause mortality 1.12 (0.96, 1.32), fatal CVD 1.30 (1.04, 1.62), total CVD events 1.29 (1.09, 1.53). The top quintile (ADMA Ն0.71 mol/L) compared with the bottom four-fifths, conferred a cumulative risk 22 versus 14%, relative risk 1.75 (95% CI 1.18, 2.59) and population attributable risk 12.7% of total CVD events, and further identified individuals who are at higher than expected risk based on the SCORE and Framingham systems. Conclusions-A 0.15 mol/L increase in baseline ADMA levels is associated with approximately 30% increase in incident cardiovascular risk at 24 years in women after adjustment. ADMA levels Ն0.71 mol/L enhances CVD risk assessment in women. Key Words: asymmetrical dimethylarginine Ⅲ cardiovascular diseases Ⅲ myocardial infarction Ⅲ stroke Ⅲ women A symmetrical dimethylarginine (ADMA) has been proposed as a novel risk marker for cardiovascular disease 1-4 beause of its possible role in endothelial dysfunction, 5-7 a process thought to be pivotal in the development of arteriosclerosis. 8 Both symmetrical dimethylarginine (SDMA) and ADMA are structural analogues of the amino acid L-arginine, the substrate for the synthesis of nitric oxide by the enzyme nitric oxide synthase. 9 ADMA is an endogenous competitive inhibitor of nitric oxide synthase. 1,5 Therefore, raised levels of ADMA lead to reduced nitric acid production and hence impair endothelial function.Both ADMA and SDMA are excreted by the kidneys. Most of endogenous ADMA is broken down by the enzyme dimethylarginine dimethylaminohydrolase (DDAH) into dimethylamine and citrulline, which are also excreted through the kidneys. Hence, ADMA, as well as SDMA, accumulates in patients with renal failure. 5 However, SDMA does not inhibit nitric oxide synthase, nor is it a substrate for DDAH. Furthermore, it has been thought that the effect of homocysteine on endothelial function may be mediated through ADMA 10,11 because of the fact that homocysteine may inhibit DDAH, leading to increased ADMA levels, and hence reduced nitric oxide production.ADMA has been reported to be raised in the presence of other cardiovascular risk factors, as well as in several disease states. These cardiovascular risk factors include traditional risk factors such as blood pressure, 12-14 serum cholesterol, 6 serum triglycerides, 15 gestational diabetes, 16 insulin resistance, 17 smoking, and nontraditional risk markers such as homocysteine, 11,18,...

Patients with psoriasis had a trend towards lower levels of RCF. Significantly raised levels of homocysteine were found in patients with psoriasis compared with controls (P = 0.007). There was no correlation between homocysteine levels, RCF levels or disease activity as measured by the Psoriasis Area and Severity Index. Patients with psoriasis had higher body mass index (P < 0.004) and higher systolic blood pressure (P < 0.001) than controls. This may contribute to the excess cardiovascular mortality observed in patients with psoriasis.

The automated 3mensio Valves software demonstrated reliable, reproducible aortic annulus measurement and better predictive value for post-procedural AR, suggesting important clinical implications for pre-operative assessment of patients undergoing TAVI.

Compared to TAV, patients with BAV have higher gradients, larger annulus perimeters and more calcified valves. Higher post procedural gradient and valve underexpansion were frequently observed after CoreValve implantation. Further MSCT study is required to demonstrate the efficacy of TAVI in BAV.

BackgroundClinicians are sometimes advised to make decisions using thresholds in measured variables, derived from prognostic studies.ObjectivesWe studied why there are conflicting apparently-optimal prognostic thresholds, for example in exercise peak oxygen uptake (pVO2), ejection fraction (EF), and Brain Natriuretic Peptide (BNP) in heart failure (HF).Data Sources and Eligibility CriteriaStudies testing pVO2, EF or BNP prognostic thresholds in heart failure, published between 1990 and 2010, listed on Pubmed.MethodsFirst, we examined studies testing pVO2, EF or BNP prognostic thresholds. Second, we created repeated simulations of 1500 patients to identify whether an apparently-optimal prognostic threshold indicates step change in risk.Results33 studies (8946 patients) tested a pVO2 threshold. 18 found it prognostically significant: the actual reported threshold ranged widely (10–18 ml/kg/min) but was overwhelmingly controlled by the individual study population's mean pVO2 (r = 0.86, p<0.00001). In contrast, the 15 negative publications were testing thresholds 199% further from their means (p = 0.0001). Likewise, of 35 EF studies (10220 patients), the thresholds in the 22 positive reports were strongly determined by study means (r = 0.90, p<0.0001). Similarly, in the 19 positives of 20 BNP studies (9725 patients): r = 0.86 (p<0.0001).Second, survival simulations always discovered a “most significant” threshold, even when there was definitely no step change in mortality. With linear increase in risk, the apparently-optimal threshold was always near the sample mean (r = 0.99, p<0.001).LimitationsThis study cannot report the best threshold for any of these variables; instead it explains how common clinical research procedures routinely produce false thresholds.Key FindingsFirst, shifting (and/or disappearance) of an apparently-optimal prognostic threshold is strongly determined by studies' average pVO2, EF or BNP. Second, apparently-optimal thresholds always appear, even with no step in prognosis.ConclusionsEmphatic therapeutic guidance based on thresholds from observational studies may be ill-founded. We should not assume that optimal thresholds, or any thresholds, exist.

• Atherosclerosis underlying cardiovascular disease (CVD) is a multifactorial disease; hence, global risk estimation is necessary for making clinical decisions. • Individuals with serious inherited lipid disorders, for example, those with familial hypercholesterolaemia are at high risk and need intensive lipid management and attention to other risk factors. • Individuals with established CVD have declared themselves to be at high risk and need intensive management. • For other persons, risk estimation systems described in this chapter help to identify those with unexpectedly high or low risk and hence help to avoid undertreatment or overtreatment.

Our series of 5 cases of histologically-proven Giant cell myocarditis with concurrent CMR shows a pattern of late gadolinium enhancement which tends to be widespread involving all layers of the myocardium.

BackgroundThe 5th Joint Task Force European guidelines on cardiovascular disease (CVD) prevention recommend the measurement of carotid intima-media thickness (CIMT) in asymptomatic individuals at moderate risk (Class IIa). We aimed to evaluate the ability of CIMT to further risk stratify patients.DesignCross-sectional study.MethodsPatients aged over 18 years free of known CVD at moderate, high, or very high risk of CVD were included. The Panasonic Cardiohealth station, a semi-automated ultrasound system, was used to detect carotid plaque and measure CIMT. Elevated CIMT was defined as =/> 0.9 mm. We analyzed the percentage of those at moderate risk reclassified after addition of CIMT.ResultsTwo hundred patients were included (55% women, mean age 57 years, 12% diabetic); 64%, 23% and 13% were classified as moderate, high, and very high risk, respectively. Across these risk categories, 17%, 33%, and 46% had elevated IMT, p for trend < 0.001. With the addition of CIMT, 13.9% (95% CI: 5.7% to 22.1%) of women and 20.4% (95% CI: 8.7% to 32.1%) of men initially moderate risk were reclassified.ConclusionsCIMT measurement reclassifies a considerable percentage of those at moderate risk based on traditional risk factors alone.