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Biomedical subjects

Philip Greenland

Publications and source records attributed to Philip Greenland.

At least 19 recordsLinked to original sources
PubMed2026

Plasma proteomics and coronary artery calcium score: synergistic, concordant and contrasting predictions of cardiovascular outcomes in The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Coronary artery calcium (CAC) scores inform subclinical atherosclerotic cardiovascular disease (ASCVD) burden, helping guide preventative treatments. However, prediction of cardiovascular (CV) events by CAC is largely limited to ASCVD outcomes. This study investigated whether a previously validated proteomic test for predicting a broad composite of four-year CV events could enhance the prognostic utility of CAC. METHODS: We used a 27-protein CV risk score (Prot-CVR), derived from ~5,000 SomaScan&#x2122; Assay plasma protein measurements, to predict four-year risk of a composite CV and mortality outcome (myocardial infarction, stroke/TIA, heart failure hospitalization, death) in 2,122 participants with &#x2265;1 CV risk factors from the Multi-Ethnic Study of Atherosclerosis (MESA) observational cohort at exam 5 and compared predictions to CAC Agatston scores. Discriminatory performance was assessed using C-Index and 4-year area under the curve (AUC). Cox Proportional Hazard (CoxPH) ratios were calculated for the composite outcome, ASCVD outcome (myocardial infarction, resuscitated cardiac arrest, stroke, coronary heart disease death), and individual events. Changes in Prot-CVR and CAC scores from baseline to MESA exam 5 (+10-years) in CV event versus event-free participants were assessed using 2-tailed paired t-tests. CoxPH regression models of CV event status distributed by Prot-CVR, CAC, and relevant co-variates were evaluated for performance relative to individual models. RESULTS: Individual Prot-CVR and CAC models predicting the composite outcome had comparable 4-year AUCs, but Prot-CVR had a higher C-index (0.68 (0.65-0.70) versus 0.63 (0.60-0.65), p=0.001) and greater hazard ratios for the composite outcome (p<0.001), death (p<0.001), and heart failure (p=0.015). A combined CoxPH model of Prot-CVR + CAC + Age had a higher 4-year AUC (0.72, p<0.05) and C-Index (0.71, p<0.05) than Prot-CVR or CAC alone. Both Prot-CVR and CAC scores detected an increase in risk prior to an approaching CV event in ~10-year sensitivity-to-change analysis. For 49.6% of MESA population with CAC=0 at baseline, Prot-CVR was greater in composite event versus event free participants at 4 years (0.23 versus 0.15, p=0.006) and full follow-up (0.18 versus 0.13, p<0.001). CONCLUSION: Protein testing complements CAC for CV risk assessment although the improvement is modest. Prot-CVR may resolve which patients with CAC=0 are at heightened CV risk.

Journal Article↗
PubMed2026

Blood Pressure Genetic Risk and Incident Hypertension at 2 to 7 Years Post Partum.

IMPORTANCE: Hypertensive disorders of pregnancy (HDP; ie, preeclampsia/eclampsia and gestational hypertension) are associated with earlier development of chronic hypertension. Whether genetic risk for high systolic blood pressure (SBP) can stratify risk of new-onset hypertension after pregnancy is unclear. OBJECTIVE: To test the association of genetic risk for high SBP with new-onset hypertension at 2 to 7 years after delivery, independent of clinical characteristics and HDP history. DESIGN, SETTING, AND PARTICIPANTS: This was a cohort study of women enrolled during pregnancy between 2010 and 2013 and followed up at 2 to 7 years post partum. Included in the study were genotyped participants without pregestational chronic hypertension in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) Heart Health Study. The setting included 8 US clinical sites. Study data were analyzed from October 2024 to January 2026. EXPOSURES: SBP genetic risk was calculated using a genome-wide SBP polygenic score and categorized as low (bottom quintile), intermediate (quintiles 2-4) or high (top quintile). MAIN OUTCOMES AND MEASURES: The primary outcome was stage 1+ hypertension (&#x2265;130/80 mm Hg or use of antihypertensive medication) at 2 to 7 years post partum. Logistic regression tested the association of SBP genetic risk with development of hypertension, adjusted for sociodemographic factors, prepregnancy diabetes, first-trimester BP, HDP history, and postpartum body mass index (BMI). Key secondary analyses were stratified by HDP history and compared population attributable risk for high SBP genetic risk, HDP history, and postpartum BMI. RESULTS: Among 2852 participants (mean [SD] age, 30.8 [5.5] years; 353 [12.4%] with prior HDP), 509 (17.8%) developed hypertension by 2 to 7 years (mean [SD], 3.2 [0.9] years) after delivery. SBP genetic risk was independently associated with incident hypertension (high vs low SBP genetic risk: adjusted odds ratio [aOR], 1.50; 95% CI, 1.09-2.07; P&#x2009;=&#x2009;.01). In stratified analyses, SBP genetic risk was associated with incident hypertension in those without prior HDP (aOR, 1.25; 95% CI, 1.12-1.40 per SD; P&#x2009;<&#x2009;.001) but not in those with prior HDP (aOR, 1.01; 95% CI, 0.79-1.28 per SD; P&#x2009;=&#x2009;.92; P for interaction&#x2009;=&#x2009;.10). High SBP genetic risk, HDP history, and BMI greater than or equal to 25 (calculated as weight in kilograms divided by height in meters squared) accounted for 4.7%, 10.8%, and 41.5%, respectively, of population attributable risk for hypertension. CONCLUSIONS AND RELEVANCE: Results of this cohort study reveal that higher SBP genetic risk was independently associated with higher risk of developing new-onset hypertension 2 to 7 years after delivery. However, HDP history and elevated BMI were more important contributors to hypertension risk.

Humans↗
PubMed2007

LDL particle subclasses, LDL particle size, and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Previous studies showing that smaller low-density lipoprotein (LDL) size is associated with greater atherosclerotic risk did not adequately control for small and large LDL particle correlation. METHODS AND RESULTS: We studied the association of lipoproteins measured by proton nuclear magnetic resonance spectroscopy with carotid intima-media thickness (IMT) in apparently healthy individuals (N = 5538, 38% White, 28% African American, 22% Hispanic, 12% Chinese). Small and large LDL particle concentrations (LDL-p) were inversely correlated (r = /-0.63, P < 0.0001). Controlling for risk factors but not for LDL subclass correlation, LDL size and small LDL-p separately were associated with IMT (-20.9 and 31.7 microm change in IMT per 1-S.D., respectively, both P < 0.001), but large LDL-p was not (4.9 microm, P = 0.27). When LDL subclasses were included in the same model, large and small LDL-p were both associated with IMT (36.6 and 52.2 microm higher IMT per 1-S.D., respectively, both P < 0.001; 17.7 and 11.6 microm per 100 nmol/L, respectively). LDL size was not significant after accounting for LDL subclasses and risk factors (P = 0.10). CONCLUSION: Both LDL subclasses were significantly associated with subclinical atherosclerosis, with small LDL confounding the association of large LDL with atherosclerosis. Future studies of LDL size should account for the strong inverse correlation of LDL subclasses.

Aged↗
PubMed2006

Cardiovascular disease risk factor knowledge in young adults and 10-year change in risk factors: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

This study's objective was assessment of cardiovascular disease (CVD) risk factor knowledge in young adults, its association with 10-year changes in risk factor levels, and variables related to risk factor knowledge. A total of 4,193 healthy persons (55% female, 48% Black; mean age=30 years) from four urban US communities were queried about risk factor knowledge in 1990-1991 and were reexamined in 2000-2001. Of six risk factors considered (hypertension, hyperlipidemia, smoking, overweight, sedentary lifestyle, and unhealthy diet), participants mentioned a mean of two; more than 65% were not aware of any risk factors, and less than 35% recognized being overweight as a risk factor. After adjustment, variables associated with mentioning more than two CVD risk factors versus one or fewer were Black race (OR=0.52, 95% confidence interval (CI): 0.44, 0.61), having a high school education or less (OR=0.88, 95% CI: 0.80, 0.95), having one or two (vs. zero) risk factors (OR=1.27, 95% CI: 1.05, 1.53), and having three or more (vs. zero) risk factors (OR=1.79, 95% CI: 1.35, 2.38). More knowledge was marginally associated with less increase in body mass index 10 years later (p=0.06) but was unrelated to other risk factor changes. Knowledge of CVD risk factors was very low in these young adults but increased with the presence of risk factors. Knowledge alone did not predict 10-year changes in risk factors.

Adult↗
PubMed2006

Narrative review: Assessment of C-reactive protein in risk prediction for cardiovascular disease.

Some experts propose C-reactive protein (CRP) as a screening tool for prediction of cardiovascular disease (CVD). Many epidemiologic studies show positive associations between elevated CRP levels and incident CVD. Assessment of the value of new prognostic tests, however, must rely on understanding of test characteristics rather than on associations measured by relative risks. In the case of CRP, test characteristics must be judged in the context of currently available CVD risk prediction algorithms. In this review of literature published before January 2006, the authors describe what is known about the additional utility of CRP in risk prediction. They find no definitive evidence that, for most individuals, CRP adds substantial predictive value above that provided by risk estimation using traditional risk factors for CVD. Use of CRP may add to risk estimation in a limited subset of individuals who are at intermediate predicted risk according to the Framingham risk score. The authors propose that many questions still must be addressed before CRP is incorporated into risk prediction algorithms and before universal screening with CRP can be recommended.

Algorithms↗
PubMed2006

Comparison of risk factors for cardiovascular mortality in black and white adults.

BACKGROUND: Recent attention to racial and ethnic disparities in health outcomes highlights the excess coronary heart disease mortality in black patients compared with white patients. We investigated whether traditional cardiovascular disease (CVD) risk factors were similarly associated with CVD mortality in black and white men and women. METHODS: Participants included 3741 black and 33,246 white men and women (44%) without a history of myocardial infarction, aged 18 to 64 years at baseline (1967-1973) from the Chicago Heart Association Detection Project in Industry study. Blood pressure, total cholesterol level, body mass index, cigarette smoking, and physician-diagnosed diabetes were assessed at baseline using standard methods. RESULTS: Through 2002, there were 107, 1586, 177, and 2866 deaths from CVD in black women, white women, black men, and white men, respectively. In general, the magnitude and direction of associations between traditional risk factors and CVD mortality were similar by race. However, in black women the multivariable-adjusted hazard ratio (HR) per 12 mm Hg of diastolic blood pressure was 1.08 (95% confidence interval [CI], 0.90-1.29), whereas it was 1.31 in white women (95% CI, 1.25-1.38). There was no association between higher cholesterol level (per 40 mg/dL [1.04 mmol/L]) and CVD mortality in black men (HR, 0.94; 95% CI, 0.80-1.10), whereas the risk was elevated in white men (HR, 1.21; 95% CI, 1.16-1.26). CONCLUSIONS: Most traditional risk factors demonstrated similar associations with mortality in black and white adults of the same sex. Small differences were primarily in the strength, not the direction, of association.

Adult↗
PubMed2006

Education, 15-year risk factor progression, and coronary artery calcium in young adulthood and early middle age: the Coronary Artery Risk Development in Young Adults study.

CONTEXT: The inverse association between education and cardiovascular disease is well established, but little is known about the relationship between education and subclinical disease, which is free from medical access and treatment-related influences, or about possible mediating pathways for these relationships. OBJECTIVE: To examine the association of education with coronary artery calcium (CAC), an indicator of subclinical atherosclerosis, and cardiovascular risk factors, and their changes as potential mediators. DESIGN, SETTING, AND PARTICIPANTS: A population-based, prospective, observational study (Coronary Artery Risk Development in Young Adults [CARDIA]) of 2913 eligible participants (44.9% black; 53.9% women) recruited from 4 metropolitan areas (Birmingham, Ala; Chicago, Ill; Minneapolis, Minn; and Oakland, Calif) in both the baseline (1985-1986, ages 18-30 years) and year 15 examinations (2000-2001, ages 33-45 years). Education (year 15) was classified into less than high school (n = 128), high school graduate (n = 498), some college (n = 902), college graduate (n = 764), and more than college (n = 621). MAIN OUTCOME MEASURE: Presence of CAC, measured twice by computed tomography (mean total Agatston score >0) at year 15. RESULTS: Overall CAC prevalence in this sample was 9.3%. After adjusting for age, race, and sex, the odds ratios (ORs) for having CAC were 4.14 (95% confidence interval [CI], 2.33-7.35) for less than high school education, 1.89 (95% CI, 1.23-2.91) for high school graduate, 1.47 (95% CI, 0.99-2.19) for some college, and 1.24 (95% CI, 0.84-1.85) for college graduate compared with those participants with more than a college education (P for trend<.001). This was also consistent within each of the 4 race-sex groups. Adjustment for baseline systolic blood pressure, smoking, waist circumference, physical activity, and total cholesterol reduced the ORs to 2.61 (95% CI, 1.40-4.85) for less than high school, 1.38 (95% CI, 0.88-2.17) for high school graduate, 1.17 (95% CI, 0.78-1.77) for some college, and 1.13 (95% CI, 0.76-1.69) for college graduate compared with more than a college education (P for trend = .01), and only slightly attenuated by further adjustment for 15-year changes in risk factors. CONCLUSION: Education was inversely associated with the prevalence of CAC, an association partially explained by baseline risk factors and minimally by 15-year changes in risk factors.

Adult↗
PubMed2006

Statin use and functional decline in patients with and without peripheral arterial disease.

OBJECTIVES: We determined whether statin use (vs. non-use) is associated with less annual decline in lower-extremity functioning in patients with and without lower-extremity peripheral arterial disease (PAD) over three-year follow-up. BACKGROUND: It is unclear whether statin use is associated with less functional decline in patients with PAD. METHODS: Participants included 332 men and women with an ankle brachial index (ABI) <0.90 and 212 with ABI 0.90 to 1.50. Functional outcomes included 6-min walk distance and usual and rapid-pace 4-m walking velocity. A summary performance score combined performance in walking speed, standing balance, and time for five repeated chair rises into an ordinal score ranging from 0 to 12 (12 = best). RESULTS: Adjusting for age, race, gender, comorbidities, education, health insurance, total cholesterol/high-density lipoprotein level, body mass index, pack-years of smoking, leg symptoms, immediately previous year functioning, statin use/non-use, ABI, and change in ABI, the PAD participants using statins had less annual decline in usual-pace walking velocity (0.002 vs. -0.024 m/s/year, p = 0.013), rapid-pace walking velocity (-0.006 vs. -0.042 m/s/year, p = 0.006), 6-min walk performance (-34.5 vs. -57.9 feet/year, p = 0.088), and the summary performance score (-0.152 vs. -0.376, p = 0.067) compared with non-users. These associations were attenuated slightly by additional adjustment for high-sensitivity C-reactive protein levels. Among non-PAD participants, there were no significant associations between statin use and functional decline. CONCLUSIONS: The PAD patients on statins have less annual decline in lower-extremity performance than PAD patients who are not taking statins.

Aged↗
PubMed2006

Low-fat dietary pattern and risk of cardiovascular disease: the Women's Health Initiative Randomized Controlled Dietary Modification Trial.

CONTEXT: Multiple epidemiologic studies and some trials have linked diet with cardiovascular disease (CVD) prevention, but long-term intervention data are needed. OBJECTIVE: To test the hypothesis that a dietary intervention, intended to be low in fat and high in vegetables, fruits, and grains to reduce cancer, would reduce CVD risk. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial of 48,835 postmenopausal women aged 50 to 79 years, of diverse backgrounds and ethnicities, who participated in the Women's Health Initiative Dietary Modification Trial. Women were randomly assigned to an intervention (19,541 [40%]) or comparison group (29,294 [60%]) in a free-living setting. Study enrollment occurred between 1993 and 1998 in 40 US clinical centers; mean follow-up in this analysis was 8.1 years. INTERVENTION: Intensive behavior modification in group and individual sessions designed to reduce total fat intake to 20% of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d. The comparison group received diet-related education materials. MAIN OUTCOME MEASURES: Fatal and nonfatal coronary heart disease (CHD), fatal and nonfatal stroke, and CVD (composite of CHD and stroke). RESULTS: By year 6, mean fat intake decreased by 8.2% of energy intake in the intervention vs the comparison group, with small decreases in saturated (2.9%), monounsaturated (3.3%), and polyunsaturated (1.5%) fat; increases occurred in intakes of vegetables/fruits (1.1 servings/d) and grains (0.5 serving/d). Low-density lipoprotein cholesterol levels, diastolic blood pressure, and factor VIIc levels were significantly reduced by 3.55 mg/dL, 0.31 mm Hg, and 4.29%, respectively; levels of high-density lipoprotein cholesterol, triglycerides, glucose, and insulin did not significantly differ in the intervention vs comparison groups. The numbers who developed CHD, stroke, and CVD (annualized incidence rates) were 1000 (0.63%), 434 (0.28%), and 1357 (0.86%) in the intervention and 1549 (0.65%), 642 (0.27%), and 2088 (0.88%) in the comparison group. The diet had no significant effects on incidence of CHD (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.90-1.06), stroke (HR, 1.02; 95% CI, 0.90-1.15), or CVD (HR, 0.98; 95% CI, 0.92-1.05). Excluding participants with baseline CVD (3.4%), the HRs (95% CIs) for CHD and stroke were 0.94 (0.86-1.02) and 1.02 (0.90-1.17), respectively. Trends toward greater reductions in CHD risk were observed in those with lower intakes of saturated fat or trans fat or higher intakes of vegetables/fruits. CONCLUSIONS: Over a mean of 8.1 years, a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT00000611.

Aged↗
PubMed2006

Cutaneous melanoma in postmenopausal women after nonmelanoma skin carcinoma: the Women's Health Initiative Observational Study.

BACKGROUND: An elevated risk for cutaneous melanoma has been reported in individuals with nonmelanoma skin carcinoma (NMSC), but to the authors' knowledge, this association has not been prospectively studied in a large, multigeographic population of postmenopausal women. METHODS: The association between NMSC and the incidence of cutaneous melanoma was assessed in the Women's Health Initiative Observational Study involving 67,030 non-Hispanic white postmenopausal women ages 50-79 years and who were free of prior other cancers at baseline. Cancer history, demographics, and previous and current risk exposures were determined by questionnaires at baseline and follow-up. Participants' reports of incident cutaneous melanoma collected annually were confirmed by physician review of medical records. Cox proportional hazards analyses were used to assess the relation of prior NMSC with incident cutaneous melanoma. RESULTS: In age-adjusted analysis, women with a history of NMSC but no other malignancy (n = 5552) were found to be 2.41 times more likely to develop cutaneous melanoma over a mean 6.5 years compared with women who had no history of NMSC (95% confidence interval [95% CI], 1.82-3.20). In a multivariate analysis, women with a history of NMSC and no other cancer history at baseline were 1.70 times more likely to develop cutaneous melanoma compared with women without NMSC (95% CI, 1.18-2.44). CONCLUSION: The results of the current study provide evidence and further defines the magnitude of increased risk for cutaneous melanoma in postmenopausal non-Hispanic white women with a history of NMSC.

Aged↗
PubMed2006

Midlife body mass index and hospitalization and mortality in older age.

CONTEXT: Abundant evidence links overweight and obesity with impaired health. However, controversies persist as to whether overweight and obesity have additional impact on cardiovascular outcomes independent of their strong associations with established coronary risk factors, eg, high blood pressure and high cholesterol level. OBJECTIVE: To assess the relation of midlife body mass index with morbidity and mortality outcomes in older age among individuals without and with other major risk factors at baseline. DESIGN: Chicago Heart Association Detection Project in Industry study, a prospective study with baseline (1967-1973) cardiovascular risk classified as low risk (blood pressure < or =120/< or =80 mm Hg, serum total cholesterol level <200 mg/dL [5.2 mmol/L], and not currently smoking); moderate risk (nonsmoking and systolic blood pressure 121-139 mm Hg, diastolic blood pressure 81-89 mm Hg, and/or total cholesterol level 200-239 mg/dL [5.2-6.2 mmol/L]); or having any 1, any 2, or all 3 of the following risk factors: blood pressure > or =140/90 mm Hg, total cholesterol level > or =240 mg/dL (6.2 mmol/L), and current cigarette smoking. Body mass index was classified as normal weight (18.5-24.9), overweight (25.0-29.9), or obese (> or =30). Mean follow-up was 32 years. SETTING AND PARTICIPANTS: Participants were 17,643 men and women aged 31 through 64 years, recruited from Chicago-area companies or organizations and free of coronary heart disease (CHD), diabetes, or major electrocardiographic abnormalities at baseline. MAIN OUTCOME MEASURES: Hospitalization and mortality from CHD, cardiovascular disease, or diabetes, beginning at age 65 years. RESULTS: In multivariable analyses that included adjustment for systolic blood pressure and total cholesterol level, the odds ratio (95% confidence interval) for CHD death for obese participants compared with those of normal weight in the same risk category was 1.43 (0.33-6.25) for low risk and 2.07 (1.29-3.31) for moderate risk; for CHD hospitalization, the corresponding results were 4.25 (1.57-11.5) for low risk and 2.04 (1.29-3.24) for moderate risk. Results were similar for other risk groups and for cardiovascular disease, but stronger for diabetes (eg, low risk: 11.0 [2.21-54.5] for mortality and 7.84 [3.95-15.6] for hospitalization). CONCLUSION: For individuals with no cardiovascular risk factors as well as for those with 1 or more risk factors, those who are obese in middle age have a higher risk of hospitalization and mortality from CHD, cardiovascular disease, and diabetes in older age than those who are normal weight.

Adult↗