Objective We evaluated the association between atherosclerotic plaque characteristics (APCs) by coronary CT angiography (CT) and lesion ischemia by fractional flow reserve (FFR). Background FFR is the gold standard for determining lesion ischemia. While APCs by CT—including aggregate plaque volume % (%APV), positive remodeling (PR), low attenuation plaque (LAP) and spotty calcification (SC)—are associated with future coronary syndromes, their relationship to lesion ischemia is unclear. Methods 252 patients (17 centers, 5 countries) [mean age 63 years, 71% males] underwent CT, with FFR performed for 407 coronary lesions. CT was interpreted for < and >50% stenosis, with the latter considered obstructive. APCs by CT were defined as: (1) PR, lesion diameter/reference diameter >1.10; (2) LAP, any voxel <30 HU; and (3) SC, nodular calcified plaque <3 mm. Odds ratios (OR) and net reclassification improvement (NRI) of APCs for lesion ischemia, defined by FFR <0.8, were analyzed. Results By FFR, ischemia was present in 151 lesions (37%). %APV was associated with a 10% increased risk of ischemia per 5% additional APV. PR, LAP and SC were associated with ischemia, with a 3-5 times higher prevalence than in non-ischemic lesions. In multivariable analyses, a stepwise increased risk of ischemia was observed for 1 [OR 4.5, p<0.001)] and ≥2 (OR 13.2, p<0.001) APCs. These findings were APC-dependent, with PR (OR 5.4, p<0.001) and LAP (OR 2.2, p=0.028) associated with ischemia, but not SC. When examined by stenosis severity, PR remained a predictor of ischemia for all lesions, while %APV and LAP were associated with ischemia for only >50% but not for <50% stenosis. Conclusions %APV and APCs by CT improve identification of coronary lesions that cause ischemia. PR is associated with all ischemia-causing lesions, while %APV and LAP are only associated with ischemia-causing lesions >50%.

A part from skeletal diseases, vitamin D deficiency is considered a risk factor for cardiovascular events and mortality. [1][2][3][4][5][6] Nevertheless, it remains unclear whether low 25-hydroxyvitamin D (25[OH]D) concentrations are a significant causal risk factor or are simply related to adverse outcomes because of reverse causation and confounding factors, such as obesity, reduced mobility with low sunlight exposure, poor nutrition, or inflammation. [1][2][3][4][5][6] Because high blood pressure (BP) has emerged as the leading risk factor for the global disease burden, it is important to evaluate whether vitamin D has a beneficial effect on lowering BP to clarify the potential role of vitamin D for public health. 7 Large observational studies and meta-analyses have shown that low 25(OH)D concentrations are a significant risk marker for arterial hypertension. 8,9 Molecular effects of vitamin D receptor activation, such as suppression of the renin-angiotensin-aldosterone system (RAAS), nephroprotective actions, or improvements in endothelial/vascular function, suggest Abstract-Vitamin D deficiency is a risk factor for arterial hypertension, but randomized controlled trials showed mixed effects of vitamin D supplementation on blood pressure (BP). We aimed to evaluate whether vitamin D supplementation affects 24-hour systolic ambulatory BP monitoring values and cardiovascular risk factors. The Styrian Vitamin D Hypertension Trial is a single-center, double-blind, placebo-controlled study conducted from June 2011 to August 2014 at the endocrine outpatient clinic of the Medical University of Graz, Austria. We enrolled 200 study participants with arterial hypertension and 25-hydroxyvitamin D levels below 30 ng/mL. Study participants were randomized to receive either 2800 IU of vitamin D3 per day as oily drops (n=100) or placebo (n=100) for 8 weeks. Primary outcome measure was 24-hour systolic BP. Secondary outcome measures were 24-hour diastolic BP, N-terminal-pro-B-type natriuretic peptide, QTc interval, renin, aldosterone, 24-hour urinary albumin excretion, homeostasis model assessment-insulin resistance, triglycerides, highdensity lipoprotein cholesterol, and pulse wave velocity. Methods Study DesignThe Styrian Vitamin D Hypertension Trial was sponsored by the Medical University of Graz, Austria, and is a single-center, double-blind, placebo-controlled, parallel-group study conducted at the Medical University of Graz, Austria. The publication of this trial adheres to the Consolidated Standards of Reporting Trials (CONSORT) 2010 statement. 29 The trial was initially registered at http://www.clinicaltrialsregister.eu (EudraCT number, 2009-018125-70) and was additionally registered at clinicaltrials.gov (ClinicalTrials.gov Identifier NCT02136771). ParticipantsEligible study participants were adults aged ≥18 years with arterial hypertension and a 25(OH)D serum concentration below 30 ng/mL (multiply by 2.496 to convert ng/mL to nmol/L). Arterial hypertension was classified in patients with an office BP of systol...

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Objective To examine sex-specific associations, if any, between per-vessel CAD extent and the risk of major adverse cardiovascular events (MACE) over a five-year study duration. Background The presence and extent of coronary artery disease (CAD) diagnosed by coronary computed tomography angiography (CCTA) is associated with increased short-term mortality and MACE. Nevertheless, some uncertainty remains regarding the influence of gender on these findings. Methods 5,632 patients (mean age 60.2 + 11.8 years, 36.5% female) from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry were followed over the course of 5 years. Obstructive CAD was defined as ≥50% luminal stenosis in a coronary vessel. Using Cox proportional-hazards models, we calculated the hazard ratio (HR) for incident MACE among women and men, defined as death or myocardial infarction (MI). Results Obstructive CAD was more prevalent in men (42% vs. 26%, p<0.001) whereas women were more likely to have normal coronary arteries (43% vs. 27%, p<0.001). There were a total of 798 incident MACE events. After adjustment, there was a strong association between increased MACE risk and non-obstructive CAD (HR 2.16 for women, 2.56 for men, p<0.001 for both), obstructive one-vessel CAD (HR 3.69 and 2.66, p<0.001), two-vessel CAD (HR 3.92 and 3.55, p<0.001) and three-vessel/left-main CAD (HR 5.94 and 4.44, p<0.001). Further exploratory analyses of atherosclerotic burden did not identify gender-specific patterns predictive of MACE. Conclusion In a large prospective CCTA cohort followed long-term, we did not observe an interaction of gender for the association between MACE risk and increased per-vessel extent of obstructive CAD. These findings highlight the persistent prognostic significance of anatomic CAD subsets as detected by CCTA for the risk of MACE in both women and men.

Coronary CT angiography provides incremental prognostic utility for prediction of mortality and non-fatal myocardial infarction for asymptomatic individuals with moderately high CACS, but not for lower or higher CACS.

Homoarginine (hArg) is an endogenous, nonproteinogenic amino acid which differs from arginine by an additional methylene (CH2) group in the backbone. In this brief narrative review, we summarize the current literature on hArg in the renal and cardiovascular systems. Epidemiological studies have identified low hArg levels as an independent risk marker for cardiovascular, cerebrovascular, and renal diseases as well as for mortality. The relatively low correlation of hArg with established cardiovascular risk factors underlines its great potential as an emerging biomarker to improve risk prediction because plasma hArg concentrations might reflect previously unrecognized pathophysiological processes. hArg may be involved in the pathogenesis of various diseases due to its effects on nitric oxide (NO) and energy metabolism. In view of its structural similarities with arginine, it has been proposed that hArg impacts on arginine metabolism and subsequently also on NO synthesis. The key enzyme for hArg synthesis, arginine:glycine amidinotransferase (AGAT), is involved in the synthesis of energy metabolites including guanidinoacetate, the precursor of creatine. Therefore, the involvement of hArg in energy metabolism could partially explain the close association between hArg and cardiovascular diseases such as heart failure. Whether hArg supplementation or modification of key enzymes of hArg metabolism such as AGAT activity is effective for the treatment of chronic diseases remains to be elucidated.

Objective To examine long-term prognosis of a zero coronary artery calcium (CAC) score among asymptomatic individuals and its associated warranty period. Background Emerging evidence supports CAC=0 as a favorable cardiovascular short-to-intermediate term prognostic factor. Methods 9715 individuals undergoing CAC imaging were stratified by age, Framingham risk score (FRS) and Adult Treatment Panel III (NCEP ATP III) categories and followed for a mean of 14.6 (12.9–16.8) years. Cox regression, area under the receiver operating characteristic curve (AUC) and net reclassification information (NRI) were used to assess all-cause mortality, discrimination and reclassification of CAC=0 compared with FRS and NCEP ATP III, respectively. A warranty period was pre-defined as <1% annual mortality rate. Vascular age was estimated by linear regression. Results Among 4864 individuals with baseline CAC=0 (mean age 52.1±10.8 years; 57.9% male), 229 deaths occurred. The warranty period of CAC=0 was almost 15 years for individuals at low and intermediate risk with no significant differences regarding age and gender. CAC=0 was associated with a vascular age of 1, 10, 20, and 30 years below chronologic age for individuals between 50–59, 60–69, 70–79, and ≥80 years, respectively. CAC score was the strongest predictor of death (HR 2.67, 95% CI 2.29–3.11) that enabled discrimination and consistent reclassification beyond FRS (AUC 0.71 vs. 0.64, p<0.001) and NCEP ATP III (AUC 0.72 vs. 0.64, p<0.001). Conclusions CAC=0 confers a 15-year warranty period against mortality among individuals at low-to-intermediate risk, which is unaffected by age or gender. Furthermore, in individuals considered at high-risk by clinical risk scores the presence of CAC=0 confers better survival than in individuals at low-to-intermediate risk but with any CAC.

Due to its predictive potential and inexpensive determination, assessment of high neutrophil counts may represent an important marker, possibly improving cardiovascular mortality risk prediction.