Description: A successful pregnancy requires an accommodating environment. Salt and water availability are critical for plasma volume expansion. Any changes in sodium intake would alter aldosterone, a hormone previously described beneficial in pregnancy. To date, it remains ambiguous whether high aldosterone or high salt intake is preferable. We hypothesized that increased aldosterone is a rescue mechanism and appropriate salt availability is equally effective in maintaining a normotensive blood pressure (BP) phenotype in pregnancy. We compared normotensive pregnant women (n=31) throughout pregnancy with young healthy female individuals (n=31–62) and performed salt sensitivity testing within the first trimester. Suppression of urinary tetrahydro-aldosterone levels by salt intake as measured by gas chromatography–mass spectrometry and urinary sodium excretion corrected for creatinine, respectively, was shifted toward a higher salt intake in pregnancy ( P 〈0.0001). In pregnancy, neither high urinary tetrahydro-aldosterone nor sodium excretion was correlated with higher BP. In contrast, in nonpregnant women, systolic BP rose with aldosterone ( P 〈0.05). Testing the impact of salt on BP, we performed salt sensitivity testing in a final cohort of 19 pregnant and 24 nonpregnant women. On salt loading, 24-hour mean arterial pressure rose by 3.6±1.5 and dropped by –2.8±1.5 mm Hg favoring pregnant women ( P 〈0.01; 2 =6.04; P 〈0.02). Our data suggest first that salt responsiveness of aldosterone is alleviated in conditions of pregnancy without causing aldosterone-induced hypertension. Second, salt seems to aid in BP lowering in pregnancy for reasons incompletely elucidated, yet involving renin suppression and potentially placental sensing mechanisms. Further research should identify susceptible individuals and clarify effector mechanisms.

Description: Retinal arteriolar narrowing reflects aging, hypertension, chronic kidney disease (CKD), and other vascular processes. We examined the predictive value of retinal arteriolar narrowing alone and in combination with albuminuria on renal disease progression in CKD. A white CKD stage 2 to 4 cohort of 164 men and women (60.8±13.8 years) underwent retinal photography and determination of albuminuria. The calibers of all retinal arterioles were measured after digital conversion of the photographs. Cases of incident renal end points defined as 50% renal function loss and start of renal replacement therapy were identified and validated by case record reviews. Over an average period of 1410 (range, 106–1606) days, 25 patients with CKD had incident renal end points. Kaplan–Meier analysis revealed that patients with CKD within the tertile of narrowest arterioles had more renal end points (log-rank P 〈0.001). Cox regression analysis confirmed this before (β=1.183±0.411) and after adjusting for age and baseline renal function (β=1.204±0.416). With respect to renal end points, a significant interaction was present between narrow arterioles and albuminuria. The relative risk for renal end points of narrow arterioles was 3.7 (1.7–8.4), of albuminuria was 5.4 (2.5–12.0), and of combined narrow arterioles and albuminuria was 16.2 (4.6–57.2). Hence retinal arteriolar narrowing is related to incident renal end points. Narrow arterioles and albuminuria reveal a synergistic predictive value. The findings support a leading role of the microvasculature in the pathogenesis of renal disease progression. They also suggest that retinal photography in combination with albuminuria determination may be useful for risk stratification with respect to renal disease progression in patients with CKD stage 2 to 4.

Description: Objective— Adipocyte fatty acid-binding protein (A-FABP) abundantly expressed in mature adipocytes and activated macrophages has dramatic effects on atherosclerosis in mice. Whether this pathophysiological role of A-FABP may also apply to atherosclerotic disease in humans is still unknown. This study investigated associations among serum A-FABP levels, cardiovascular risk factors, and long-term secondary cardiovascular disease (CVD) outcome in patients with coronary heart disease. Methods and Results— Serum A-FABP levels were measured in 1069 patients with prevalent coronary heart disease and a 10-year prospective follow-up was conducted (median, 119.5 [interquartile range, 74.1–120.6] months). During this period 204 patients (incidence, 24.0/1000 patient-years) experienced a secondary cardiovascular disease event (defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal cerebrovascular stroke). At baseline, circulating A-FABP was positively associated with a cluster of metabolic and inflammatory risk factors and independently predicted the presence of the metabolic syndrome (odds ratio per unit increase of natural log-transformed A-FABP, 2.95; 95% CI, 2.22–3.92, P 〈0.001). On long-term follow-up, subjects with high baseline A-FABP showed an increased risk for secondary cardiovascular disease events (hazard ratio per unit increase, 1.52; 95% CI, 1.18–1.95; P =0.001), which was attenuated after multivariable adjustment (hazard ratio 1.30; 95% CI, 0.98–1.73). In contrast, A-FABP remained significantly associated with cardiovascular death even after multivariable adjustment (hazard ratio, 1.75; 95% CI, 1.17–2.62, P =0.007). Conclusion— Circulating A-FABP levels are associated with long-term prognosis in patients with coronary heart disease and may represent an important pathophysiological mediator of atherosclerosis, which may point to a new target of treatment options.