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Secondary causes of hypertension can affect over 10% of those patients diagnosed with hypertension, and the workup can encompass a wide variety of pathologies. Here we present a case of secondary hypertension found in a young physician who, fortunately, had both of these two entities diagnosed via fortuitous imaging performed for non-diagnostic reasons. This case involves a relatively common cause of secondary hypertension (renovascular) and a more obscure cause (paraganglioma). We outline evidencebased surgical and perioperative management of paragangliomas, as well as the medical management of renovascular hypertension. This case is unique in that it involves both elements of secondary hypertension and presents difficult management decisions.

Dietary sodium and blood pressure regulation differs between normotensive men and women, an effect which may involve endothelial production of nitric oxide (NO). Therefore, we tested the hypothesis that differences in the NO component of endothelium-dependent vasodilation between low and high dietary sodium intake depend on sex. For 5 days prior to study, healthy adults consumed a controlled low-sodium diet (10 mmol/day, n = 30, mean age ± SE: 30 ± 1 yr, 16 men) or high-sodium diet (400 mmol/day, n = 36, age 23 ± 1 yr, 13 men). Forearm blood flow (FBF, plethysmography) responses to brachial artery administration of acetylcholine (ACh, 4 μg·100 ml tissue−1·min−1) were measured before and after endothelial NO synthase inhibition with NG-monomethyl-l-arginine (l-NMMA, 50 mg bolus + 1 mg/min infusion). The NO component of endothelium-dependent dilation was calculated as the response to ACh before and after l-NMMA accounting for changes in baseline FBF: [(FBF ACh − FBF baseline) − (FBF AChL-NMMA − FBF baselineL-NMMA)]. This value was 5.7 ± 1.3 and 2.5 ± 0.8 ml·100 ml forearm tissue−1·min−1 for the low- and high-sodium diets, respectively (main effect of sodium, P = 0.019). The sodium effect was larger for the men, with values of 7.9 ± 2.0 and 2.2 ± 1.4 for men vs. 3.1 ± 1.3 and 2.7 ± 1.0 ml·100 ml forearm tissue−1·min−1 for the women ( P = 0.034, sex-by-sodium interaction). We conclude that the NO component of endothelium-dependent vasodilation is altered by dietary sodium intake based on sex, suggesting that endothelial NO production is sensitive to dietary sodium in healthy young men but not women.

AbstractBACKGROUNDSoluble intercellular adhesion molecule 1 (sICAM-1) is associated with endothelial dysfunction and clinical cardiovascular disease. We investigated the relationship of subclinical atherosclerosis with sICAM-1 concentration.METHODSsICAM-1 concentration was assayed at year 15 of the Coronary Artery Risk Development in Young Adults (CARDIA) Study (black and white men and women, average age 40 years). We assessed progression of coronary artery calcification (CAC) through year 20 (n = 2378), and both carotid artery stenosis (n = 2432) and intima-media thickness (IMT) at year 20 (n = 2240).RESULTSMedian sICAM-1 was 145.9 μg/L. Among a subgroup with advanced atherosclerotic plaque (either CAC or stenosis), IMT was 0.010 (95% CI 0.003–0.017 mm) higher per SD of sICAM-1 (44 μg/L) in a model adjusted for age, race, sex, clinic, smoking, exercise, body size, education, blood pressure, antihypertensive medication, plasma lipids, and cholesterol-lowering medication. With the same adjustment, the odds ratio (OR) for the presence of year-20 carotid artery stenosis per SD of sICAM-1 was 1.12 (95% CI 1.01–1.25, P < 0.04), whereas for occurrence of CAC progression the OR was 1.16 (1.04–1.31, P < 0.01). The associations with CAC and carotid stenosis were strongest in the top 20th of the sICAM-1 distribution.CONCLUSIONSsICAM-1 concentration may be an early biomarker that indicates changes in the artery wall that accompany atherosclerosis, as well as the presence of advanced plaque in the coronary and carotid arteries. This finding holds in people with low total burden of atherosclerosis, decades before the development of clinical CVD.

Abstract Ischemic stroke (IS) is among the leading causes of death in Western countries. There is a significant genetic component to IS susceptibility, especially among young adults. To date, research to identify genetic loci predisposing to stroke has met only with limited success. We performed a genome-wide association (GWA) analysis of early-onset IS to identify potential stroke susceptibility loci. The GWA analysis was conducted by genotyping 1 million SNPs in a biracial population of 889 IS cases and 927 controls, ages 15–49 years. Genotypes were imputed using the HapMap3 reference panel to provide 1.4 million SNPs for analysis. Logistic regression models adjusting for age, recruitment stages, and population structure were used to determine the association of IS with individual SNPs. Although no single SNP reached genome-wide significance (P < 5 × 10−8), we identified two SNPs in chromosome 2q23.3, rs2304556 (in FMNL2; P = 1.2 × 10−7) and rs1986743 (in ARL6IP6; P = 2.7 × 10−7), strongly associated with early-onset stroke. These data suggest that a novel locus on human chromosome 2q23.3 may be associated with IS susceptibility among young adults.

Acute β-adrenergic blockade increases aortic wave reflection; however, the mechanisms remain unclear. Evidence suggests that β-adrenergic receptor sensitivity in the peripheral vasculature differs between sexes. Therefore, the goal of this study was to examine whether β-adrenergic blockade alters aortic wave reflection to a similar extent in young men and women. In 31 subjects (16 men and 15 women; 26±1 years) noninvasive aortic pressure waveforms were synthesized from high-fidelity radial pressure waveforms via applanation tonometry before and during systemic β-blockade (0.25 mg/kg bolus, followed by 0.004 mg/kg per minute of continuous infusion of propranolol). β-Blockade increased aortic augmentation index and wave reflection amplitude (aortic augmented pressure) in both sexes ( P <0.01). Although the increase in augmentation index was not significantly different between sexes (7.5±1.1% versus 4.6±1.5%; P =0.07), the increase in aortic augmented pressure was greater in women compared with men (2.8±0.5 versus 1.4±0.5 mm Hg; P <0.05). Aortic augmentation index adjusted for a heart rate of 75 bp increased in women (4.1±1.1%; P <0.05) after β-blockade, whereas it was unchanged in men (0.6±1.3%; P =0.33). Moreover, the change in aortic augmentation index was inversely associated with the change in heart rate only in men ( r =−0.54; P <0.05). Our data suggest that aortic wave reflection is increased to a greater extent in women after systemic β-blockade, and enhanced aortic wave reflection appears to be mediated by a reduced heart rate in men, whereas the mechanism is unclear in women.

Interleukin- (IL-) 17 is important in the development of asthma and host defense against pneumococci. We determined the role of IL-17 in the risk of pneumococcal pneumonia. We challenged mice intranasally with a bioluminescentStreptococcus pneumoniaestrain after sensitization and challenge with ovalbumin (OVA). We measured the levels of cytokines, including IL-17 (pg/mL), in the lung homogenate in experimental mice with and without OVA sensitization/challenge, as well as those with and without pneumococcal pneumonia. IL-17 levels were significantly lower in OVA-sensitized/challenged mice (9.69±1.49), compared to the control mice (20.92±1.82,P< 0.001). In our overall analysis, including IL-4 and IL-17 levels and OVA sensitization/challenge, IL-4 levels (OR: 81.9, 95%CI: 4.3–1523 per increment of 1.0 pg/mL,P= 0.003) were more significant than IL-17 levels (OR: 1.1, 95%CI: 1.03–1.17 per increment of 1.0 pg/mL,P= 0.003) in determining the risk of pneumococcal pneumonia. IL-17 levels result in a much smaller impact on the risk for pneumococcal pneumonia, compared to IL-4 levels.

This paper begins with a patient perspective from the first author. Faced with cascading health problems, this author describes her gradual embrace of alternative treatments. While these improved her health, they also set her apart and prompted antagonism from those in conventional medicine. She found she was not alone in benefiting from a more open view of healing, and not alone in being buffeted by the opposing medical views. Two invited commentaries from medical professionals follow, as well as the first author’s response.

Abstract Background: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium. Methods: Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression. Results: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08–1.14, P = 7 × 10−18) for invasive breast cancer and 1.10 (95% CI = 1.01–1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR = 1.07, 95%CI = 0.99–1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)-positive disease (per-allele OR = 1.16, 95% CI = 1.12–1.20, P = 1 × 10−18 vs. OR = 1.03, 95% CI = 0.99–1.07, P = 0.2 for PR-negative disease; Pheterogeneity = 2 × 10−7); heterogeneity by ER status was not observed (P = 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) = 1.20 (1.14–1.25), 1.13 (1.09–1.16), and 1.04 (0.99–1.08) for grade 1, 2, and 3/4, respectively; Ptrend = 5 × 10−7]. Conclusion: 5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer. Impact: Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants. Cancer Epidemiol Biomarkers Prev; 20(10); 2222–31. ©2011 AACR.