There is more female hypertension-related mortality than male. Although women’s blood pressure is lower than men’s in younger life, after menopause the reverse is true. A decrease in estrogen plays a role in women’s midlife increase in blood pressure. However, factors that modify the extent of this increase in individuals are not known. The renin-angiotensin-aldosterone system (RAAS) is crucial to blood pressure regulation, and it is also the target of many antihypertensive medications. These different medications vary in their effects, depending on where in the RAAS they act. Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) do not reliably prevent the production of aldosterone, which can “break through” these treatments, worsening outcomes. We propose to study changes in serum aldosterone levels in 1,534 women participating in a large, longitudinal study of women’s midlife health, the Study of Women’s Heath Across the Nation (SWAN). These measurements will be made in sera collected 5±1 years prior to the final menstrual period (FMP), within a year of the FMP, and 5±1 years after the FMP. In addition, since renin measurements can help provide context to aldosterone measurements, we will also measure plasma renin concentration when matching plasma samples are available. The broad, long-term objective of the project is to improve cardiovascular health in midlife and older women. The project has 3 Specific Aims. Aim 1 is to identify the effect of the menopausal transition on the relationship between aldosterone and changes in blood pressure. We will leverage the SWAN study to identify how high serum aldosterone concentration is associated with time-averaged blood pressure during the menopausal transition. Aim 2 is to identify the impact of aldosterone breakthrough on blood pressure outcomes across the menopausal transition. We will identify women whose initial (FMP -5 years) aldosterone measurement is in the absence of an ACEi or ARB and in whom a subsequent aldosterone measurement was under treatment with one of these drugs. We will identify the impact of aldosterone breakthrough on systolic blood pressure. Aim 3 is to identify the effect of changes in aldosterone during the menopausal transition on long-term renal and cardiovascular outcomes. We will identify the relationship between serum aldosterone concentration and subsequent incident cardiovascular events. When our study is complete, we will disseminate for the first time an understanding of the changes in aldosterone and renin during menopause, medication effects on these hormones, and the influence of these hormones on cardiovascular outcomes.