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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.  The Role of Epidemiology in the Era of Molecular Epidemiology and Genomics: Summary of the 2013 AJE-sponsored Society of Epidemiologic Research Symposium 
American Journal of Epidemiology  2013;178(9):1350-1354.
On June 20, 2013, the American Journal of Epidemiology sponsored a symposium at the Society for Epidemiologic Research's 46th Annual Meeting in Boston, Massachusetts, entitled, “What Is the Role of Epidemiology in the Era of Molecular Biology and Genomics?” The future of epidemiology depends on innovation in generating interesting and important testable hypotheses that are relevant to population health. These new strategies will depend on new technology, both in measurement of agents and environment and in the fields of pathophysiology and outcomes, such as cellular epidemiology and molecular pathology. The populations to be studied, sample sizes, and study designs should be selected based on the hypotheses to be tested and include case-control, cohort, and clinical trials. Developing large mega cohorts without attention to specific hypotheses is inefficient, will fail to address many associations with high-quality data, and may well produce spurious results.
doi:10.1093/aje/kwt239
PMCID: PMC3988450  PMID: 24105654
immunology; pathology; study design
3.  Rheumatoid Arthritis in the Women's Health Initiative: Methods and Baseline Evaluation 
American Journal of Epidemiology  2014;179(7):917-926.
Second-generation assays for anti-cyclic citrullinated peptide (anti-CCP), a highly sensitive and specific marker for rheumatoid arthritis (RA), have redefined the epidemiology of RA. In the Women's Health Initiative (WHI) RA study (2009–2011), we evaluated the prevalence of anti-CCP positivity among 15,691 (10.2% of 161,808) WHI participants aged 50–79 years who reported RA. Using stored baseline specimens, we measured serum anti-CCP, rheumatoid factor (RF), and antinuclear antibody in a defined sample of 9,988 of black, white, and Hispanic women. In a subset of women, we measured plasma cytokine levels and number of copies of the human leukocyte antigen (HLA)-DRB1 (HLA-DRB1) shared epitope in DNA by means of Luminex polymerase chain reaction typing (Luminex Corporation, Austin, Texas). We validated classification of probable clinical RA in 2 clinics as anti-CCP positivity or self-reported validated use of disease-modifying antirheumatic drugs (DMARDs). The prevalence of anti-CCP positivity was 8.1%, and the prevalence of RF positivity was approximately 16.0%. DMARD use including prednisone was reported by 1,140 (11.4%) participants (841 excluding prednisone) but by 57.5% of anti-CCP-positive women. The prevalence of 2 shared epitopes was also much higher for anti-CCP-positive women (18.2%, as opposed to only 5.5% for women with anti-CCP-negative DMARD-positive RA and 6.6% for anti-CCP-negative, RF-negative DMARD nonusers). Median cytokine levels were much higher for anti-CCP-positive/RF-positive women. Women with anti-CCP-positive RA and anti-CCP-negative RA had different characteristics with regard to HLA shared epitope, cigarette smoking, and inflammation (cytokines).
doi:10.1093/aje/kwu003
PMCID: PMC3969537  PMID: 24569640
cytokines; epidemiologic methods; genetics; rheumatoid arthritis
4.  HIV Infection, Antiretroviral Therapy Initiation and Longitudinal Changes in Biomarkers of Organ Function§ 
Current HIV research  2014;12(1):50-59.
Background
HIV is associated with end-organ diseases of aging via unclear mechanisms. Longitudinally assessing how HIV infection and ART initiation affect biomarkers of end organ function/disease could clarify these mechanisms. We investigated longitudinal changes in clinical biomarkers following 1) HIV infection and 2) ART initiation with evidence of viral suppression.
Methods
Cohort: Veterans Aging Cohort Study Virtual Cohort (VACS VC). VACS VC is a longitudinal cohort of HIV infected (HIV+) and race-ethnicity, sex, age, and clinical site-matched uninfected Veterans enrolled in the same calendar year. Inclusion criteria: a negative and successively positive (>six months) HIV antibody test. We used Wilcoxon signed-rank tests to analyze 1) the effect of HIV infection on lipids, renal, hepatic and hematologic/cardiovascular biomarkers and 2)whether ART initiation with HIV-1 RNA<500 cpm reverts any changes back to pre-HIV levels
Results
422 Veterans had at least 1 biomarker measurement available prior to HIV infection and prior to ART initiation. 297 had at least 1 biomarker measurement available prior to HIV infection and after ART initiation with evidence of viral suppression. Mean age prior to HIV infection was 43 years. HIV infection was associated with reduction in total cholesterol, HDL cholesterol, LDL cholesterol, serum albumin, ALT, platelet count, hemoglobin and elevation of FIB-4 score and triglycerides. These changes occurred without significant changes in BMI. ART initiation (with HIV-1 RNA<500cpm) did not reverse alteration in triglycerides, LDL cholesterol, hemoglobin, or FIB-4 to pre-HIV infection levels.
Conclusions
HIV infection is associated with longitudinal changes in serum levels of several biomarkers of end-organ function/disease and mortality. Multiple biomarkers (triglycerides, LDL cholesterol, hemoglobin, and FIB-4) remain altered from levels prior to HIV infection levels even following inititiation of ART and evidence of viral suppression. These results give insights into underlying mechanisms of increased risk for aging-related chronic diseases in the context of HIV infection.
PMCID: PMC4495647  PMID: 25034208
Clinical biomarkers; chronic diseases of aging; HIV infection; lipids
5.  Association of inflammatory markers with subclinical atherosclerosis in middle-aged white, Japanese-American, and Japanese men: the ERA-JUMP Study 
Aim
To examine whether the inflammatory markers, C-reactive protein (CRP) and fibrinogen, are associated with biomarkers of atherosclerosis [carotid intima-media thickness (IMT) and coronary artery calcification (CAC)] in the general male population, including Asians.
METHODS
Population-based samples of 310 Japanese, 293 Japanese-American and 297 White men aged 40-49 years without clinical cardiovascular disease had IMT, CAC, CRP and fibrinogen levels, and other conventional risk factors measured using standardized methods. Statistical associations between the variables were evaluated using multiple linear or logistic regression models.
RESULTS
The Japanese group had significantly lower levels of inflammatory markers and subclinical atherosclerosis than the Japanese-American and White groups (P-values all <0.001). The mean levels of CRP were 0.66 vs. 1.11 and 1.47 mg/L, and fibrinogen 255.0 vs. 313.0 and 291.5 mg/dl, respectively. Mean carotid IMT was 0.61 vs. 0.73 and 0.68 mm, and the prevalence of CAC 11.6% vs. 32.1% and 26.3%, respectively. Body mass index (BMI) showed significant positive associations with both CRP and fibrinogen levels. Although CRP showed a significant positive association with IMT in Japanese men, this association became non-significant after adjustment for traditional risk factors or BMI. In all three populations, CRP was not associated significantly with the prevalence of CAC. Similarly, fibrinogen did not show a significant association with either IMT or the prevalence of CAC.
CONCLUSIONS
The associations of inflammatory markers with subclinical atherosclerosis may merely reflect the strong association of BMI with inflammatory markers and subclinical atherosclerosis in both Eastern and Western populations.
doi:10.5551/jat.23580
PMCID: PMC4449327  PMID: 25445888
obesity; C-reactive protein; fibrinogen; intima-media thickness; coronary artery calcification
6.  The Women on the Move Through Activity and Nutrition (WOMAN) Study: Final 48-Month Results 
Obesity (Silver Spring, Md.)  2011;20(3):636-643.
The Women on the Move through Activity and Nutrition (WOMAN) study was designed to test whether a nonpharmacological intervention including qualitative and quantitative dietary changes to induce weight loss and increased physical activity levels would reduce blood triglyceride levels and number of low-density lipoprotein particles (LDL-P). Such decreases in lipoproteins and other risk factors could reduce or slow progression of subclinical cardiovascular disease (CVD). Study participants were randomized to either the intervention (Lifestyle Change) or assessment (Health Education) group. Most of the intervention ended at the 30-month visit. The last 48-month examination was completed in 9/2008. There was very substantial weight loss and increased exercise during the first 30 months of the trial resulting in significant decreases in CV risk factors. Most of the intervention effect was lost through 48 months. Weight loss was 3.4 kg in Lifestyle Intervention and 0.2 kg in the Health Education at 48 months (P = 0.000). There were no significant changes at 48 months in lipid levels, blood pressure (BP), glucose, insulin, or in the subclinical measures of coronary calcium, carotid intima media thickness, or plaque. There was a significant decrease in long-distance corridor walk time in the Lifestyle vs. Health Education groups. Significant lifestyle changes can be achieved that result in decreases in CV risk factors. Whether such changes reduce CV outcomes is still untested in clinical trials of weight loss or exercise. Long-term maintenance of successful lifestyle changes, weight loss and reduced risk factors is the hurdle for lifestyle interventions attempting to prevent CV and other chronic diseases.
doi:10.1038/oby.2011.80
PMCID: PMC3623568  PMID: 21494228
7.  HYPERTENSION AND OBESITY AND THE RISK OF KIDNEY CANCER IN TWO LARGE COHORTS OF US MEN AND WOMEN 
Hypertension  2014;63(5):934-941.
Kidney cancer incidence is increasing globally. Reasons for this rise are unclear, but could relate to obesity and hypertension. We analyzed longitudinal relationships between hypertension and obesity and kidney cancer incidence in 156,774 participants of the Women’s Health Initiative (WHI) clinical trials and observational studies over 10.8 years. In addition, we examined the impact of blood pressure (BP) on kidney cancer deaths over 25 years among the 353,340 men screened for the Multiple Risk Factor Intervention Trial (MRFIT). In the WHI, systolic SBP was categorized in 6 groups from <120 to >160 mmHg and body mass index (BMI) was categorized using standard criteria. In age-adjusted analyses, kidney cancer risk increased across SBP categories (p-value for trend <0.0001) and BMI categories (p-value for trend <0.0001). In adjusted Cox proportional hazards models, both SBP levels and BMI were predictors of kidney cancer. In the MRFIT sample, there were 906 deaths after an average of 25 years of follow-up attributed to kidney cancer amongst the 353,340 participants aged 35–57 years at screening. The risk of death from kidney cancer increased in a dose-response fashion with increasing SBP (HR=1.87 for SBP>160 versus <120 mmHg; 95% CI, 1.38–2.53). Risk was increased among cigarette smokers. Further research is needed to determine the pathophysiologic basis of relationships between both higher BP and the risk of kidney cancer, and whether specific drug therapies for hypertension can reduce kidney cancer risk.
doi:10.1161/HYPERTENSIONAHA.113.02953
PMCID: PMC4098147  PMID: 24637660
blood pressure; body weight; epidemiology; kidney neoplasms; obesity; women’s health
8.  Use of Interrupted Time-Series Method to Evaluate the Impact of Cigarette Excise Tax Increases in Pennsylvania, 2000–2009 
Introduction
Scientific evidence shows that cigarette price increases can significantly reduce smoking prevalence and smoking initiation among adolescents and young adults. However, data are lacking regarding the effectiveness of increasing Pennsylvania’s cigarette tax to reduce smoking and/or adverse health effects of smoking. The objective of our study was to assess the impact of cigarette tax increases and resulting price increases on smoking prevalence, acute myocardial infarction (AMI) and asthma hospitalization rates, and sudden cardiac death (SCD) rates in Pennsylvania.
Methods
We used segmented regression analyses of interrupted time series to evaluate the level and trend changes in Pennsylvania adults’ current smoking prevalence, age-adjusted AMI and asthma hospitalization rates, age-specific asthma hospitalization rates, and age-adjusted SCD rates following 2 cigarette excise tax increases.
Results
After the first excise tax increase, no beneficial effects were noted on the outcomes of interest. The second tax increase was associated with significant declines in smoking prevalence for people aged 18 to 39, age-adjusted AMI hospitalization rates for men, age-adjusted asthma hospitalizations rates, and SCD rates among men. Overall smoking prevalence declined by 5.2% (P = .01), with a quarterly decrease of 1.4% (P = .01) for people aged 18 to 39 years. The age-adjusted AMI hospitalization rate for men showed a decline of 3.87/100,000 population (P = .04). The rate of age-adjusted asthma hospitalizations decreased by 10.05/100,000 population (P < .001), and the quarterly trend decreased by 3.21/100,000 population (P < .001). Quarterly SCD rates for men decreased by 1.34/100,000 population (P < .001).
Conclusion
An increase in the price of cigarettes to more than $4 per 20-cigarette pack was associated with a significant decrease in smoking among younger people (aged 18–39). Decreases were also seen in asthma hospitalizations and men’s age-adjusted AMI hospitalization and SCD rates. Further research and policy development regarding the effect of cigarette taxes on tobacco consumption should be cognizant of the psychological tipping points at which overall price affects smoking patterns.
doi:10.5888/pcd10.120268
PMCID: PMC3804017  PMID: 24135393
9.  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
10.  Brain Cholesterol Metabolism, Oxysterols, and Dementia 
Cholesterol metabolism is implicated in the etiology of Alzheimer’s disease (AD) and amyloid production in the brain. While brain cholesterol cannot be measured directly in vivo, the oxysterol, 24S-hydroxycholesterol (24-OHC), is the predominant metabolite of brain cholesterol and can be measured in the blood. The aim of this review is to evaluate plasma 24-OHC as a potential biomarker of AD risk and discuss factors related to its levels in the brain and blood. This systematic review examines studies published between 1950 and June 2012 that examined the relationship between plasma 24-OHC, cognition, brain structure, and dementia using the following key words (“24S-hydroxycholesterol” or “24-hydroxycholesterol”) and (“Brain” or “Cognitive”). We found a total of 28 studies of plasma 24-OHC and neurodegenerative disease, including a subset of 12 that used dementia as a clinical endpoint. These studies vary in the direction of the observed associations. Results suggest plasma 24-OHC may be higher in the early stages of cognitive impairment and lower in more advanced stages of AD when compared to cognitively normal controls. Measures of 24-OHC in the blood may be an important potential marker for cholesterol metabolism in the brain and risk of AD. Further studies of plasma 24-OHC and dementia must account for the stage of disease, establish the temporal trends in oxysterol concentrations, and employ neuroimaging modalities to assess the structural and metabolic changes occurring in the brain prior to the onset of cognitive impairment.
doi:10.3233/JAD-2012-121585
PMCID: PMC4354887  PMID: 23076077
Alzheimer’s disease; brain; dementia; 24-hydroxycholesterol; 24S-hydroxycholesterol; oxysterols
11.  Myocardial extracellular volume fraction quantified by cardiovascular magnetic resonance is increased in diabetes and associated with mortality and incident heart failure admission 
European Heart Journal  2013;35(10):657-664.
Aims
Diabetes may promote myocardial extracellular matrix (ECM) expansion that increases vulnerability. We hypothesized that: (i) type 2 diabetes would be associated with quantitative cardiovascular magnetic resonance (CMR) measures of myocardial ECM expansion, i.e. extracellular volume fraction (ECV); (ii) medications blocking the renin–angiotensin–aldosterone system (RAAS) would be associated with lower ECV; and (iii) ECV in diabetic individuals would be associated with mortality and/or incident hospitalization for heart failure.
Methods and results
We enrolled 1176 consecutive patients referred for CMR without amyloidosis and computed ECV from measures of the haematocrit and myocardial and blood T1 pre- and post-contrast. Linear regression modelled ECV; Cox regression modelled mortality and/or hospitalization for heart failure. Diabetic individuals (n = 231) had higher median ECV than those without diabetes (n = 945): 30.2% (IQR: 26.9–32.7) vs. 28.1% (IQR: 25.9–31.0), respectively, P < 0.001). Diabetes remained associated with higher ECV in models adjusting for demographics, comorbidities, and medications (P < 0.001). Renin–angiotensin–aldosterone system blockade was associated with lower ECV (P = 0.028) in multivariable linear models. Over a median of 1.3 years (IQR: 0.8–1.9), 38 diabetic individuals had events (21 incident hospitalizations for heart failure; 24 deaths), and ECV was associated with these events (HR: 1.52, 95% CI: 1.21–1.89 per 3% ECV increase) in multivariable Cox regression models.
Conclusion
Diabetes is associated with increased ECV. Extracellular volume fraction detects amelioration of ECM expansion associated with RAAS blockade, and is associated with mortality and/or incident hospitalization for heart failure in diabetic individuals. Extracellular matrix expansion may be an important intermediate phenotype in diabetic individuals that is detectable and treatable.
doi:10.1093/eurheartj/eht193
PMCID: PMC3945798  PMID: 23756336
MRI; extracellular matrix; fibrosis; collagen; diabetes; extracellular volume fraction
12.  Developing a national strategy to prevent dementia: Leon Thal Symposium 2009 
Among the major impediments to the design of clinical trials for the prevention of Alzheimer's disease (AD), the most critical is the lack of validated biomarkers, assessment tools, and algorithms that would facilitate identification of asymptomatic individuals with elevated risk who might be recruited as study volunteers. Thus, the Leon Thal Symposium 2009 (LTS'09), on October 27–28, 2009 in Las Vegas, Nevada, was convened to explore strategies to surmount the barriers in designing a multisite, comparative study to evaluate and validate various approaches for detecting and selecting asymptomatic people at risk for cognitive disorders/dementia. The deliberations of LTS'09 included presentations and reviews of different approaches (algorithms, biomarkers, or measures) for identifying asymptomatic individuals at elevated risk for AD who would be candidates for longitudinal or prevention studies. The key nested recommendations of LTS'09 included: (1) establishment of a National Database for Longitudinal Studies as a shared research core resource; (2) launch of a large collaborative study that will compare multiple screening approaches and biomarkers to determine the best method for identifying asymptomatic people at risk for AD; (3) initiation of a Global Database that extends the concept of the National Database for Longitudinal Studies for longitudinal studies beyond the United States; and (4) development of an educational campaign that will address public misconceptions about AD and promote healthy brain aging.
doi:10.1016/j.jalz.2010.01.008
PMCID: PMC4298995  PMID: 20298968
Alzheimer's disease; Dementia; Mild cognitive impairment; Prevention; Biomarkers; Diagnosis; Screening; Clinical trials; MCI; Asymptomatic; Risk factors; Registry; Longitudinal studies; Database; PAD2020; Leon Thal Symposium; Treatment; Drug development; Health policy
13.  CD8+ T-Cells Count in Acute Myocardial Infarction in HIV Disease in a Predominantly Male Cohort 
BioMed Research International  2015;2015:246870.
Human Immunodeficiency Virus- (HIV-) infected persons have a higher risk for acute myocardial infarction (AMI) than HIV-uninfected persons. Earlier studies suggest that HIV viral load, CD4+ T-cell count, and antiretroviral therapy are associated with cardiovascular disease (CVD) risk. Whether CD8+ T-cell count is associated with CVD risk is not clear. We investigated the association between CD8+ T-cell count and incident AMI in a cohort of 73,398 people (of which 97.3% were men) enrolled in the U.S. Veterans Aging Cohort Study-Virtual Cohort (VACS-VC). Compared to uninfected people, HIV-infected people with high baseline CD8+ T-cell counts (>1065 cells/mm3) had increased AMI risk (adjusted HR = 1.82, P < 0.001, 95% CI: 1.46 to 2.28). There was evidence that the effect of CD8+ T-cell tertiles on AMI risk differed by CD4+ T-cell level: compared to uninfected people, HIV-infected people with CD4+ T-cell counts ≥200 cells/mm3 had increased AMI risk with high CD8+ T-cell count, while those with CD4+ T-cell counts <200 cells/mm3 had increased AMI risk with low CD8+ T-cell count. CD8+ T-cell counts may add additional AMI risk stratification information beyond that provided by CD4+ T-cell counts alone.
doi:10.1155/2015/246870
PMCID: PMC4320893  PMID: 25688354
14.  Risk of Suicide after Long Term Follow-up from Bariatric Surgery 
The American journal of medicine  2010;123(11):1036-1042.
Purpose
Bariatric surgery is recognized as the treatment of choice for class III obesity (body mass index >= 40) and has been increasingly recommended for obese patients. Prior research has suggested an excess of deaths due to suicide following bariatric surgery but few large long term follow up studies exist. We examined post-bariatric surgery suicides by time since operation, sex, age, and suicide death rates as compared to US suicide rates.
Methods
Medical data following bariatric operations performed on Pennsylvania residents between 01/01/1995 and 12/31/2004 were obtained from the Pennsylvania Health Care Cost and Containment Council. Matching mortality data from suicides between 09/1/1996 and 12/28/2006 were obtained from the Division of Vital Records, Pennsylvania State Department of Health.
Results
There were 31 suicides (16,683 operations), for an overall rate of 6.6/10,000, 13.7 per 10,000 among men and 5.2 per 10,000 among women. About 30% of suicides occurred within the first two years following surgery, with almost 70% occurring within three years. For every age category except the youngest, suicide rates were higher among men vs. women. Age and sex-matched suicide rates in the US population (ages 35–64) were 2.4/10,000 (men) and 0.7/10,000 (women).
Conclusions
Compared to age and sex-matched suicide rates in the U.S., there was a substantial excess of suicides among all patients who had bariatric surgery in Pennsylvania during a ten-year period. These data document a need to develop more comprehensive longer-term surveillance and follow-up methods in order to evaluate factors associated with post-bariatric surgery suicide.
doi:10.1016/j.amjmed.2010.06.016
PMCID: PMC4296730  PMID: 20843498
bariatric surgery; suicides; public health
15.  Prehypertension, Hypertension, and the Risk of Acute Myocardial Infarction in HIV-Infected and -Uninfected Veterans 
We found increased acute myocardial infarction risk among hypertensive and prehypertensive HIV-infected veterans compared to normotensive uninfected veterans, independent of confounding comorbidities.
Background. Compared to uninfected people, human immunodeficiency virus (HIV)–infected individuals may have an increased risk of acute myocardial infarction (AMI). Currently, HIV-infected people are treated to the same blood pressure (BP) goals (<140/90 or <130/80 mm Hg) as their uninfected counterparts. Whether HIV-infected people with elevated BP have excess AMI risk compared to uninfected people is not known. This study examines whether the association between elevated BP and AMI risk differs by HIV status.
Methods. The Veterans Aging Cohort Study Virtual Cohort (VACS VC) consists of HIV-infected and -uninfected veterans matched 1:2 on age, sex, race/ethnicity, and clinical site. For this analysis, we analyzed 81 026 people with available BP data from VACS VC, who were free of cardiovascular disease at baseline. BP was the average of the 3 routine outpatient clinical measurements performed closest to baseline (first clinical visit after April 2003). BP categories used in the analyses were based on criteria of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Analyses were performed using Cox proportional hazards regression.
Results. Over 5.9 years (median), 860 incident AMIs occurred. Low/high prehypertensive and untreated/treated hypertensive HIV-infected individuals had increased AMI risk compared to uninfected, untreated normotensive individuals (hazard ratio [HR], 1.60 [95% confidence interval {CI}, 1.07–2.39]; HR, 1.81 [95% CI, 1.22–2.68]; HR, 2.57 [95% CI, 1.76–3.76]; and HR, 2.76 [95% CI, 1.90–4.02], respectively).
Conclusions. HIV, prehypertensive BP, and hypertensive BP were associated with an increased risk of AMI in a cohort of HIV-infected and -uninfected veterans. Future studies should prospectively investigate whether HIV interacts with BP to further increase AMI risk.
doi:10.1093/cid/cit652
PMCID: PMC3864500  PMID: 24065316
blood pressure; prehypertension; HIV; myocardial infarction
16.  Arterial Stiffness and β-Amyloid Progression in Nondemented Elderly Adults 
JAMA neurology  2014;71(5):562-568.
IMPORTANCE
Recent studies show that cerebral β-amyloid (Aβ) deposition is associated with blood pressure and measures of arterial stiffness in nondemented individuals.
OBJECTIVE
To examine the association between measures of arterial stiffness and change in Aβ deposition over time.
DESIGN, SETTING, AND PARTICIPANTS
Deposition of Aβ was determined in a longitudinal observational study of aging by positron emission tomography using the Pittsburgh compound B twice 2 years apart in 81 nondemented individuals 83 years and older. Arterial stiffness was measured with a noninvasive and automated waveform analyzer at the time closest to the second positron emission tomography scan. All measures were performed under standardized conditions. Pulse wave velocity (PWV) was measured in the central (carotid-femoral and heart-femoral PWV), peripheral (femoral-ankle PWV), and mixed (brachial-ankle PWV) vascular beds.
MAIN OUTCOMES AND MEASURES
The change in Aβ deposition over 2 years was calculated from the 81 individuals with repeat Aβ-positron emission tomography.
RESULTS
The proportion of Aβ-positive individuals increased from 48% at baseline to 75% at follow-up. Brachial-ankle PWV was significantly higher among Aβ-positive participants at baseline and follow-up. Femoral-ankle PWV was only higher among Aβ-positive participants at follow-up. Measures of central stiffness and blood pressure were not associated with Aβ status at baseline or follow-up, but central stiffness was associated with a change in Aβ deposition over time. Each standard deviation increase in central stiffness (carotid-femoral PWV, P = .001; heart-femoral PWV, P = .004) was linked with increases in Aβ deposition over 2 years.
CONCLUSIONS AND RELEVANCE
This study showed that Aβ deposition increases with age in nondemented individuals and that arterial stiffness is strongly associated with the progressive deposition of Aβ in the brain, especially in this age group. The association between Aβ deposition changes over time and generalized arterial stiffness indicated a relationship between the severity of subclinical vascular disease and progressive cerebral Aβ deposition.
doi:10.1001/jamaneurol.2014.186
PMCID: PMC4267249  PMID: 24687165
17.  Longitudinal Effects of Weight Loss and Regain on Cytokine Concentration in Obese Adults 
Objective
To describe patterns of weight loss and regain and their effect on the pro-inflammatory cytokines IL-6 and TNF-α, and anti-inflammatory cytokines adiponectin and IL-10 during a 24-month weight loss trial.
Materials/Methods
Participants were obese adults (N = 66) who lost and regained ≥10 lbs during a 24-month clinical trial of behavioral weight loss treatment. Measurements of cytokines and weight were conducted at baseline, 6, 12, 18, and 24 months. Linear mixed modeling was used to determine percent change in weight and cytokines from baseline.
Results
The sample was predominantly female (80.3%) and White (86.4%), with a mean age of 48.4 ± 7.3 years and mean BMI of 34.5 ± 4.4 kg/m2. At baseline, men had higher waist circumference, body weight, and energy intake, and lower percent body fat and adiponectin. The largest decrease in weight was observed at 6 months with a mean 11% decrease (p < .0001). A significant gender-by-weight change interaction on percent change in adiponectin was observed [b(se) = 0.9 (0.2), p = .0003], with men having a larger increase in adiponectin with weight loss compared to women. There was a significant effect of weight gain over time with increases in IL-6 [b(se) = 0.9 (0.3), p = .001].
Conclusions
Overall, weight loss was significantly associated with improvements in adiponectin and IL-6. Those improvements remained at 24 months, following weight regain. The association between weight change and adiponectin was different between genders. Implementing strategies that support sustained weight loss can help prevent a state of chronic systemic inflammation and its associated adverse effects.
doi:10.1016/j.metabol.2013.04.004
PMCID: PMC4266426  PMID: 23725640
Cytokines; behavioral weight loss; weight regain
18.  Temporal relationships between physical activity and sleep in older women 
Medicine and science in sports and exercise  2013;45(12):10.1249/MSS.0b013e31829e4cea.
Purpose
To examine the temporal and bidirectional relationship between accelerometer-derived physical activity estimates and actigraphy-assessed sleep characteristics among older women.
Methods
A sub-group of participants [N=143, mean age= 73y] enrolled in the Healthy Women Study wore an ActiGraph accelerometer on their waist and an Actiwatch sleep monitor on their wrist concurrently for 7-consecutive days. Multi-level models examined whether ActiGraph-assessed daily activity counts (ct·min·d-1) and moderate- to vigorous- intensity physical activity (MVPA; min·d-1) predicted Actiwatch-assessed sleep onset latency, total sleep time, sleep efficiency, and sleep fragmentation. Similar models were used to determine if nighttime sleep characteristics predicted physical activity the following day.
Results
In unadjusted models, greater daily activity counts (B=-.05, p=.005) and more minutes of MVPA (B=-.03, p=.01) were temporally associated with less total sleep time across the week. Greater sleep efficiency was associated with greater daily activity counts (B=.37, p=.01) and more minutes of MVPA (B=.64, p=.009) the following day. Less sleep fragmentation was also associated with greater daily activity counts and more MVPA the following day. Findings were similar after adjustment for age, education, BMI, depressive symptoms, arthritis, and accelerometer wear time.
Conclusions
Few studies have used objective measures to examine the temporal relationship between physical activity and sleep. Notably, these findings suggest that nightly variations in sleep efficiency influence physical activity the following day. Thus, improving overall sleep quality in addition to reducing nightly fluctuations in sleep may be important for encouraging a physically active lifestyle in older women.
doi:10.1249/MSS.0b013e31829e4cea
PMCID: PMC3833970  PMID: 23739529
accelerometer; Actiwatch; objective measurement; sleep efficiency; moderate to vigorous physical activity
20.  Health Characteristics of Postmenopausal Women with Breast Implants 
Plastic and reconstructive surgery  2010;125(3):799-810.
Background
Implant breast augmentation has long been a subject of controversy in both the plastic surgery and mainstream media.
Methods
We evaluated characteristics of women who had breast implant surgery in the Women's Health Initiative observational study (WHI OS) between 1993 and 1998. Most women in this study cohort had breast implant surgery 20 or more years prior to recruitment into the WHI OS. The women who were in the WHI OS who had not undergone breast implant surgery served as the comparison group. There were 86,686 women in the WHI OS who did not have breast implant surgery and an absent history of breast cancer, and 1,257 women who had breast implant surgery and no prior breast cancer.
Results
Total mortality rates were substantially lower among women with breast implant as was incidence of coronary heart disease. Women with breast implants in this study had a lower BMI throughout adult life and were more physically active than control subjects. After adjustment for these variables, differences in total mortality were no longer statistically significant. Women who had breast implants reported overall poorer quality of life and emotional well-being. Among women with breast implant surgery, 7% of deaths were due to suicide (n=3) versus 0.4% (n=20) in controls.
Conclusion
Significant differences in health characteristics and quality of life measures are seen in a cohort of women with breast implants decades following implant surgery. Further longitudinal studies need to focus on both physical and psychological health among women undergoing breast implant surgery.
doi:10.1097/PRS.0b013e3181cb5e29
PMCID: PMC2837521  PMID: 20195108
21.  Pulse wave velocity is associated with β-amyloid deposition in the brains of very elderly adults 
Neurology  2013;81(19):1711-1718.
Objective:
To determine arterial stiffness and β-amyloid (Aβ) deposition in the brain of dementia-free older adults.
Methods:
We studied a cohort of 91 dementia-free participants aged 83–96 years. In 2009, participants completed brain MRI and PET imaging using Pittsburgh compound B (PiB; a marker of amyloid plaques in human brain). In 2011, we measured resting blood pressure (BP), mean arterial pressure (MAP), and arterial stiffness by pulse wave velocity (PWV) in the central, peripheral, and mixed (e.g., brachial ankle PWV [baPWV]) vascular beds, using a noninvasive and automated waveform analyzer.
Results:
A total of 44/91 subjects were Aβ-positive on PET scan. Aβ deposition was associated with mixed PWV, systolic BP, and MAP. One SD increase in baPWV resulted in a 2-fold increase in the odds of being Aβ-positive (p = 0.007). High white matter hyperintensity (WMH) burden was associated with increased central PWV, systolic BP, and MAP. Compared to Aβ-negative individuals with low WMH burden, each SD increase in PWV was associated with a 2-fold to 4-fold increase in the odds of being Aβ-positive and having high WMH.
Conclusions:
Arterial stiffness was associated with Aβ plaque deposition in the brain, independent of BP and APOE ε4 allele. The associations differed by type of brain abnormality and vascular bed measured (e.g., WMH with central stiffness and Aβ deposition and mixed stiffness). Arterial stiffness was highest in individuals with both high Aβ deposition and WMH, which has been suggested to be a “double hit” contributing to the development of symptomatic dementia.
doi:10.1212/01.wnl.0000435301.64776.37
PMCID: PMC3812104  PMID: 24132374
22.  Association of Total Marine Fatty Acids, Eicosapentaenoic and Docosahexaenoic Acids, With Aortic Stiffness in Koreans, Whites, and Japanese Americans 
American Journal of Hypertension  2013;26(11):1321-1327.
BACKGROUND
Few previous studies have reported the association of aortic stiffness with marine n-3 fatty acids (Fas) in the general population. The aim of this study was to determine the combined and independent associations of 2 major marine n-3 FAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), with aortic stiffness evaluated using carotid–femoral pulse wave velocity (cfPWV) in Korean, white, and Japanese American men.
METHODS
A population-based sample of 851 middle-aged men (299 Koreans, 266 whites, and 286 Japanese Americans) was examined for cfPWV during 2002–2006. Serum FAs, including EPA and DHA, were measured as a percentage of total FAs using gas chromatography. Multiple regression analysis was used to examine the association of EPA and DHA with cfPWV after adjusting for blood pressure and other confounders.
RESULTS
Mean EPA and DHA levels were 1.9 (SD = 1.0) and 4.8 (SD = 1.4) for Koreans, 0.8 (SD = 0.6) and 2.4 (SD = 1.2) for whites, and 1.0 (SD = 1.0) and 3.2 (SD = 1.4) for Japanese Americans. Both EPA and DHA were significantly higher in Koreans than in the other 2 groups (P < 0.01). Multiple regression analyses in Koreans showed that cfPWV had a significant inverse association with total marine n-3 FAs and with EPA alone after adjusting for blood pressure and other potential confounders. In contrast, there was no significant association of cfPWV with DHA. Whites and Japanese Americans did not show any significant associations of cfPWV with total marine n-3 FAs, EPA, or DHA.
CONCLUSIONS
High levels of EPA observed in Koreans have an inverse association with aortic stiffness.
doi:10.1093/ajh/hpt107
PMCID: PMC3790451  PMID: 23820020
aortic stiffness; blood pressure; carotid femoral pulse wave velocity; docosahexaenoic acid; eicosapentaenoic acid; fish oil; hypertension.
23.  Do Differences in Risk Factors Explain the Lower Rates of Coronary Heart Disease in Japanese Versus U.S. Women? 
Journal of Women's Health  2013;22(11):966-977.
Abstract
Background
Mortality from coronary heart disease (CHD) in women in Japan is one of the lowest in developed countries. In an attempt to shed some light on possible reasons of lower CHD in women in Japan compared with the United States, we extensively reviewed and analyzed existing national data and recent literature.
Methods
We searched recent epidemiological studies that reported incidence of acute myocardial infarction (AMI) and examined risk factors for CHD in women in Japan. Then, we compared trends in risk factors between women currently aged 50–69 years in Japan and the United States, using national statistics and other available resources.
Results
Recent epidemiological studies have clearly shown that AMI incidence in women in Japan is lower than that reported from other countries, and that lipids, blood pressure (BP), diabetes, smoking, and early menopause are independent risk factors. Comparing trends in risk factors between women in Japan and the United States, current levels of serum total cholesterol are higher in women in Japan and levels have been similar at least since 1990. Levels of BP have been higher in in Japan for the past 3 decades. Prevalence of type 2 diabetes has been similar in Japanese and white women currently aged 60–69 for the past 2 decades. In contrast, rates of cigarette smoking, although low in women in both countries, have been lower in women in Japan.
Conclusions
Differences in risk factors and their trends are unlikely to explain the difference in CHD rates in women in Japan and the United States. Determining the currently unknown factors responsible for low CHD mortality in women in Japan may lead to new strategy for CHD prevention.
doi:10.1089/jwh.2012.4087
PMCID: PMC3820126  PMID: 24073782
24.  The Women’s Health Initiative Hormone Therapy Trials: Update and Overview of Health Outcomes During the Intervention and Post-Stopping Phases 
IMPORTANCE
Menopausal hormone therapy continues in clinical use but questions remain regarding its risks and benefits for chronic disease prevention.
OBJECTIVE
To provide a comprehensive, integrated overview of findings from the two Women’s Health Initiative (WHI) hormone therapy (HT) trials with extended post-intervention follow up.
DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS
27,347 postmenopausal women, age 50–79 years, were enrolled at 40 US centers. Interventions were conjugated equine estrogens (CEE, 0.625 mg/day) with medroxyprogesterone acetate (MPA, 2.5 mg/day) for women with an intact uterus (N = 16,608) and CEE alone for women with hysterectomy (N= 10,739), or their placebos. Intervention continued for 5.6 and 7.2 years (median), respectively, with cumulative follow-up of 13 years through September 30, 2010.
MAIN OUTCOMES AND MEASURES
The primary efficacy and safety outcomes were coronary heart disease (CHD) and invasive breast cancer, respectively. A global index also included stroke, pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture, and deaths. Secondary and quality-of-life outcomes were also assessed.
RESULTS
During the intervention phase for CEE+MPA, the hazard ratio (HR) for CHD was 1.18 (95% confidence interval [CI] 0.95–1.45) and overall risks outweighed benefits, with increases in invasive breast cancer, stroke, pulmonary embolism, and the global index. Other risks included increased dementia (in women >65 years), gallbladder disease, and urinary incontinence, while benefits included decreased hip fractures, diabetes, and vasomotor symptoms. Post-intervention, most risks and benefits dissipated, although some elevation in breast cancer risk persisted (cumulative hazard ratio [HR] =1.28; 95% confidence interval, 1.11–1.48). During intervention for CEE alone, risks and benefits were more balanced, with a HR for CHD of 0.94 (0.78–1.14), increased stroke and venous thrombosis, decreased hip fractures and diabetes, and over cumulative follow-up, decreased breast cancer (HR=0.79 [0.65–0.97]). Neither regimen affected all-cause mortality. With CEE, younger women (50–59 years) had more favorable results for all-cause mortality, myocardial infarction, and the global index (nominal P values for trend by age <0.05), but not for stroke and venous thrombosis. Absolute risks of adverse events (measured by the global index) per 10,000 women per year on CEE+MPA ranged from 12 excess cases for age 50–59 to 38 for age 70–79 and, for CEE, from 19 fewer cases for age 50–59 to 51 excess cases for age 70–79. Results for quality of life outcomes in both trials were mixed.
CONCLUSIONS AND RELEVANCE
Menopausal hormone therapy has a complex pattern of risks and benefits. While appropriate for symptom management in some women, its use for chronic disease prevention is not supported by the WHI randomized trials.
TRIAL REGISTRATION
clinical trials.gov Identifier: NCT00000611
doi:10.1001/jama.2013.278040
PMCID: PMC3963523  PMID: 24084921
25.  Relationship of Hypertension, Blood Pressure, and Blood Pressure Control With White Matter Abnormalities in the Women’s Health Initiative Memory Study (WHIMS)—MRI Trial 
This paper evaluates the relationship of blood pressure (BP) levels at Women’s Health Initiative (WHI) baseline, treatment of hypertension, and white matter abnormalities among women in conjugated equine estrogen (CEE) and medroxyprogesterone acetate and CEE-alone arms. The WHI Memory Study—Magnetic Resonance Imaging (WHIMS-MRI) trial scanned 1424 participants. BP levels at baseline were significantly positively related to abnormal white matter lesion (WML) volumes. Participants treated for hypertension but who had BP ≥140/90 mm Hg had the greatest amount of WML volumes. Women with untreated BP ≥140/90 mm Hg had intermediate WML volumes. Abnormal WML volumes were related to hypertension in most areas of the brain and were greater in the frontal lobe than in the occipital, parietal, or temporal lobes. Level of BP at baseline was strongly related to amount of WML volumes. The results of the study reinforce the relationship of hypertension and BP control and white matter abnormalities in the brain. The evidence to date supports tight control of BP levels, especially beginning at younger and middle age as a possible and perhaps only way to prevent dementia.
doi:10.1111/j.1751-7176.2009.00234.x
PMCID: PMC2864933  PMID: 20433539

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