@article {1145, title = {Combined association of lipids and blood pressure in relation to incident cardiovascular disease in the elderly: the cardiovascular health study.}, journal = {Am J Hypertens}, volume = {23}, year = {2010}, month = {2010 Feb}, pages = {161-7}, abstract = {

BACKGROUND: Hypertension and dyslipidemia are highly prevalent in the elderly. We studied the combined impact of both conditions on cardiovascular disease (CVD) events.

METHODS: We studied 4,311 participants aged 65-98 (61.2\% female) from the Cardiovascular Health Study (CHS), a longitudinal epidemiologic study, with no prior CVD. We evaluated the relation of low-density lipoprotein (LDL), high-density lipoprotein (HDL), or non-HDL-cholesterol combined with blood pressure (BP) categories to incident CVD-including coronary heart disease (CHD) (angina, myocardial infarction (MI), angioplasty, coronary bypass surgery, or CHD death), stroke, claudication, and CVD death over 15 years.

RESULTS: CVD incidence (per 1,000 person years) ranged from 38.4 when BP <120/80 mm Hg and LDL-C <100 mg/dl to 94.8 when BP >or=160/100 mm Hg and LDL-C >or=160 mg/dl, and from 28.9 when BP <120/80 mm Hg and HDL >60 mg/dl to 87.1 for a BP >or=160/100 and HDL-C <40 mg/dl. Compared with those with BP <120/80 mm Hg with either LDL-C <100 mg/dl or HDL-C >60 mg/dl, hazard ratios (HRs) for CVD events were 2.1 when BP >or=160/100 mm Hg and LDL-C >or=160 mg/dl and 2.1 when BP >or=160/100 and HDL-C <40 mg/dl (all P < 0.01), with similar results for non-HDL-C. Elevated BP was associated with increased risk across all lipid levels. Increased LDL-C added risk mainly when BP <140/90 mm Hg, but lower HDL-C also predicted CVD in those with higher BP.

CONCLUSION: Increased BP confers increased risks for CVD in elderly persons across all lipid levels. Although increased LDL-C added risk mainly when BP <140/90 mm Hg, low HDL-C added risk also in those with hypertension. These results document the importance of combined hypertension and dyslipidemia.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Blood Pressure, Cardiovascular Diseases, Cholesterol, HDL, Cholesterol, LDL, Diabetes Mellitus, Female, Health Surveys, Humans, Likelihood Functions, Lipids, Male, Proportional Hazards Models, Sex Factors, Smoking, Socioeconomic Factors, United States}, issn = {1941-7225}, doi = {10.1038/ajh.2009.216}, author = {Wong, Nathan D and Lopez, Victor A and Roberts, Craig S and Solomon, Henry A and Burke, Gregory L and Kuller, Lewis and Tracy, Russell and Yanez, David and Psaty, Bruce M} } @article {6167, title = {Impact of inflammatory biomarkers on relation of high density lipoprotein-cholesterol with incident coronary heart disease: cardiovascular Health Study.}, journal = {Atherosclerosis}, volume = {231}, year = {2013}, month = {2013 Dec}, pages = {246-51}, abstract = {

BACKGROUND: Inflammatory factors and low HDL-C relate to CHD risk, but whether inflammation attenuates any protective association of high HDL-C is unknown.

OBJECTIVE: Investigate inflammatory markers{\textquoteright} individual and collective impact on the association of HDL-C with incident coronary heart disease (CHD).

METHODS: In 3888 older adults without known cardiovascular disease (CVD), we examined if the inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), and lipoprotein-associated phospholipase A2 (Lp-PLA$_{2}$) modify the relation of HDL-C with CHD. HDL-C, CRP, IL-6, and Lp-PLA$_{2}$ values were grouped as using gender-specific tertiles. Also, an inflammation index of z-score sums for CRP, IL-6, and Lp-PLA$_{2}$ was categorized into tertiles. We calculated CHD incidence for each HDL-C/inflammation group and performed Cox regression, adjusted for standard CVD risk factors and triglycerides to examine the relationship of combined HDL-C-inflammation groups with incident events.

RESULTS: CHD incidence (per 1000 person years) was higher for higher levels of CRP, IL-6, and the index, and lower for higher levels of HDL-C. Compared to high HDL-C/low-inflammation categories (referent), adjusted HRs for incident CHD were increased for those with high HDL-C and high CRP (HR = 1.50, p < 0.01) or highest IL-6 tertile (HR = 1.40, p < 0.05), but not with highest Lp-PLA$_{2}$ tertile. Higher CHD incidence was similarly seen for those with intermediate or low HDL-C accompanied by high CRP, high IL-6, or a high inflammatory index.

CONCLUSION: The protective relation of high HDL-C for incident CHD appears to be attenuated by greater inflammation.

}, keywords = {1-Alkyl-2-acetylglycerophosphocholine Esterase, African Americans, Aged, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Cholesterol, HDL, Coronary Disease, European Continental Ancestry Group, Female, Humans, Incidence, Inflammation, Interleukin-6, Male, Middle Aged, Proportional Hazards Models, Prospective Studies, Risk Factors}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2013.08.036}, author = {Tehrani, David M and Gardin, Julius M and Yanez, David and Hirsch, Calvin H and Lloyd-Jones, Donald M and Stein, Phyllis K and Wong, Nathan D} } @article {6564, title = {What do carotid intima-media thickness and plaque add to the prediction of stroke and cardiovascular disease risk in older adults? The cardiovascular health study.}, journal = {J Am Soc Echocardiogr}, volume = {27}, year = {2014}, month = {2014 Sep}, pages = {998-1005.e2}, abstract = {

BACKGROUND: The aim of this study was to evaluate whether the addition of ultrasound carotid intima-media thickness (CIMT) measurements and risk categories of plaque help predict incident stroke and cardiovascular disease (CVD) in older adults.

METHODS: Carotid ultrasound studies were recorded in the multicenter Cardiovascular Health Study. CVD was defined as coronary heart disease plus heart failure plus stroke. Ten-year risk prediction Cox proportional-hazards models for stroke and CVD were calculated using Cardiovascular Health Study-specific coefficients for Framingham risk score factors. Categories of CIMT and CIMT plus plaque were added to Framingham risk score prediction models, and categorical net reclassification improvement (NRI) and Harrell{\textquoteright}s c-statistic were calculated.

RESULTS: In 4,384 Cardiovascular Health Study participants (61\% women, 14\% black; mean baseline age, 72~{\textpm}~5 years) without CVD at baseline, higher CIMT category and the presence of plaque were both associated with higher incidence rates for stroke and CVD. The addition of CIMT improved the ability of Framingham risk score-type risk models to discriminate cases from noncases of incident stroke and CVD (NRI~= 0.062, P~=~.015, and NRI~= 0.027, P < .001, respectively), with no further improvement by adding plaque. For both outcomes, NRI was driven by down-classifying those without incident disease. Although the addition of plaque to CIMT~did not result in a significant NRI for either outcome, it was significant among those without incident disease.

CONCLUSIONS: In older adults, the addition of CIMT modestly improves 10-year risk prediction for stroke and CVD beyond a traditional risk factor model, mainly by down-classifying risk in those without stroke or CVD; the addition of plaque to CIMT adds no statistical benefit in the overall cohort, although there is evidence of down-classification in those without events.

}, keywords = {Aged, Cardiovascular Diseases, Carotid Intima-Media Thickness, Carotid Stenosis, Comorbidity, Female, Humans, Incidence, Longitudinal Studies, Male, Reproducibility of Results, Risk Factors, Sensitivity and Specificity, Stroke, Survival Rate}, issn = {1097-6795}, doi = {10.1016/j.echo.2014.06.013}, author = {Gardin, Julius M and Bartz, Traci M and Polak, Joseph F and O{\textquoteright}Leary, Daniel H and Wong, Nathan D} } @article {6826, title = {LV Mass as a Predictor of CVD Events in~Older Adults With and Without Metabolic Syndrome and Diabetes.}, journal = {JACC Cardiovasc Imaging}, volume = {8}, year = {2015}, month = {2015 Sep}, pages = {1007-15}, abstract = {

OBJECTIVES: The purpose of this study was to examine the prognostic significance of left ventricular (LV) mass for cardiovascular disease (CVD) events in older adults with and without metabolic syndrome (MetS) and diabetes mellitus (DM).

BACKGROUND: MetS and DM are associated with increased CVD risk, but it is unclear in these groups whether subclinical CVD as shown by increased LV mass improves risk prediction compared to standard risk factors in older individuals.

METHODS: We studied 3,724 adults (mean 72.4 {\textpm} 5.4 years of age, 61.0\% female, 4.4\% African-American) from the Cardiovascular Health Study who had MetS but not DM or had DM alone or had neither condition. Cox regression was used to examine the association of LV mass, (alone and indexed by height and body surface area [BSA]) as determined by echocardiography, with CVD events, including coronary heart disease (CHD), stroke, heart failure (HF), and CVD death, as well as total mortality. We also assessed the added prediction, discriminative value, and net reclassification improvement (NRI) for clinical utility of LV mass compared to standard risk factors.

RESULTS: Over a mean follow-up of 14.2 {\textpm} 6.3 years, 2,180 subjects experienced CVD events, including 986 CVD deaths. After adjustment for age, sex and standard risk factors, LV mass was positively associated with CVD events in those with MetS (hazard ratio [HR]: 1.4, p~< 0.001) and without MetS (HR: 1.4, p~< 0.001), but not DM (HR: 1.0, p~= 0.62), with similar findings for LV mass indexed for height or BSA. Adding LV mass to standard risk factors moderately improved the prediction accuracy in the overall sample and MetS group from changes in C-statistics (p~< 0.05). Categorical-free net reclassification improvement increased significantly by 17\% to 19\% in those with MetS. Findings were comparable for CHD, CVD mortality, and total mortality.

CONCLUSIONS: LV mass is associated with increased CVD risk and provides modest added prediction and clinical utility compared to standard risk factors in older persons with and without MetS but not with DM.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Comorbidity, Diabetes Mellitus, Female, Heart Ventricles, Humans, Hypertrophy, Left Ventricular, Logistic Models, Male, Metabolic Syndrome X, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States}, issn = {1876-7591}, doi = {10.1016/j.jcmg.2015.04.019}, author = {Hoang, Khiet and Zhao, Yanglu and Gardin, Julius M and Carnethon, Mercedes and Mukamal, Ken and Yanez, David and Wong, Nathan D} } @article {7117, title = {Cardiovascular Disease, Mortality Risk, and Healthcare Costs by Lipoprotein(a) Levels According to Low-density Lipoprotein Cholesterol Levels in Older High-risk Adults.}, journal = {Clin Cardiol}, volume = {39}, year = {2016}, month = {2016 Jul}, pages = {413-20}, abstract = {

BACKGROUND: The value of lipoprotein(a) (Lp[a]) for predicting cardiovascular disease (CVD) across low-density lipoprotein cholesterol (LDL-C) is uncertain.

HYPOTHESIS: In older high-risk adults, higher LDL and Lp(a) combined would be associated with higher CVD risk and more healthcare costs.

METHODS: We included 3251 high-risk subjects (prior CVD, diabetes, or 10-year Framingham CVD risk >20\%) age >=65 years from the Cardiovascular Health Study and examined the relation of Lp(a) tertiles with incident CVD, coronary heart disease (CHD), and all-cause mortality within LDL-C strata (spanning <70 mg/dL to >=160 mg/dL). We also examined 1-year all-cause and CVD healthcare costs from Medicare claims.

RESULTS: Over a 22.5-year follow-up, higher Lp(a) levels predicted CVD and total mortality (both standardized hazard ratio [HR]: 1.06, P < 0.01), whereas higher LDL-C levels predicted higher CHD (standardized HR: 1.09, P < 0.01) but lower total mortality (standardized HR: 0.94, P < 0.001). Adjusted HRs in the highest (vs lowest) tertile of Lp(a) level were 1.95 (P = 0.06) for CVD events and 2.68 (P = 0.03) for CHD events when LDL-C was <70 mg/dL. One-year all-cause healthcare costs were increased for Lp(a) ($771 per SD of 56 {\textmu}g/mL [P = 0.03], $1976 for Lp(a) 25-64 {\textmu}g/mL vs <25 {\textmu}g/mL [P = 0.02], and $1648 for Lp(a) >=65 {\textmu}g/mL vs <25 {\textmu}g/mL [P = 0.054]) but not LDL-C.

CONCLUSIONS: In older high-risk adults, increased Lp(a) levels were associated with higher CVD risk, especially in those with LDL-C <70 mg/dL, and with higher healthcare costs.

}, issn = {1932-8737}, doi = {10.1002/clc.22546}, author = {Zhao, Yanglu and Delaney, Joseph A and Quek, Ruben G W and Gardin, Julius M and Hirsch, Calvin H and Gandra, Shravanthi R and Wong, Nathan D} } @article {7799, title = {Impact of lung-function measures on cardiovascular disease events in older adults with metabolic syndrome and diabetes.}, journal = {Clin Cardiol}, volume = {41}, year = {2018}, month = {2018 Jul}, pages = {959-965}, abstract = {

BACKGROUND: Individuals with metabolic syndrome (MetS) and diabetes (DM) are more likely to have decreased lung function and are at greater risk of cardiovascular disease (CVD).

HYPOTHESIS: Lung-function measures can predict CVD events in older persons with MetS, DM, and neither condition.

METHODS: We followed 4114 participants age >= 65 years with and without MetS or DM in the Cardiovascular Health Study. Cox regression examined the association of forced vital capacity (FVC) and 1-second forced expiratory volume (FEV ; percent of predicted values) with incident coronary heart disease and CVD events over 12.9 years.

RESULTS: DM was present in 537 (13.1\%) and MetS in 1277 (31.0\%) participants. Comparing fourth vs first quartiles for FVC, risk of CVD events was 16\% (HR: 0.84, 95\% CI: 0.59-1.18), 23\% (HR: 0.77, 95\% CI: 0.60-0.99), and 30\% (HR: 0.70, 95\% CI: 0.58-0.84) lower in DM, MetS, and neither disease groups, respectively. For FEV , CVD risk was lower by 2\% (HR: 0.98, 95\% CI: 0.70-1.37), 26\% (HR: 0.74, 95\% CI: 0.59-0.93), and 31\% (HR: 0.69, 95\% CI: 0.57-0.82) in DM. Findings were strongest for predicting congestive heart failure (CHF) in all disease groups. C-statistics increased significantly with addition of FEV or FVC over risk factors for CVD and CHF among those with neither MetS nor DM.

CONCLUSIONS: FEV and FVC are inversely related to CVD in older adults with and without MetS, but not DM (except for CHF); however, their value in incremental risk prediction beyond standard risk factors is limited mainly to metabolically healthier persons.

}, issn = {1932-8737}, doi = {10.1002/clc.22985}, author = {Lee, Hwa Mu and Zhao, Yanglu and Liu, Michael A and Yanez, David and Carnethon, Mercedes and Graham Barr, R and Wong, Nathan D} } @article {8108, title = {Trends in Blood Pressure and High-Sensitivity Cardiac Troponin-T with Cardiovascular Disease: The Cardiovascular Health Study.}, journal = {Am J Hypertens}, year = {2019}, month = {2019 Jun 21}, abstract = {

BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) is individually associated with incident hypertension (HTN) and cardiovascular disease (CVD) events. We hypothesize that the increases in hs-cTnT with increases in blood pressure will be related to higher incidence of CVD.

METHODS: The Cardiovascular Health Study is a longitudinal cohort of older adults. Those with hs-cTnT data and CVD risk factors at baseline and follow-up (2-3 years later) were stratified based on systolic blood pressure (SBP) (optimal: <120 mmHg, intermediate: 120-139 mmHg, elevated: >=140 mmHg) and hs-cTnT (undetectable: <5 ng/L, detectable: 5-13 ng/L, elevated: >=14 ng/L) categories. SBP and hs-cTnT were classified as increased or decreased if they changed categories between exams, and stable if they did not. Cox regression evaluated incident CVD events over an average 9 year follow-up.

RESULTS: Among 2219 adults, 510 (23.0 \%) had decreased hs-cTnT, 1,279 (57.6 \%) had stable hs-cTnT, and 430 (19.4 \%) had increased hs-cTnT. Those with increased hs-cTnT had a higher CVD risk with stable SBP (HR: 1.28 [1.04-1.57], p=0.02) or decreased SBP (HR: 1.57 [1.08-2.28], p=0.02) compared to those within the same SBP group but a stable hs-cTnT. In those with lower SBP at follow-up, there was an inverse relation between DBP and risk of CVD events in those with increased hs-cTnT (HR: 0.44 per 10 mmHg increase, p<0.01).

CONCLUSION: An increase in hs-cTnT over time is associated with a higher risk of CVD even when the blood pressure is stable or decreases over time.

}, issn = {1941-7225}, doi = {10.1093/ajh/hpz102}, author = {Tehrani, David M and Fan, Wenjun and Nambi, Vijay and Gardin, Julius and Hirsch, Calvin H and Amsterdam, Ezra and deFilippi, Christopher R and Polonsky, Tamar and Wong, Nathan D} } @article {8499, title = {Pre-diabetes, diabetes and predictors of incident angina among older women and men in the Cardiovascular Health Study.}, journal = {Diab Vasc Dis Res}, volume = {17}, year = {2020}, month = {2020 Jan-Feb}, pages = {1479164119888476}, abstract = {

Diabetes mellitus and angina pectoris are important conditions in older persons. The utility of pre-diabetes mellitus, diabetes mellitus and other risk factors as predictors of incident angina pectoris among older adults has not been characterized. We examined incident angina pectoris rates by sex and diabetes mellitus status in 4511 adults aged ⩾65 years without coronary heart disease at baseline from the Cardiovascular Health Study. Cox regression examined predictors of incident angina pectoris, including pre-diabetes mellitus or diabetes mellitus adjusted for sociodemographic characteristics and other risk factors, over 12.2 {\textpm} 6.9 years of follow-up. Overall, 39.1\% of participants had pre-diabetes mellitus, 14.0\% had diabetes mellitus and 532 (11.8\%) had incident angina pectoris. Incident angina pectoris rates per 1000 person-years in those with neither condition, pre-diabetes mellitus, and diabetes mellitus were 7.9, 9.0 and 12.3 in women and 10.3, 11.2 and 14.5 in men, respectively. Pre-diabetes mellitus and diabetes mellitus were not independently associated with incident AP; however, key predictors of AP were male sex, low-density lipoprotein-cholesterol, triglycerides, systolic blood pressure, antihypertensive medication and difficulty performing at least one instrumental activity of daily living (all < 0.05 to < 0.01). In our cohort of older adult participants, while the incidence of AP is greater in those with diabetes mellitus, neither diabetes mellitus nor pre-diabetes mellitus independently predicted incident angina pectoris.

}, keywords = {Age Factors, Aged, Angina Pectoris, Diabetes Mellitus, Female, Humans, Incidence, Male, Prediabetic State, Prognosis, Prospective Studies, Risk Assessment, Risk Factors, Sex Factors, Time Factors, United States}, issn = {1752-8984}, doi = {10.1177/1479164119888476}, author = {Mathenge, Njambi and Fan, Wenjun and Wong, Nathan D and Hirsch, Calvin and Delaney, Chris Joseph and Amsterdam, Ezra A and Koch, Bruce and Calara, Rico and Gardin, Julius M} }