Tissue blood flow (TBF), its percent distribution and glomerular blood flow (GBF) were measured using labelled microspheres 15 micrometer in diameter (M) and chicken red blood cells (CRBC) at perfusion pressures (PP) of 17.3, 12.8 and 8.0 kPa (130, 95 and 60 mm Hg) in isolated alloperfused dog kidneys. Renal blood flow (RBF) was never interrupted during the isolation. Experiments with M showed a marked inequality of the tissue blood flow in different parts of the renal cortex at a constant PP of 17.3 kPa. TBF was highest in the outermost quarter and lowest in the juxtamedullary one. Using CRBC, a homogeneous TBF was observed in the outer 3/4 of the renal cortex with a lower flow in the innermost quarter. With M, a typical percent "redistribution" of TBF and GBF into the inner cortical regions was indicated during PP reduction. With CRBC, this phenomenon was observed only at PP below the range of RBF autoregulation (8.0 kPa) and was much less conspicuous than with M. The smaller size and higher elasticity of CRBC as compared with M, may result in a more realistic reflection of cortical blood flow distribution. The GBF of outermost superficial glomeruli decreases, even with CRBC, with each PP reduction, the difference exhibiting only a 5% significance level. The lower limit of BF autoregulation in these glomeruli seems to be somewhat higher than that of total RBF autoregulation.
The uptake of 42K, 86Rb and 201Tl by non-ischaemic and ischaemic myocardium was determined in rats with coronary artery ligature lasting 10, 30, 60 and 120 min, and in control rats without ischaemia. Whereas the myocardial concentration of 201Tl and 42K in control rats was similar and higher than that of 86Rb, 201Tl was superior to the other two radionuclides due to its significantly higher accumulation in non-ischaemic myocardium and the higher ratio of non-ischaemic to ischaemic radioactivity. The 86Rb accumulation in non-ischaemic myocardium and non-ischaemic/ischaemic ratio began to decrease from its maximum at 10 min. 201Tl, 42K and 86Rb blood levels in intact animals decreased rapidly after intravenous injection to low and nearly stabilized values at 5 min. Na+K+-ATPase activity in the ischaemic myocardium was high in the acutely ischaemic myocardium and decreased to below control levels after 4 h of ischaemia; changes in activity could not influence the low uptake of potassium analogues in fresh ischaemic myocardium.
Introduction: Genetic predisposition for CAD is well established. Polygenic risk scores are emerging as tools which attempt to quantify the genomic component of an individual’s risk for CAD. However, clinical utility for individual risk stratification is unclear. Hypothesis: 180 SNPs previously identified in Caucasian Genome Wide-Association Studies for CAD were used to construct a weighted restricted polygenic risk score (PRS; normalized range 11.18 -17.58). This study hypothesizes that high PRS (>=85th percentile) is associated with high (>400) coronary artery calcium (CAC) score, & a low PRS(< 85th percentile) is associated with low (<100) CAC. Methods: Between January 2018 and March 2020, 21,784 patients underwent CAC screening and/or PRS testing. Caucasian patients with both PRS and CAC scores were reviewed. Patients with CAC 100-400 were excluded. Fisher’s exact test for high/low PRS and high/low CAC was utilized. Results: 2,752 patients were identified to have low (<100) or high (>400) CAC; 306 (11.1%) had a high CAC (table 1). Odds ratio of high PRS associated with high CAC and low PRS associated with low CAC was 1.54 (95% CI: 1.07-2.19; p=0.017). Conclusion: Our real-world experience in a Caucasian cohort shows that high PRS is associated with a high CAC, as is a low PRS with low CAC. Concordance between PRS and CAC lends support for incorporating PRS in the clinical setting, especially for early identification of individuals at high risk for CAD. Larger, ethnically diverse studies are needed.
Introduction: Genetic predisposition for CAD is well established. Polygenic risk scores are emerging as tools to quantify the genomic component of an individual’s risk for CAD. However, their clinical utility for individual risk stratification is unclear. Hypothesis: 180 SNPs previously identified in Caucasian Genome Wide-Association Studies for CAD were used to construct a weighted restricted polygenic risk score (PRS; normalized range 11.18 -17.58). This study hypothesizes that a low PRS (<85th percentile) is associated with coronary calcium score (CAC) of zero. Methods: Between January 2018 & March 2020, 21,784 patients underwent CAC screening and/or PRS testing. Caucasian patients with both PRS and CAC scores were identified. Fisher’s exact test was utilized to test the association between low PRS and CAC score of zero. Results: 3,197 Caucasian patients had both PRS and CAC calculated, 1597 (49.9%) of whom had CAC greater than zero. Characteristics are summarized in table 1. Odds ratio of low PRS associated with CAC zero was 1.34 (95% CI 1.08 - 1.67; p=0.0079). Conclusions: In our Caucasian cohort, there is a statistically significant correlation between a low PRS and absence of coronary artery calcium. This is a real-world analysis incorporating genomic data for individual CAD risk stratification. Further studies on a larger, ethnically diverse cohort are needed.
Introduction: Genetic predisposition for CAD is well established. Polygenic risk scores are emerging as tools which attempt to quantify the genomic component of an individual’s risk for CAD. However, their clinical utility for individual risk stratification is unclear. Hypothesis: 180 SNPs previously identified in Caucasian Genome Wide-Association Studies for CAD were used to construct a weighted restricted polygenic risk score (PRS; normalized range 11.18 -17.58). This study hypothesizes a gender-specific association between high PRS (>=85th percentile) and high coronary artery calcium score (CAC) score, defined as >400. Methods: Between January 2018 & March 2020, 21,784 patients underwent CAC screening and/or PRS testing. Caucasian patients with both PRS and CAC scores were identified. Fisher’s exact test was utilized to test the association between high PRS and high CAC in men and women. Results: Both PRS and CAC were available for 3,197 Caucasian patients, out of which 2,106 (65.8%) were women (figure 1: gender adjusted PRS distribution). Odds ratio of high PRS and high CAC was 1.64 (95% CI: 0.86-2.97; p >0.05) in women and 1.59 (95% CI: 0.98 - 2.53; p>0.05) in men. Conclusions: There is no statistically significant, gender-specific association between high PRS and high CAC in our Caucasian cohort. However, there is a trend suggestive of a positive correlation in women. This clinical data is the first of its kind in a real world setting on the use of PRS for CAD risk assessment. Larger, ethnically diverse studies are needed.
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