Longitudinal changes in reproductive hormones through the menopause transition in the Avon Longitudinal Study of Parents and Children (ALSPAC).

We characterised changes in reproductive hormones-LH, FSH, SHBG and AMH-by chronological age and time around the menopause (reproductive age) in mid-life women and explored their associations with lifestyle and reproductive factors. We used data from 1608 women from a UK cohort who had repeat hormone measures and experienced a natural menopause. Multilevel models were used to assess: (i) changes in hormones (outcomes) by reproductive age and chronological age (these age variables being the key exposures) and (ii) associations of body mass index (BMI), smoking, alcohol intake, parity and age at menarche with changes in hormones by reproductive age. Both LH and FSH increased until ~ 5 and 7 years postmenopause, respectively, after which they declined, but not to premenopausal levels. SHBG decreased slightly until ~ 4 years postmenopause and increased thereafter. AMH decreased markedly before menopause and remained low subsequently. For all hormones, the best fitting models included both reproductive and chronological age. BMI, smoking and parity were associated with hormone changes; e.g., higher BMI was associated with slower increase in LH and FSH and decrease in AMH. Reproductive and chronological age contribute to changes in LH, FSH, SHBG and AMH across mid-life in women, and BMI, smoking and parity are associated with these hormone changes.

Vascular Structure and Inflammation in a South African Population: The SABPA Study.

BACKGROUND AND OBJECTIVE: Inflammation plays a role in the early onset of cardiovascular disease. However, longitudinal studies on this topic, especially in South African populations, are scant. We explored whether early changes in vascular structure are associated with changes in inflammation. METHODS: We investigated 303 South African teachers aged 20-65 years at two intervals, three years apart. Standardised methods were used to determine carotid intima-media thickness (IMT) and cross-sectional wall area (CSWA) as measures of vascular structure, as well as the inflammatory markers soluble urokinase plasminogen activator receptor (suPAR), C-reactive protein (CRP) and interleukin-6 (IL-6) at baseline and follow-up. RESULTS: IMT and CSWA were higher, while CRP was lower at follow-up than at baseline. After adjusting for confounding factors, percent change in IMT was inversely associated with percent change in suPAR (ß = -0.12, p = 0.036; adjusted R2 = 0.16) only, and only in the highest tertile of percent change in suPAR (r = -0.31; p = 0.002). CONCLUSION: The early structural changes observed are not related to higher inflammatory levels in this South African population. Future studies are needed to investigate the possible protective effect of suPAR on early changes in vascular structure, especially with the focus on cardiovascular disease prevention.

The novel urinary proteomic classifier HF1 has similar diagnostic and prognostic utility to BNP in heart failure.

AIMS: Measurement of B-type natriuretic peptide (BNP) or N-terminal pro-BNP is recommended as part of the diagnostic workup of patients with suspected heart failure (HF). We evaluated the diagnostic and prognostic utility of the novel urinary proteomic classifier HF1, compared with BNP, in HF. HF1 consists of 85 unique urinary peptide fragments thought, mainly, to reflect collagen turnover. METHODS AND RESULTS: We performed urinary proteome analysis using capillary electrophoresis coupled with mass spectrometry in 829 participants. Of these, 622 had HF (504 had chronic HF and 118 acute HF) and 207 were controls (62 coronary heart disease patients without HF and 145 healthy controls). The area under the receiver operating characteristic (ROC) curve (AUC) using HF1 for the diagnosis of HF (cases vs. controls) was 0.94 (95% CI, 0.92-0.96). This compared with an AUC for BNP of 0.98 (95% CI, 0.97-0.99). Adding HF1 to BNP increased the AUC to 0.99 (0.98-0.99), P < 0.001, and led to a net reclassification improvement of 0.67 (95% CI, 0.54-0.77), P < 0.001. Among 433 HF patients followed up for a median of 989 days, we observed 186 deaths. HF1 had poorer predictive value to BNP for all-cause mortality and did not add prognostic information when combined with BNP. CONCLUSIONS: The urinary proteomic classifier HF1 performed as well, diagnostically, as BNP and provided incremental diagnostic information when added to BNP. HF1 had less prognostic utility than BNP.

Impact of Kidney Function on Cardiovascular Risk and Mortality: A Comparison of South Asian and European Cohorts.

BACKGROUND: Evidence is limited on ethnic differences in associations between kidney function markers and mortality or cardiovascular disease (CVD). METHODS: Baseline cross-sectional analysis and longitudinal follow-up study of a UK population-based cohort of 1,116 Europeans and 1,104 South Asians of predominantly Indian descent, age 52 ± 7 years at baseline (1988-1991). Kidney function was estimated using Cystatin C and creatinine-based chronic kidney disease (CKD) Epidemiology Collaboration estimated glomerular filtration rate (eGFR) equations, and urinary albumin-creatinine ratio (ACR). Mortality was captured at 27 years, and incident CVD at 22 years, from death certification, medical records and participant report. Longitudinal associations between eGFR/ACR and mortality/incident CVD were examined using Cox models. RESULTS: eGFRcys was lower and ACR higher in South Asians than Europeans. eGFRcys and -eGFRcreat were more strongly associated with outcomes in Europeans than South Asians. Conversely, associations between ACR and outcomes were greater in South Asians than Europeans, for example, for CVD mortality: HRs (95% CI) adjusted for CVD risk factors and ACR/eGFRcys as appropriate, p for ethnicity interaction: eGFRcys: Europeans: 0.76 (0.62-0.92), South Asians: 0.92 (0.78-1.07), p = 0.05, eGFRcreat: Europeans 0.81 (0.67-0.99), South Asians 1.18 (0.97-1.41), p = 0.002, ACR: -Europeans: 1.24 (1.08-1.42), South Asians: 1.39 (1.25-1.57), p= 0.23. Addition of all CKD measures to a standard CVD risk factor model modestly improved prediction capability in -Europeans; in South Asians only ACR contributed to improvement. CONCLUSIONS: Strong associations between ACR and outcomes in South Asians of predominantly Indian origin, and null associations for eGFRcys and eGFRcreat, suggest that ACR may have greater utility in CVD risk prediction in South Asians. Further work is needed to validate these -findings.

Early pregnancy soluble E-selectin concentrations and risk of preeclampsia.

OBJECTIVE: Circulating biomarkers of endothelial dysfunction and inflammation are elevated in late pregnancy in women with preeclampsia. We examined plasma levels of inflammatory cytokines and adhesion molecules in early pregnancy, to assess their ability to predict preeclampsia. METHODS: In a prospective longitudinal study, 2600 women with singleton pregnancies and no history of hypertension were recruited at their antenatal hospital (booking) visit at gestational week 12-16. Of these, 49 (1.9%) developed preeclampsia, whereas 74 women matched for age and BMI with uncomplicated pregnancies were selected as controls. A subset of women with risk factors for preeclampsia were sampled again at gestational weeks 16 and 28 (11 cases, 39 controls) and postnatally (six cases, 36 controls). RESULTS: From multiplex analysis, soluble E-selectin concentrations were higher at 12-16 weeks in women who subsequently developed preeclampsia (15.1 ±â€Š4.9 versus 12.9 ±â€Š4.5  ng/ml, P = 0.02). At gestational week 28, E-selectin concentrations were again higher in women who went on to develop preeclampsia compared with controls (14.4 ±â€Š5.6 versus 10.7 ±â€Š3.5  ng/ml, P = 0.010), whereas levels were not different between the two groups in postpartum samples. CONCLUSION: Changes in soluble E-selectin concentration in early pregnancy may reflect underlying pathophysiological processes, potentially providing mechanistic insights into preeclampsia.