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1.  Adult height and the risk of cause-specific death and vascular morbidity in 1 million people: individual participant meta-analysis 
Wormser, David | Angelantonio, Emanuele Di | Kaptoge, Stephen | Wood, Angela M | Gao, Pei | Sun, Qi | Walldius, Göran | Selmer, Randi | Verschuren, WM Monique | Bueno-de-Mesquita, H Bas | Engström, Gunnar | Ridker, Paul M | Njølstad, Inger | Iso, Hiroyasu | Holme, Ingar | Giampaoli, Simona | Tunstall-Pedoe, Hugh | Gaziano, J Michael | Brunner, Eric | Kee, Frank | Tosetto, Alberto | Meisinger, Christa | Brenner, Hermann | Ducimetiere, Pierre | Whincup, Peter H | Tipping, Robert W | Ford, Ian | Cremer, Peter | Hofman, Albert | Wilhelmsen, Lars | Clarke, Robert | de Boer, Ian H | Jukema, J Wouter | Ibañez, Alejandro Marín | Lawlor, Debbie A | D'Agostino, Ralph B | Rodriguez, Beatriz | Casiglia, Edoardo | Stehouwer, Coen DA | Simons, Leon A | Nietert, Paul J | Barrett-Connor, Elizabeth | Panagiotakos, Demosthenes B | Björkelund, Cecilia | Strandberg, Timo E | Wassertheil-Smoller, Sylvia | Blazer, Dan G | Meade, Tom W | Welin, Lennart | Svärdsudd, Kurt | Woodward, Mark | Nissinen, Aulikki | Kromhout, Daan | Jørgensen, Torben | Tilvis, Reijo S | Guralnik, Jack M | Rosengren, Annika | Taylor, James O | Kiechl, Stefan | Dagenais, Gilles R | Gerry, F | Fowkes, R | Wallace, Robert B | Khaw, Kay-Tee | Shaffer, Jonathan A | Visser, Marjolein | Kauhanen, Jussi | Salonen, Jukka T | Gallacher, John | Ben-Shlomo, Yoav | Kitamura, Akihiko | Sundström, Johan | Wennberg, Patrik | Kiyohara, Yutaka | Daimon, Makoto | de la Cámara, Agustin Gómez | Cooper, Jackie A | Onat, Altan | Devereux, Richard | Mukamal, Kenneth J | Dankner, Rachel | Knuiman, Matthew W | Crespo, Carlos J | Gansevoort, Ron T | Goldbourt, Uri | Nordestgaard, Børge G | Shaw, Jonathan E | Mussolino, Michael | Nakagawa, Hidaeki | Fletcher, Astrid | Kuller, Lewis H | Gillum, Richard F | Gudnason, Vilmundur | Assmann, Gerd | Wald, Nicholas | Jousilahti, Pekka R | Greenland, Philip | Trevisan, Maurizio | Ulmer, Hanno | Butterworth, Adam S | Folsom, Aaron R | Davey-Smith, George | Hu, Frank B | Danesh, John | Tipping, Robert W | Ford, Charles E | Simpson, Lara M | Walldius, Göran | Jungner, Ingmar | Folsom, Aaron R | Demerath, Ellen W | Franceschini, Nora | Lutsey, Pamela L | Panagiotakos, Demosthenes B | Pitsavos, Christos | Chrysohoou, Christina | Stefanadis, Christodoulos | Shaw, Jonathan E | Atkins, Robert | Zimmet, Paul Z | Barr, Elizabeth LM | Knuiman, Matthew W | Whincup, Peter H | Wannamethee, S Goya | Morris, Richard W | Willeit, Johann | Kiechl, Stefan | Weger, Siegfried | Oberhollenzer, Friedrich | Wald, Nicholas | Ebrahim, Shah | Lawlor, Debbie A | Gallacher, John | Ben-Shlomo, Yoav | Yarnell, John WG | Casiglia, Edoardo | Tikhonoff, Valérie | Greenland, Philip | Shay, Christina M | Garside, Daniel B | Nietert, Paul J | Sutherland, Susan E | Bachman, David L | Keil, Julian E | de Boer, Ian H | Kizer, Jorge R | Psaty, Bruce M | Mukamal, Kenneth J | Nordestgaard, Børge G | Tybjærg-Hansen, Anne | Jensen, Gorm B | Schnohr, Peter | Giampaoli, Simona | Palmieri, Luigi | Panico, Salvatore | Pilotto, Lorenza | Vanuzzo, Diego | de la Cámara, Agustin Gómez | Simons, Leon A | Simons, Judith | McCallum, John | Friedlander, Yechiel | Gerry, F | Fowkes, R | Price, Jackie F | Lee, Amanda J | Taylor, James O | Guralnik, Jack M | Phillips, Caroline L | Wallace, Robert B | Kohout, Frank J | Cornoni-Huntley, Joan C | Guralnik, Jack M | Blazer, Dan G | Guralnik, Jack M | Phillips, Caroline L | Phillips, Caroline L | Guralnik, Jack M | Khaw, Kay-Tee | Wareham, Nicholas J | Brenner, Hermann | Schöttker, Ben | Müller, Heiko | Rothenbacher, Dietrich | Wennberg, Patrik | Jansson, Jan-Håkan | Nissinen, Aulikki | Donfrancesco, Chiara | Giampaoli, Simona | Woodward, Mark | Vartiainen, Erkki | Jousilahti, Pekka R | Harald, Kennet | Salomaa, Veikko | D'Agostino, Ralph B | Vasan, Ramachandran S | Fox, Caroline S | Pencina, Michael J | Daimon, Makoto | Oizumi, Toshihide | Kayama, Takamasa | Kato, Takeo | Bladbjerg, Else-Marie | Jørgensen, Torben | Møller, Lars | Jespersen, Jørgen | Dankner, Rachel | Chetrit, Angela | Lubin, Flora | Svärdsudd, Kurt | Eriksson, Henry | Welin, Lennart | Lappas, Georgios | Rosengren, Annika | Lappas, Georgios | Welin, Lennart | Svärdsudd, Kurt | Eriksson, Henry | Lappas, Georgios | Bengtsson, Calle | Lissner, Lauren | Björkelund, Cecilia | Cremer, Peter | Nagel, Dorothea | Strandberg, Timo E | Salomaa, Veikko | Tilvis, Reijo S | Miettinen, Tatu A | Tilvis, Reijo S | Strandberg, Timo E | Kiyohara, Yutaka | Arima, Hisatomi | Doi, Yasufumi | Ninomiya, Toshiharu | Rodriguez, Beatriz | Dekker, Jacqueline M | Nijpels, Giel | Stehouwer, Coen DA | Hu, Frank B | Sun, Qi | Rimm, Eric B | Willett, Walter C | Iso, Hiroyasu | Kitamura, Akihiko | Yamagishi, Kazumasa | Noda, Hiroyuki | Goldbourt, Uri | Vartiainen, Erkki | Jousilahti, Pekka R | Harald, Kennet | Salomaa, Veikko | Kauhanen, Jussi | Salonen, Jukka T | Kurl, Sudhir | Tuomainen, Tomi-Pekka | Poppelaars, Jan L | Deeg, Dorly JH | Visser, Marjolein | Meade, Tom W | De Stavola, Bianca Lucia | Hedblad, Bo | Nilsson, Peter | Engström, Gunnar | Verschuren, WM Monique | Blokstra, Anneke | de Boer, Ian H | Shea, Steven J | Meisinger, Christa | Thorand, Barbara | Koenig, Wolfgang | Döring, Angela | Verschuren, WM Monique | Blokstra, Anneke | Bueno-de-Mesquita, H Bas | Wilhelmsen, Lars | Rosengren, Annika | Lappas, Georgios | Fletcher, Astrid | Nitsch, Dorothea | Kuller, Lewis H | Grandits, Greg | Tverdal, Aage | Selmer, Randi | Nystad, Wenche | Mussolino, Michael | Gillum, Richard F | Hu, Frank B | Sun, Qi | Manson, JoAnn E | Rimm, Eric B | Hankinson, Susan E | Meade, Tom W | De Stavola, Bianca Lucia | Cooper, Jackie A | Bauer, Kenneth A | Davidson, Karina W | Kirkland, Susan | Shaffer, Jonathan A | Shimbo, Daichi | Kitamura, Akihiko | Iso, Hiroyasu | Sato, Shinichi | Holme, Ingar | Selmer, Randi | Tverdal, Aage | Nystad, Wenche | Nakagawa, Hidaeki | Miura, Katsuyuki | Sakurai, Masaru | Ducimetiere, Pierre | Jouven, Xavier | Bakker, Stephan JL | Gansevoort, Ron T | van der Harst, Pim | Hillege, Hans L | Crespo, Carlos J | Garcia-Palmieri, Mario R | Kee, Frank | Amouyel, Philippe | Arveiler, Dominique | Ferrières, Jean | Schulte, Helmut | Assmann, Gerd | Jukema, J Wouter | de Craen, Anton JM | Sattar, Naveed | Stott, David J | Cantin, Bernard | Lamarche, Benoît | Després, Jean-Pierre | Dagenais, Gilles R | Barrett-Connor, Elizabeth | Bergstrom, Jaclyn | Bettencourt, Richele R | Buisson, Catherine | Gudnason, Vilmundur | Aspelund, Thor | Sigurdsson, Gunnar | Thorsson, Bolli | Trevisan, Maurizio | Hofman, Albert | Ikram, M Arfan | Tiemeier, Henning | Witteman, Jacqueline CM | Tunstall-Pedoe, Hugh | Tavendale, Roger | Lowe, Gordon DO | Woodward, Mark | Devereux, Richard | Yeh, Jeun-Liang | Ali, Tauqeer | Calhoun, Darren | Ben-Shlomo, Yoav | Davey-Smith, George | Onat, Altan | Can, Günay | Nakagawa, Hidaeki | Sakurai, Masaru | Nakamura, Koshi | Morikawa, Yuko | Njølstad, Inger | Mathiesen, Ellisiv B | Løchen, Maja-Lisa | Wilsgaard, Tom | Sundström, Johan | Ingelsson, Erik | Michaëlsson, Karl | Cederholm, Tommy | Gaziano, J Michael | Buring, Julie | Ridker, Paul M | Gaziano, J Michael | Ridker, Paul M | Ulmer, Hanno | Diem, Günter | Concin, Hans | Rodeghiero, Francesco | Tosetto, Alberto | Wassertheil-Smoller, Sylvia | Manson, JoAnn E | Marmot, Michael | Clarke, Robert | Fletcher, Astrid | Brunner, Eric | Shipley, Martin | Kivimaki, Mika | Ridker, Paul M | Buring, Julie | Ford, Ian | Robertson, Michele | Ibañez, Alejandro Marín | Feskens, Edith | Geleijnse, Johanna M | Kromhout, Daan | Walker, Matthew | Watson, Sarah | Alexander, Myriam | Butterworth, Adam S | Angelantonio, Emanuele Di | Franco, Oscar H | Gao, Pei | Gobin, Reeta | Haycock, Philip | Kaptoge, Stephen | Seshasai, Sreenivasa R Kondapally | Lewington, Sarah | Pennells, Lisa | Rapsomaniki, Eleni | Sarwar, Nadeem | Thompson, Alexander | Thompson, Simon G | Walker, Matthew | Watson, Sarah | White, Ian R | Wood, Angela M | Wormser, David | Zhao, Xiaohui | Danesh, John
Background The extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.
Methods We calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual–participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies.
Results For people born between 1900 and 1960, mean adult height increased 0.5–1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96–0.99) for death from any cause, 0.94 (0.93–0.96) for death from vascular causes, 1.04 (1.03–1.06) for death from cancer and 0.92 (0.90–0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12–1.42) for risk of melanoma death to 0.84 (0.80–0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.
Conclusion Adult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
doi:10.1093/ije/dys086
PMCID: PMC3465767  PMID: 22825588
Height; cardiovascular disease; cancer; cause-specific mortality; epidemiological study; meta-analysis
2.  Depression and quality of life before and after breast cancer diagnosis in older women from the Women's Health Initiative 
Purpose
Distress and reduced quality of life (QOL) are common among people with cancer. No study has compared these variables after breast cancer diagnosis to pre-cancer diagnosis levels.
Methods
Data on women with breast cancer 50 years of age or older (n=6949) were analyzed from the Women's Health Initiative (1993-2013). Health-related QOL (physical function, mental health) was measured using Rand-36. Depressive symptoms were measured with the 6-item Center for Epidemiologic Studies Depression. Assessments occurred before and after the cancer diagnosis. Hierarchical linear modeling compared pre-cancer QOL and depressive symptoms to levels post-diagnosis and tested whether pre-cancer physical activity, stressful life events, sleep disturbance, and pain predicted post-diagnosis outcomes.
Results
Compared with pre-cancer levels, depressive symptoms increased (20.0% increase at 0-6 months, 12.9% increase at 6-12 months), while physical function (−3.882 points at 0-6 months, −3.545 at 6-12 months) and mental health decreased (−2.899 points at 0-6 months, −1.672 at 6-12 months) in the first year after diagnosis (p's<.01). Depressive symptoms returned to pre-cancer levels after 10 years but QOL remained significantly lower. At more than 10 years post-diagnosis, physical function was 2.379 points lower than pre-cancer levels (p<0.01) while mental health was 1.922 points lower (p<0.01). All pre-cancer predictors were associated with all outcomes. Pain predicted uniquely greater decreases in physical function post-diagnosis.
Conclusions
Depressive symptoms increased and QOL decreased following breast cancer diagnosis compared with pre-cancer levels, particularly in the first year.
Implications for Cancer Survivors
QOL may remain lower for years after breast cancer diagnosis, though decreases are small.
doi:10.1007/s11764-015-0438-y
PMCID: PMC4547920  PMID: 25708515
breast cancer; neoplasm; depression; distress; health-related quality of life; women's health
3.  Factors Associated with Nursing Home Admission after Stroke in Older Women 
Objective
We examined the social and economic factors associated with nursing home (NH) admission in older women, overall and post-stroke.
Methods
The Women’s Health Initiative (WHI) included women aged 50–79 years at enrollment (1993–1998). In the WHI Extension Study (2005–2010), participants annually reported any NH admission in the preceding year. Separate multivariate logistic regression models analyzed social and economic factors associated with long-term NH admission, defined as an admission on two or more questionnaires, overall and post-stroke.
Results
Of 103,237 participants, 8,904 (8.6%) reported NH admission (2005–2010); 534 of 2,225 (24.0%) women with incident stroke reported post-stroke NH admission. Decreased likelihoods of NH admission overall were demonstrated for Asian, Black and Hispanic women (versus whites, aORs=0.35–0.44, p<.001) and women with higher income (aOR= 0.75, 95%CI=0.63–0.90); while increased likelihoods of NH admission overall were seen for women with lower social support (aOR=1.34, 95%CI=1.16–1.54) and with incident stroke (aOR=2.59, 95%CI=2.15–3.12). Increased odds of NH admission after stroke were demonstrated for women with moderate disability after stroke (aOR=2.76, 95%CI=1.73–4.42). Further adjustment for stroke severity eliminated the association found for race/ethnicity, income and social support.
Conclusion
The level of care needed after a disabling stroke may overwhelm social and economic structures in place that might otherwise enable avoidance of nursing home admission. We need to identify ways to provide care consistent with patients’ preferences, even after a disabling stroke.
doi:10.1016/j.jstrokecerebrovasdis.2015.06.013
PMCID: PMC4592792  PMID: 26169547
disability; institutionalization; race; ethnicity; social support; long-term care
4.  Mental Health and Exposure to the United States: Key Correlates from the Hispanic Community Health Study of Latinos 
We examined the association between exposure to the U.S. and symptoms of poor mental health among adult Hispanic/Latinos (N=15,004) overall and by Hispanic/Latino background. Using data from the Hispanic Community Health Study of Latinos (HCHS/SOL), we estimated logistic regressions to model the risk of moderate to severe symptoms of psychological distress, depression, and anxiety as a function of years in the U.S. and 6 key psychosocial risk and protective factors. In unadjusted models, increased time in the U.S. was associated with higher risk of poor mental health. After adjustment for just 3 key factors – perceived discrimination, perceived U.S. social standing, and the size of close social networks, differences in the odds of poor mental health by years in the U.S became insignificant for Hispanics/Latinos overall. However, analyses by Hispanic/Latino background revealed different patterns of association with exposure to the U.S. that could not be fully explained.
doi:10.1097/NMD.0000000000000350
PMCID: PMC4552578  PMID: 26237134
Latino; Hispanic; Immigrant; depression; anxiety; acculturation
5.  Circulating Adipokines and Inflammatory Markers and Postmenopausal Breast Cancer Risk 
Background:
Adipokines and inflammation may provide a mechanistic link between obesity and postmenopausal breast cancer, yet epidemiologic data on their associations with breast cancer risk are limited.
Methods:
In a case-cohort analysis nested within the Women’s Health Initiative Observational Study, a prospective cohort of postmenopausal women, baseline plasma samples from 875 incident breast cancer case patients and 839 subcohort participants were tested for levels of seven adipokines, namely leptin, adiponectin, resistin, interleukin-6, tumor necrosis factor-α, hepatocyte growth factor, and plasminogen activator inhibitor-1, and for C-reactive protein (CRP), an inflammatory marker. Data were analyzed by multivariable Cox modeling that included established breast cancer risk factors and previously measured estradiol and insulin levels. All statistical tests were two-sided.
Results:
The association between plasma CRP levels and breast cancer risk was dependent on hormone therapy (HT) use at baseline (P interaction = .003). In a model that controlled for multiple breast cancer risk factors including body mass index (BMI), estradiol, and insulin, CRP level was positively associated with breast cancer risk among HT nonusers (hazard ratio for high vs low CRP levels = 1.67, 95% confidence interval = 1.04 to 2.68, P trend = .029). None of the other adipokines were statistically significantly associated with breast cancer risk. Following inclusion of CRP, insulin, and estradiol in a multivariable model, the association of BMI with breast cancer was attenuated by 115%.
Conclusion:
These data indicate that CRP is a risk factor for postmenopausal breast cancer among HT nonusers. Inflammatory mediators, together with insulin and estrogen, may play a role in the obesity–breast cancer relation.
doi:10.1093/jnci/djv169
PMCID: PMC4651104  PMID: 26185195
6.  Prevalence of Low Cardiovascular Risk Profile Among Diverse Hispanic/Latino Adults in the United States by Age, Sex, and Level of Acculturation: The Hispanic Community Health Study/Study of Latinos 
Background
Favorable levels of all readily measurable major cardiovascular disease risk factors (ie, low risk [LR]) are associated with lower risks of cardiovascular disease morbidity and mortality. Data are not available on LR prevalence among Hispanic/Latino adults of diverse ethnic backgrounds. This study aimed to describe the prevalence of a low cardiovascular disease risk profile among Hispanic/Latino adults in the United States and to examine cross‐sectional associations of LR with measures of acculturation.
Methods and Results
The multicenter, prospective, population‐based Hispanic Community Health Study/Study of Latinos examined 16 415 men and women aged 18 to 74 years at baseline (2008–2011) with diverse Hispanic/Latino backgrounds. Analyses involved 14 757 adults (mean age 41.3 years; 60.6% women). LR was defined using national guidelines for favorable levels of serum cholesterol, blood pressure, and body mass index and by not having diabetes mellitus and not currently smoking. Age‐adjusted LR prevalence was low (8.4% overall; 5.1% for men, 11.2% for women) and varied by background (4.2% in men of Mexican heritage versus 15.0% in women of Cuban heritage). Lower acculturation (assessed using proxy measures) was significantly associated with higher odds of a LR profile among women only: Age‐adjusted odds ratios of having LR were 1.64 (95% CI 1.24–2.17) for foreign‐born versus US‐born women and 1.96 (95% CI 1.49–2.58) for women residing in the United States <10 versus ≥10 years.
Conclusions
Among diverse US Hispanic/Latino adults, the prevalence of a LR profile is low. Lower acculturation is associated with higher odds of a LR profile among women but not men. Comprehensive public health strategies are needed to improve the cardiovascular health of US Hispanic/Latino adults.
doi:10.1161/JAHA.116.003929
PMCID: PMC5015308  PMID: 27543802
cardiovascular disease prevention; cardiovascular disease risk factors; low risk; Primary Prevention; Cardiovascular Disease; Race and Ethnicity; Risk Factors
7.  Association of Baseline Depressive Symptoms with Prevalent and Incident Pre-Hypertension and Hypertension in Postmenopausal Hispanic Women: Results from the Women’s Health Initiative 
PLoS ONE  2016;11(4):e0152765.
Background
Depression and depressive symptoms are risk factors for hypertension (HTN) and cardiovascular disease (CVD). Hispanic women have higher rates of depressive symptoms compared to other racial/ethnic groups yet few studies have investigated its association with incident prehypertension and hypertension among postmenopausal Hispanic women. This study aims to assess if an association exists between baseline depression and incident hypertension at 3 years follow-up among postmenopausal Hispanic women.
Methods
Prospective cohort study, Women’s Health Initiative (WHI), included 4,680 Hispanic women who participated in the observational and clinical trial studies at baseline and at third-year follow-up. Baseline current depressive symptoms and past depression history were measured as well as important correlates of depression—social support, optimism, life events and caregiving. Multinomial logistic regression was used to estimate prevalent and incident prehypertension and hypertension in relation to depressive symptoms.
Results
Prevalence of current baseline depression ranged from 26% to 28% by hypertension category and education moderated these rates. In age-adjusted models, women with depression were more likely to be hypertensive (OR = 1.25; 95% CI 1.04–1.51), although results were attenuated when adjusting for covariates. Depression at baseline in normotensive Hispanic women was associated with incident hypertension at year 3 follow-up (OR = 1.74; 95% CI 1.10–2.74) after adjustment for insurance and behavioral factors. However, further adjustment for clinical covariates attenuated the association. Analyses of psychosocial variables correlated with depression but did not alter findings. Low rates of antidepressant medication usage were also reported.
Conclusions
In the largest longitudinal study to date of older Hispanic women which included physiologic, behavioral and psychosocial moderators of depression, there was no association between baseline depressive symptoms and prevalent nor incident pre-hypertension and hypertension. We found low rates of antidepressant medication usage among Hispanic women suggesting a possible point for clinical intervention.
Trial Registration
Clinicaltrials.gov NCT00000611
doi:10.1371/journal.pone.0152765
PMCID: PMC4849764  PMID: 27124184
8.  Sleep Apnea is Independently Associated with Peripheral Arterial Disease in the Hispanic Community Health Study/Study of Latinos 
Objective
Sleep apnea (SA) has been linked with various forms of cardiovascular disease, but little is known about its association with peripheral artery disease (PAD) measured using the ankle- brachial index (ABI). This relationship was evaluated in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).
Approach and Results
We studied 8,367 HCHS/SOL participants who were 45 to 74 years of age. Sleep symptoms were examined with the self-reported Sleep Health Questionnaire. SA was assessed using an in-home sleep study. Systolic blood pressure was measured in all extremities to compute the ABI. PAD was defined as ABI < 0.90 in either leg. Multivariable logistic regression was utilized to investigate the association between moderate-to-severe SA, defined as apnea-hypopnea index (AHI) ≥15, and the presence of PAD. Analyses were adjusted for covariates.
The prevalence of PAD was 4.7% (n=390). The mean AHI was significantly higher among adults with PAD compared to those without (11.1 vs. 8.6 events/hour, p=0.046). After adjusting for covariates, moderate-to-severe SA was associated with a 70% increase in the odds of PAD (odds ratio 1.7, 95% CI: 1.1 – 2.5, p=0.0152). This association was not modified by sex (p=0.8739). However, there was evidence that the association between moderate-to-severe SA and PAD varied by Hispanic/Latino background (p < 0.01). Specifically, the odds were stronger in Mexican (adjusted OR 2.9, 95% CI: 1.3, 6.2) and in Puerto Rican Americans (adjusted OR 2.0, 95% CI: 0.97 – 4.2) than in other backgrounds.
Conclusions
Moderate-to-severe SA is associated with higher odds of PAD in Hispanic/Latino adults.
doi:10.1161/ATVBAHA.114.304625
PMCID: PMC4545273  PMID: 25657310
Sleep apnea; peripheral arterial disease; ankle-brachial index; subclinical atherosclerosis; US Hispanics and Latinos
9.  Folate, Vitamin B6 and Vitamin B12 Intake and Mild Cognitive Impairment and Probable Dementia in the Women’s Health Initiative Memory Study 
Background
Whether higher B vitamin (B6, B12, and folate) intake is protective against cognitive decline in later life remains uncertain. Several prospective, observational studies find higher B vitamin intake to be associated with lower risk of dementia; other studies, including most trials of B vitamin supplementation, observe no effect on cognition. We examine this question in a large population of older women carefully monitored for development of mild cognitive impairment (MCI) and probable dementia.
Objective
To determine whether baseline folate, vitamin B6 and/or B12 intake, alone or in combination, are associated with incident MCI/probable dementia among older women.
Design
Prospective, longitudinal cohort study. B vitamin intake was self-reported using a food frequency questionnaire administered at baseline between May 1996 and December 1999.
Participants/Setting
Postmenopausal women (n=7,030) free of MCI/probable dementia at baseline in the Women’s Health Initiative Memory Study.
Main outcome measures
Over a mean follow-up of 5.0 years, 238 cases of incident MCI and 69 cases of probable dementia were identified through rigorous screening and expert adjudication.
Statistical analyses
Cox proportional hazard models adjusting for sociodemographic and lifestyle factors examined the association of B vitamin intake above and below the recommended daily allowance and incident MCI/probable dementia.
Results
Folate intake below the RDA at study baseline was associated with increased risk of incident MCI/probable dementia (HR=2.0, 95% CI: 1.3, 2.9), after controlling for multiple confounders. There were no significant associations between vitamins B6 or B12 and MCI/probable dementia, nor any evidence of an interaction between these vitamins and folate intake.
Conclusions
Folate intake below the RDA may increase risk for MCI/probable dementia in later life. Future research should include long-term trials of folic acid supplementation to examine whether folate may impart a protective effect on cognition in later life.
doi:10.1016/j.jand.2014.07.006
PMCID: PMC4312724  PMID: 25201007
Folic acid; vitamin B12; vitamin B6; dementia; cognitive impairment; women’s health; aging
10.  Weight Change, Psychological Well-Being, and Vitality in Adults Participating in a Cognitive-Behavioral Weight Loss Program 
Objective
Excess weight has been associated with numerous psychological problems, including depression and anxiety. This study examined the impact of intentional weight loss on the psychological well-being of adults participating in three clinical weight loss interventions.
Methods
This population consisted of 588 overweight or obese individuals randomized into one of three weight loss interventions of incremental intensity for twelve months. Psychological well-being was measured at baseline, six, and twelve months using the Psychological Well-Being Index.
Results
Mean weight loss was 5.0 pounds at twelve months. Weight change at twelve months was associated with higher overall psychological well-being (r = −.20, p < .001), lower levels of anxiety (r = −.16, p = .001) and depression (r =−.13, p = .004), and higher positive well being (r = −.19, p < .001), self control (r = −.13, p = .004), and vitality (r = −.22, p < .001). Vitality was found to be the best predictor of weight change at twelve months (p < .001).
Conclusions
Weight loss was associated with positive changes in psychological well-being. Increased vitality contributed the largest percentage of variance to this change.
doi:10.1037/a0029186
PMCID: PMC4733266  PMID: 22888821
psychological well-being; weight loss; vitality; obesity
11.  Breast Cancer Risk in Metabolically Healthy but Overweight Postmenopausal Women 
Cancer research  2015;75(2):270-274.
Adiposity is an established risk factor for postmenopausal breast cancer. Recent data suggest that high insulin levels in overweight women may play a major role in this relationship, due to insulin’s mitogenic/anti-apoptotic activity. However, whether overweight women who are metabolically healthy (i.e. normal insulin sensitivity) have elevated risk of breast cancer is unknown. We investigated whether overweight women with normal insulin sensitivity (i.e., homeostasis model assessment of insulin resistance [HOMA-IR] index, or fasting insulin level, within the lowest quartile [q1]) have increased breast cancer risk. Subjects were incident breast cancer cases (N=497) and a subcohort (N=2,830) of Women’s Health Initiative (WHI) participants with available fasting insulin and glucose levels. In multivariate Cox models, metabolically healthy overweight women, defined using HOMA-IR, were not at elevated risk of breast cancer compared to metabolically healthy normal weight women (hazard ratio [HR]HOMA-IR=0.96; 95% confidence interval [CI],0.64-1.42). In contrast, the risk among women with high (q3-4) HOMA-IRs was elevated whether they were overweight (HRHOMA-IR=1.76; 95% CI,1.19-2.60) or normal weight (HRHOMA-IR=1.80; 95% CI,0.88-3.70). Similarly, using fasting insulin to define metabolic health, metabolically unhealthy women (insulin q3-4) were at higher risk of breast cancer regardless of whether they were normal weight (HRinsulin=2.06; 95% CI,1.01-4.22) or overweight (HRinsulin=2.01; 95% CI,1.35-2.99), whereas metabolically healthy overweight women did not have significantly increased risk of breast cancer (HRinsulin=0.96; 95% CI,0.64-1.42) relative to metabolically healthy normal weight women. Metabolic health (e.g., HOMA-IR or fasting insulin) may be more biologically relevant and more useful for breast cancer risk stratification, than adiposity per se.
doi:10.1158/0008-5472.CAN-14-2317
PMCID: PMC4657855  PMID: 25593034
12.  Dyslipidemia Patterns among Hispanics/Latinos in the United States of Diverse Background 
The American journal of medicine  2014;127(12):1186-94.e1.
Background
The prevalence and determinants of dyslipidemia patterns among Hispanics/Latinos are not well known.
Methods
Lipid and lipoprotein data were used from the Hispanic Community Health Study / Study of Latinos -- a population-based cohort of 16,415 US Hispanic/Latinos ages 18–74. National Cholesterol Education Program cutoffs were employed. Differences in demographics, lifestyle factors, biological and acculturation characteristics were compared among those with and without dyslipidemia.
Results
Mean age was 41.1 years and 47.9% were male. The overall prevalence of any dyslipidemia was 65.0%. The prevalence of elevated LDL-C was 36.0% and highest among Cubans (44.5%; p<0.001). Low HDL-C was present in 41.4% and did not significantly differ across Hispanic background groups (p=0.09). High triglycerides were seen in 14.8% of Hispanics/Latinos, most commonly among Central Americans (18.3%; p<0.001). Elevated non-HDL-C was seen in 34.7% with the highest prevalence among Cubans (43.3%; p<0.001). Dominicans consistently had a lower prevalence of most types of dyslipidemia. In multivariate analyses, the presence of any dyslipidemia was associated with increasing age, body mass index and low physical activity. Older age, female gender, diabetes, low physical activity, and alcohol use were associated with specific dyslipidemia types. Spanish-language preference and lower educational status were associated with higher dyslipidemia prevalence.
Conclusion
Dyslipidemia is highly prevalent among US Hispanics/Latinos; Cubans seem particularly at risk. Determinants of dyslipidemia varied across Hispanic backgrounds with socioeconomic status and acculturation having a significant effect on dyslipidemia prevalence. This information can help guide public health measures to prevent disparities among the US Hispanic/Latino population.
doi:10.1016/j.amjmed.2014.07.026
PMCID: PMC4551715  PMID: 25195188
Lipids; Dyslipidemia; Hispanics; Race-ethnic; Epidemiology
13.  Mammography Interval and Breast Cancer Mortality in Women over the age of 75 
Purpose
To evaluate the relationship between mammography interval and breast cancer mortality among older women with breast cancer.
Methods
The study population included 1,914 women diagnosed with invasive breast cancer at age 75 or later during their participation in the Women’s Health Initiative, with an average follow-up of 4.4 years (3.1 SD). Cause of death was based on medical record review. Mammography interval was defined as the time between the last self-reported mammogram 7 or more months prior to diagnosis, and the date of diagnosis. Multivariable adjusted hazards ratios (HR) and 95% confidence intervals (CIs) for breast cancer mortality and all-cause mortality were computed from Cox proportional hazards analyses.
Results
Prior mammograms were reported by 73.0 % of women from 7 months to ≤ 2 year of diagnosis (referent group), 19.4% (> 2 – < 5 years), and 7.5% (≥5 years or no prior mammogram). Women with the longest vs. shortest intervals, had more poorly differentiated (28.5% vs. 22.7%), advanced stage (25.7% vs. 22.9%) and estrogen receptor negative tumors (20.9% vs. 13.1%). Compared to the referent group, women with intervals of > 2 – < 5 years or ≥ 5 years had an increased risk of breast cancer mortality (hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.03–2.54) and (HR 2.80, 95% CI, 1.57–5.00) respectively, p trend = 0.0002. There was no significant relationship between mammography interval and other causes of death.
Conclusions
These results suggest a continued role for screening mammography among women 75 years of age and older.
doi:10.1007/s10549-014-3114-4
PMCID: PMC4278588  PMID: 25261290
14.  Depression, anxiety, antidepressant use, and cardiovascular disease among Hispanic men and women of different national backgrounds: results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) 
Annals of epidemiology  2014;24(11):822-830.
Purpose
Describe prevalence and relationships to cardiovascular morbidity of depression, anxiety and medication use among Hispanic/Latinos of different ethnic backgrounds.
Methods
Cross-sectional analysis of 15,864 men and women ages 18–74 in the population-based Hispanic Community Health Study/Study of Latinos. Depressive and anxiety symptoms were assessed with shortened Center for Epidemiological Studies Depression scale and Spielberger Trait Anxiety Scale.
Results
Prevalence of high depressive symptoms ranged from low of 22.3% (95%CI: 20.4–24.3) to high of 38.0% (95%CI: 35.2–41.0) among those of Mexican or Puerto Rican background respectively. Adjusted odds ratios for depression rose monotonically with number of CVD risk factors from 1.46 (95%CI: 1.18, 1.75) for those with no risk factors to 4.36 (95%CI: 2.47, 7.70) for those with 5 risk factors. Antidepressant medication was used by 5% with striking differences between those with and without history of CVD (15.4% and 4.6% respectively) and between insured (8.2%) and uninsured (1.8%).
Conclusions
Among US Hispanics/Latinos, high depression and anxiety symptoms varied nearly twofold by Hispanic background and sex, history of CVD and increasing number of CVD risk factors. Antidepressant medication use was lower than in the general population, suggesting under treatment especially among those who had no health insurance.
doi:10.1016/j.annepidem.2014.09.003
PMCID: PMC4281495  PMID: 25439033
depression; anxiety; Hispanics; Latinos; ethnic differences; antidepressants; antianxiety medications; HCHS/SOL; cardiovascular risk
15.  THE EFFECT OF HORMONE THERAPY ON MEAN BLOOD PRESSURE AND VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY IN POSTMENOPAUSAL WOMEN: RESULTS FROM THE WOMEN’S HEALTH INITIATIVE RANDOMIZED CONTROLLED TRIALS 
Journal of hypertension  2014;32(10):2071-2081.
Objectives
Mean and visit-to-visit variability (VVV) of blood pressure are associated with an increased cardiovascular disease risk. We examined the effect of hormone therapy on mean and VVV of blood pressure in postmenopausal women from the Women’s Health Initiative (WHI) randomized controlled trials.
Methods
Blood pressure was measured at baseline and annually in the two WHI hormone therapy trials in which 10,739 and 16,608 postmenopausal women were randomized to conjugated equine estrogens (CEE, 0.625 mg/day) or placebo, and CEE plus medroxyprogesterone acetate (MPA, 2.5 mg/day) or placebo, respectively.
Results
At the first annual visit (Year 1), mean systolic blood pressure was 1.04 mmHg (95% CI 0.58, 1.50) and 1.35 mmHg (95% CI 0.99, 1.72) higher in the CEE and CEE+MPA arms respectively compared to corresponding placebos. These effects remained stable after Year 1. CEE also increased VVV of systolic blood pressure (ratio of VVV in CEE vs. placebo, 1.03, P<0.001), whereas CEE+MPA did not (ratio of VVV in CEE+MPA vs. placebo, 1.01, P=0.20). After accounting for study drug adherence, the effects of CEE and CEE+MPA on mean systolic blood pressure increased at Year 1, and the differences in the CEE and CEE+MPA arms vs. placebos also continued to increase after Year 1. Further, both CEE and CEE+MPA significantly increased VVV of systolic blood pressure (ratio of VVV in CEE vs. placebo, 1.04, P<0.001; ratio of VVV in CEE+MPA vs. placebo, 1.05, P<0.001).
Conclusions
Among postmenopausal women, CEE and CEE+MPA at conventional doses increased mean and VVV of systolic blood pressure.
doi:10.1097/HJH.0000000000000287
PMCID: PMC4180281  PMID: 24991872
hypertension; blood pressure; postmenopause; women; hormone therapy
16.  Potassium intake and risk of stroke in hypertensive and non-hypertensive women in the Women’s Health Initiative 
Background and Purpose
Dietary potassium has been associated with lower risk of stroke but there is little data on dietary potassium effects on different stroke subtypes or in older hypertensive and non-hypertensive women.
Methods
The study population consisted of 90,137 postmenopausal women aged 50–79 at enrollment, free of stroke history at baseline, followed prospectively for an average of 11 years. Outcome variables were total, ischemic, and hemorrhagic stroke, and all-cause mortality. Incidence was compared across quartiles of dietary potassium intake and hazard ratios were obtained from Cox proportional hazards models after adjusting for potential confounding variables, and in hypertensive and non-hypertensive women separately.
Results
Mean dietary potassium intake was 2611 mg/day. Highest quartile of potassium intake was associated with lower incidence of ischemic and hemorrhagic stroke, and total mortality. Multivariate analyses comparing highest to lowest quartile of potassium intake, indicated a hazard ratio (HR) for all-cause mortality of 0.90 (95% CI: 0.85 – 0.95), for all stroke of HR=0.88 (95% CI: 0.79 – 0.98), and for ischemic stroke of 0.84 (95% CI: 0.74 – 0.96). The effect on ischemic stroke was more apparent in non-hypertensive women among whom there was a 27% lower risk with HR of 0.73 (95% CI: 0.60 – 0.88), interaction p-value <.10. There was no association with hemorrhagic stroke.
Conclusions
High potassium intake is associated with a lower risk of all stroke and ischemic stroke as well as all-cause mortality in older women, particularly those who are not hypertensive.
doi:10.1161/STROKEAHA.114.006046
PMCID: PMC4175295  PMID: 25190445
stroke; dietary potassium; hypertension; Women’s Health Initiative
17.  Improvement in Stroke Risk Prediction: Role of c-reactive protein (CRP) and Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) in the Women’s Health Initiative 
Background and Purpose
Classification of risk of ischemic stroke is important for medical care and public health reasons. Whether addition of biomarkers adds to predictive power of the Framingham Stroke Risk or other traditional risk factors has not been studied in older women.
Methods
The Hormones and Biomarkers Predicting Stroke (HaBPS) Study is a case-control study of blood biomarkers assayed in 972 ischemic stroke cases and 972 controls, nested in the Women’s Health Initiative Observational Study of 93,676 postmenopausal women followed for an average of 8 years. We evaluated additive predictive value of two commercially available biomarkers: c-reactive protein (CRP) and Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) to determine if they added to risk prediction by the Framingham Stroke Risk Score (FSRS) or by traditional risk factors (TRF) which included lipids and other variables not included in the FSRS. As measures of additive predictive value, we used the c-statistic, Net Reclassification Improvement (NRI), category-less NRI, and Integrated Discrimination Improvement Index (IDI).
Results
Addition of CRP to Framingham risk models or additional traditional risk factors overall modestly improved prediction of ischemic stroke and resulted in overall NRI of 6.3%, (case NRI=3.9%, control NRI=2.4%) .In particular, hs-CRP was useful in prediction of cardioembolic strokes (NRI=12.0%; 95%CI: 4.3-19.6%) and in strokes occurring in less than 3 years (NRI=7.9%, 95%CI: 0.8-14.9%). Lp-PLA2 was useful in risk prediction of large artery strokes (NRI=19.8%, 95%CI: 7.4 -32.1%) and in early strokes (NRI=5.8%, 95%CI: 0.4-11.2%).
Conclusions
CRP and Lp-PLA2 can improve prediction of certain subtypes of ischemic stroke in older women, over the Framingham stroke risk model and traditional risk factors, and may help to guide surveillance and treatment of women at risk.
doi:10.1111/j.1747-4949.2012.00860.x
PMCID: PMC3556354  PMID: 23088183
18.  Associations of chronic stress burden, perceived stress, and traumatic stress with cardiovascular disease prevalence and risk factors in the HCHS/SOL Sociocultural Ancillary Study 
Psychosomatic medicine  2014;76(6):468-475.
Objective
The current study examined multiple stress indicators (chronic, perceived, traumatic) in relation to prevalent coronary heart disease (CHD), stroke, and major cardiovascular disease (CVD) risk factors (i.e., diabetes, dyslipidemia, hypertension, current smoking) in the multi-site Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Sociocultural Ancillary Study (2010–2011).
Methods
Participants were 5313 men and women, 18–74 years old, representing diverse Hispanic/Latino ethnic backgrounds, who underwent a comprehensive baseline clinical exam and sociocultural exam with measures of stress.
Results
Chronic stress burden was related to a higher prevalence of CHD after adjusting for sociodemographic, behavioral and biological risk factors [OR (95% CI) = 1.22, (1.10–1.36)] and related to stroke prevalence in the model adjusted for demographic and behavioral factors [OR (95% CI) = 1.26, (1.03–1.55∂)]. Chronic stress was also related to a higher prevalence of diabetes [OR=1.20, (1.11–1.31)] and hypertension [OR=1.10 (1.02–1.19)] in individuals free from CVD (N=4926). Perceived stress [OR=1.03 (1.01–1.05)] and traumatic stress [OR=1.15 (1.05–1.26)] were associated with a higher prevalence of smoking. Participants who reported a greater number of lifetime traumatic events also unexpectedly showed a lower prevalence of diabetes [OR=.89 (.83–.97)] and hypertension [OR=.88 (.82–.93)]. Effects were largely consistent across age and sex groups.
Conclusions
The study underscores the utility of examining multiple indicators of stress in relation to health, since the direction and consistency of associations may vary across distinct stress conceptualizations. In addition, the study suggests that chronic stress is related to higher CVD risk and prevalence in Hispanics/Latinos, the largest U.S. ethnic minority group.
doi:10.1097/PSY.0000000000000069
PMCID: PMC4349387  PMID: 24979579
Cardiovascular Disease; Coronary Heart Disease; Hispanic; Latino; Stress
19.  High Cholesterol Awareness, Treatment, and Control Among Hispanic/Latinos: Results From the Hispanic Community Health Study/Study of Latinos 
Background
We assessed high cholesterol (HC) awareness, treatment, and control rates among US Hispanic/Latino adults and describe factors associated with HC awareness and management.
Methods and Results
Baseline data (collected 2008–2011) from a multisite probability sample of Hispanic/Latino adults in the Hispanic Community Health Study/Study of Latinos (18 to 74 years old; N=16 207) were analyzed. HC was defined as low-density lipoprotein-cholesterol ≥130 mg/dL and/or total cholesterol ≥240 mg/dL or use of cholesterol-lowering medication. Among Hispanic/Latino adults with HC, almost half (49.3%) were not aware of their condition and only 29.5% were receiving treatment. Men had a higher HC prevalence than women (44.0% versus 40.5%) but a lower rate of treatment (28.1% versus 30.6%). Younger adults were significantly less likely to be HC aware compared to those who were older. Those with hypertension, diabetes, and high socioeconomic position were more likely to be HC aware. US-born Hispanic/Latino were more likely to be HC unaware than foreign-born Hispanics/Latinos, but longer US residency was significantly associated with being HC aware, treated, and controlled. Cholesterol control was achieved among 64.3% of those who were HC treated. However, younger adults, women, those with lower income, those uninsured, and more recent immigrants were less likely to be HC controlled. Individuals of Puerto Rican or Dominican background were most likely to be HC aware and treated, whereas those of Mexican or Central American background were least likely to be HC treated. Individuals of Cuban and South American background had the lowest rates of HC control, whereas Puerto Ricans had the highest.
Conclusions
Understanding gaps in HC awareness, treatment, and control among US Hispanic/Latino adults can help inform physicians and policymakers to improve disease management and patient education programs.
doi:10.1161/JAHA.115.001867
PMCID: PMC4608071  PMID: 26109505
cholesterol; epidemiology; health disparities; high-risk populations
20.  Prevalence of Hypertension, Awareness, Treatment, and Control in the Hispanic Community Health Study/Study of Latinos 
American Journal of Hypertension  2014;27(6):793-800.
BACKGROUND
The prevention and control of hypertension is an essential component for reducing the burden of cardiovascular diseases. Here we describe the prevalence of hypertension in diverse Hispanic/Latino background groups and describe the proportion who are aware of their diagnosis, receiving treatment, and having their hypertension under control.
METHODS
The Hispanic Community Health Study/Study of Latinos is a longitudinal cohort study of 16,415 Hispanics/Latinos, aged 18–74 years from 4 US communities (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA). At baseline (2008–2011) the study collected extensive measurements and completed questionnaires related to research on cardiovascular diseases. Hypertension was defined as measured blood pressure ≥140/90mm Hg or use of antihypertensive medication.
RESULTS
The total age-adjusted prevalence of hypertension in this study was 25.5% as compared with 27.4% in non-Hispanic whites in the National Health and Nutrition Examination Survey. Prevalence of hypertension increased with increasing age groups and was highest in Cuban, Puerto Rican, and Dominican background groups. The percent with hypertension who were aware, being treated with medication, or had their hypertension controlled was lower compared with US non-Hispanic whites with hypertension and it was lowest in those without health insurance.
CONCLUSIONS
These findings indicate a significant deficit in treatment and control of hypertension among Hispanics/Latinos residing in the United States, particularly those without health insurance. Given the relative ease of identification of hypertension and the availability of low-cost medications, enabling better access to diagnostic and treatment services should reduce the burden of hypertension in Hispanic populations.
doi:10.1093/ajh/hpu003
PMCID: PMC4017932  PMID: 24627442
blood pressure; epidemiology; Hispanics; hypertension; Latinos; medically uninsured; socioeconomic status.
21.  Agreement between TOAST and CCS ischemic stroke classification 
Neurology  2014;83(18):1653-1660.
Objective:
The objective of this study was to assess the level of agreement between stroke subtype classifications made using the Trial of Org 10172 Acute Stroke Treatment (TOAST) and Causative Classification of Stroke (CCS) systems.
Methods:
Study subjects included 13,596 adult men and women accrued from 20 US and European genetic research centers participating in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN). All cases had independently classified TOAST and CCS stroke subtypes. Kappa statistics were calculated for the 5 major ischemic stroke subtypes common to both systems.
Results:
The overall agreement between TOAST and CCS was moderate (agreement rate, 70%; κ = 0.59, 95% confidence interval [CI] 0.58–0.60). Agreement varied widely across study sites, ranging from 28% to 90%. Agreement on specific subtypes was highest for large-artery atherosclerosis (κ = 0.71, 95% CI 0.69–0.73) and lowest for small-artery occlusion (κ = 0.56, 95% CI 0.54–0.58).
Conclusion:
Agreement between TOAST and CCS diagnoses was moderate. Caution is warranted when comparing or combining results based on the 2 systems. Replication of study results, for example, genome-wide association studies, should utilize phenotypes determined by the same classification system, ideally applied in the same manner.
doi:10.1212/WNL.0000000000000942
PMCID: PMC4223086  PMID: 25261504
22.  Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease 
Angelantonio, Emanuele Di | Gao, Pei | Khan, Hassan | Butterworth, Adam S. | Wormser, David | Kaptoge, Stephen | Kondapally Seshasai, Sreenivasa Rao | Thompson, Alex | Sarwar, Nadeem | Willeit, Peter | Ridker, Paul M | Barr, Elizabeth L.M. | Khaw, Kay-Tee | Psaty, Bruce M. | Brenner, Hermann | Balkau, Beverley | Dekker, Jacqueline M. | Lawlor, Debbie A. | Daimon, Makoto | Willeit, Johann | Njølstad, Inger | Nissinen, Aulikki | Brunner, Eric J. | Kuller, Lewis H. | Price, Jackie F. | Sundström, Johan | Knuiman, Matthew W. | Feskens, Edith J. M. | Verschuren, W. M. M. | Wald, Nicholas | Bakker, Stephan J. L. | Whincup, Peter H. | Ford, Ian | Goldbourt, Uri | Gómez-de-la-Cámara, Agustín | Gallacher, John | Simons, Leon A. | Rosengren, Annika | Sutherland, Susan E. | Björkelund, Cecilia | Blazer, Dan G. | Wassertheil-Smoller, Sylvia | Onat, Altan | Marín Ibañez, Alejandro | Casiglia, Edoardo | Jukema, J. Wouter | Simpson, Lara M. | Giampaoli, Simona | Nordestgaard, Børge G. | Selmer, Randi | Wennberg, Patrik | Kauhanen, Jussi | Salonen, Jukka T. | Dankner, Rachel | Barrett-Connor, Elizabeth | Kavousi, Maryam | Gudnason, Vilmundur | Evans, Denis | Wallace, Robert B. | Cushman, Mary | D’Agostino, Ralph B. | Umans, Jason G. | Kiyohara, Yutaka | Nakagawa, Hidaeki | Sato, Shinichi | Gillum, Richard F. | Folsom, Aaron R. | van der Schouw, Yvonne T. | Moons, Karel G. | Griffin, Simon J. | Sattar, Naveed | Wareham, Nicholas J. | Selvin, Elizabeth | Thompson, Simon G. | Danesh, John
JAMA  2014;311(12):1225-1233.
IMPORTANCE
The value of measuring levels of glycated hemoglobin (HbA1c) for the prediction of first cardiovascular events is uncertain.
OBJECTIVE
To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk.
DESIGN, SETTING, AND PARTICIPANTS
Analysis of individual-participant data available from 73 prospective studies involving 294 998 participants without a known history of diabetes mellitus or CVD at the baseline assessment.
MAIN OUTCOMES AND MEASURES
Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5%to <7.5%), and high (≥7.5%) risk.
RESULTS
During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20 840 incident fatal and nonfatal CVD outcomes (13 237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA1c values and CVD risk. The association between HbA1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA1c was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (−0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels.
CONCLUSIONS AND RELEVANCE
In a study of individuals without known CVD or diabetes, additional assessment of HbA1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk.
doi:10.1001/jama.2014.1873
PMCID: PMC4386007  PMID: 24668104
23.  The Adipokine Profile of Metabolically Benign Obese and At-Risk Normal Weight Postmenopausal Women: The Women’s Health Initiative Observational Study 
Obesity (Silver Spring, Md.)  2013;22(3):786-794.
Nearly a third of obese individuals, termed metabolically benign obese, have a low burden of adiposity-related cardiometabolic abnormalities, while a substantial proportion of normal weight individuals possess risk factors. In cross-sectional analyses of 699 normal weight and 1294 overweight/obese postmenopausal women enrolled in a nested case-control stroke study ancillary to the Women’s Health Initiative Observational Study, we compared levels of adiponectin, leptin, and resistin among metabolically benign normal weight, at-risk normal weight, metabolically benign obese, and at-risk obese women using components of the ATP III definition of the metabolic syndrome (metabolically benign: ≤1 of the 4 components; at-risk phenotype: ≥2 components or diabetes). Overall, 382/699 normal weight women (54.6%) and 328/1194 overweight/obese women (27.5%) were metabolically benign. Among normal weight women, at-risk women had higher leptin and lower adiponectin levels compared to metabolically benign women; multivariate-adjusted odds ratios were significant for having leptin (OR: 2.51; 95% CI: 1.28–5.01) and resistin (1.46; 1.03–2.07) in the top tertile and adiponectin in the bottom tertile (2.64; 1.81–3.84). Compared to metabolically benign overweight/obese women, at-risk obese women had higher odds of having leptin in the top tertile (1.62; 1.24–2.12) and adiponectin in the bottom tertile (2.78; 2.04–3.77). Overall, metabolically benign overweight/obese women had an intermediate adipokine profile (between at-risk obese and metabolically benign normal weight women), while at-risk normal weight women had a less favorable profile compared to metabolically benign normal weight women. As adiponectin was the only adipokine independent of BMI, it may be most likely to have a role in the etiological pathway of these phenotypes.
doi:10.1002/oby.20139
PMCID: PMC3883802  PMID: 24357553
postmenopausal women; adipose tissue; obesity; adipokines
24.  Prevalence and Incident Prehypertension and Hypertension in Postmenopausal Hispanic Women: Results from the Women’s Health Initiative 
American Journal of Hypertension  2014;27(3):372-381.
BACKGROUND
There is a paucity of research on prehypertension and incident hypertension among postmenopausal Hispanic women. The overall objective is to determine the multiple risk factors associated with the prevalence of hypertension status at baseline and incident hypertension at year 3 in postmenopausal Hispanic women.
METHODS
For the analyses in this paper, we included a total of 4,680 Hispanic women who participated in the Women’s Health Initiative (WHI), a randomized clinical trial and observational study, at baseline (1994–1998) and at third-year follow-up and for whom blood pressure was measured at year 3 (n = 3,848). Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of hypertension status, defined as systolic blood pressure ≥140mm Hg and/or diastolic blood pressure ≥90mm Hg, to assess the odds of incident hypertension at year 3 of follow-up in association with the factors included in the baseline models.
RESULTS
At year 3 of follow-up, 27.3% of Hispanic women who were normotensive at baseline had progressed to prehypertension, and 9.0% had become hypertensive. Among the prehypertensive participants at baseline, 30.4% had progressed to hypertension. Compared with normotensive Hispanic women, hypertensive participants had a higher number of cardiovascular risk factors: body mass index ≥30kg/m2 (OR = 3.76; 95% CI = 3.01–4.71), a family history of diabetes, stroke, and/or myocardial infarction (OR = 1.12; 95% CI 1.03–1.23), treated hypercholesterolemia (OR = 1.57; 95% CI = 1.23–1.99), treated diabetes (OR = 2.04; 95% CI = 1.40–2.97), and a history of cardiovascular disease (OR = 2.04; 95% CI = 1.58–2.64).
CONCLUSIONS
Hispanic women seem to experience an increased risk of incident hypertension in later adulthood. On a practical level, recommendations for preventive care and population-wide adoption of health behaviors, such as community-focused campaigns to engage in physical activity, may contribute to reductions in hypertension risk factors.
CLINICAL TRIALS REGISTRATION
Trial Number NCT00000611
doi:10.1093/ajh/hpt279
PMCID: PMC3915745  PMID: 24480867
blood pressure; cardiovascular risk; Hispanic; hypertension; postmenopausal; women; Women’s Health Initiative
25.  Statin use and risk of haemorrhagic stroke in a community-based cohort of postmenopausal women: an observational study from the Women's Health Initiative 
BMJ Open  2015;5(2):e007075.
Objectives
To determine whether statin treatment is associated with increased risk of haemorrhagic stroke (HS) in older women. A secondary objective was to evaluate HS risk in users of combined statin and antiplatelet treatment.
Design
Observational study: secondary data analysis from the Women's Health Initiative (WHI) clinical trials.
Setting
Women were recruited from 40 participating sites.
Participants
Cohort of 68 132 women followed through 2005 (parent study) and for an additional 5 years in the extension study.
Main outcome measures
Statin use was assessed at baseline and at follow-up visits (1, 3, 6 and 9 years). Women brought medications in original containers for inventory. Strokes were ascertained semiannually and centrally adjudicated. Risk of HS by statin use (time-varying covariate, with the ‘no use’ category as the referent) was estimated from Cox proportional hazard regression models adjusted for age (model 1); risk factors for HS (model 2); and possible confounders by indication (model 3). Prespecified subgroup analyses were conducted by use of antiplatelet medications.
Results
Final models included 67 882 women (mean age, 63±7 years). Over a mean follow-up of 12 years, incidence rates of HS were 6.4/10 000 person-years among statin users and 5.0/10 000 person-years among non-users (p=0.11). The unadjusted risk of HS in statin users was 1.21 (CI 0.96 to 1.53); after adjusting for age and HS risk factors the HR was 0.98 (CI 0.76 to 1.26). Risk of HS was higher among women on statins and antiplatelet agents versus women on antiplatelet medications alone (HR=1.59; CI 1.03 to 2.47); p for interaction=0.011.
Conclusions
This retrospective analysis did not show an association between statin use and HS risk among older women. HS risk was higher among women taking statins with antiplatelet agents. These findings warrant further investigation, given potential implications for clinical decision-making.
doi:10.1136/bmjopen-2014-007075
PMCID: PMC4342587  PMID: 25716175
PREVENTIVE MEDICINE

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