Objective: Inducible myocardial ischemia is influenced by contributions of both the epicardial artery and the coronary microcirculation. Experimental studies have found adverse microcirculatory remodeling to occur downstream of severe coronary stenoses. Coronary physiology studies in patients contradict the experimental findings, as the minimal microvascular resistance is not modified by stenoses. The objective was to determine whether microcirculatory remodeling occurs downstream of coronary stenoses in the human coronary circulation. Approach and Results: Myocardium corresponding to 115 coronary arteries of 55 deceased patients was investigated. Histopathologic staining of the microcirculation was performed using antibodies against SMA-α (smooth muscle actin-α) and CD31, to stain arterioles and capillaries, respectively. The following parameters were analyzed: ratio between lumen and vesel area, ratio between lumen and vessel diameter (both ratios for arterioles of <40, 40–100, and 100–200 µm diameter), arteriolar density, and capillary density. From the 55 patients, 32 pairs of an unobstructed coronary artery and a coronary artery with a stenosis were formed. No statistically significant differences between any of the microcirculatory parameters were found. A confirmatory unpaired analysis compared 3 groups: (1) coronary arteries in patients without coronary artery disease (n=53), (2) unobstructed coronary arteries in patients with a stenosis in one of the other coronary arteries (n=23), and (3) coronary stenoses (n=39). No statistically significant differences were observed between the groups. Conclusions: The microcirculation distal to noncritical stenoses does not undergo structural remodeling in the human coronary circulation.

Introduction: Coronary arterial stenosis may impair myocardial perfusion with myocardial ischemia and associated morbidity and mortality as result. The myocardial fractional flow reserve (FFR) is clinically used as a stenosis-specific index. Aim: This study aims to identify the relation between the FFR and the degree of coronary arterial stenosis using a simple mathematical model of the coronary circulation. Methods: A mathematical model of the coronary circulation, including an arterial stenosis of variable degree, was developed. The relation between the FFR and the degree of stenosis (defined as the fractional cross sectional area narrowing) was investigated, including the influence of the aortic and venous pressures and the capillary resistance. An additional study concerning 22 patients with coronary artery disease permits comparison of clinical data and in silico findings. Results: The FFR shows an S-shaped relationship with the stenosis index. We found a marked influence of venous and aortic pressure and capillary resistance. The FFR is accompanied by a clinically relevant co-metric (FFR C), defined by the Pythagorean sum of the two pressures in the definition formula for FFR. In the patient group the FFR C is strongly related to the post-stenotic pressure (R = 0.91). The FFR C requires establishment of a validated cutoff point using future trials. Conclusion: The S-shaped dependence of FFR on the severity of the stenosis makes the FFR a measure of the ordinal scale. The marked influences of the aortic and venous pressures and the capillary resistance on the FFR will be interpreted as significant variations in intra-and inter-individual clinical findings. These fluctuations are partly connected to the neglect of considering the FFR C. At otherwise identical conditions the FFR as measured at baseline differs from the value obtained during hyperemic conditions. This expected observation requires further investigation, as the current hyperemia based evaluation fails to take advantage of available baseline data.

Background Diet, alcohol, cigarette smoking, physical inactivity, and body mass index have been studied as risk factors for renal cell cancer (RCC). The joint effects of these lifestyle factors, captured as Healthy Lifestyle Index (HLI), were examined in one previous study. This study aims to investigate the association between HLI score and RCC risk in the prospective Netherlands Cohort Study (NLCS). Methods A case-cohort analysis (3,767 subcohort members, 485 cases) was conducted using NLCS data (n = 120,852). Data on aforementioned risk factors was used to calculate HLI score, ranging 0–20, with higher scores reflecting healthier lifestyles. RCC occurrence was obtained by record linkage to cancer registries. Multivariable-adjusted proportional hazard models were used to calculate Hazard Ratios (HR) and 95% Confidence Intervals (95%CI). Results Compared to participants in the unhealthiest HLI category, participants within the healthiest category had a lower RCC risk (HR = 0.79, 95%CI = 0.56–1.10, p for trend 0.045). A standard deviation (± 3-unit) increase in HLI score was not statistically significantly associated with a lower RCC risk (HR = 0.92, 95%CI = 0.83–1.01). This association was stronger after excluding diet or alcohol from the score, although confidence intervals overlap. Conclusions Adherence to a healthy lifestyle was weakly, though not statistically significantly, associated with a lower RCC risk.

Background: There is growing evidence from high-income countries suggesting that hypertension developed in childhood and adolescence persists into adulthood. The objective of this study was to investigate the incidence and risk factors of high blood pressure (BP) in urban black children. Methods:We used data from the Birth to Twenty (BT20R) cohort in Johannesburg, South Africa constituting of children born in 1990 and who had their growth, development and blood pressure measured at six follow-up periods over the course of 13 years. High BP was classified as at least 95th percentile for age, sex and height. Incidence rate of high BP was calculated using survival analysis and risk factors were determined by use of Cox proportional hazard regression.Results: Over a follow-up period of 13 years, the overall incidence rate of high BP was 57 cases per 1000 personyears (95% CI 53.2-61.1). Risk for incident high BP increased with rapid relative weight gain in early childhood (hazard ratio ¼1.11, 95% CI 1.00-1.22), mid-childhood (hazard ratio ¼ 1.13, 95% CI 1.03-1.24) and adolescence (hazard ratio ¼ 1.21, 95% CI 0.99-1.47). Maternal parity significantly increased the risk for incident high BP (hazard ratio ¼ 1.08, 95% CI 1.01-1.15). Conclusion:Maternal parity and relative weight gain were determinants for incident high blood pressure in urban black South African children and adolescents. To reduce the high incidence and the disease burden of high BP, national programs should focus on promoting healthy lifestyle in early stages of life to prevent rapid weight gain and later cardiovascular disease risk. Further research is required to investigate whether incident high BP in childhood predict clinical outcomes in adulthood.