Browsing by Author "Sacco, Ralph L"

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    Carotid intima-media thickness progression and risk of vascular events in people with diabetes: results from the PROG-IMT collaboration.
    (Diabetes care, 2015-10) Lorenz, Matthias W; Price, Jackie F; Robertson, Christine; Bots, Michiel L; Polak, Joseph F; Poppert, Holger; Kavousi, Maryam; Dörr, Marcus; Stensland, Eva; Ducimetiere, Pierre; Ronkainen, Kimmo; Kiechl, Stefan; Sitzer, Matthias; Rundek, Tatjana; Lind, Lars; Liu, Jing; Bergström, Göran; Grigore, Liliana; Bokemark, Lena; Friera, Alfonsa; Yanez, David; Bickel, Horst; Ikram, M Arfan; Völzke, Henry; Johnsen, Stein Harald; Empana, Jean Philippe; Tuomainen, Tomi-Pekka; Willeit, Peter; Steinmetz, Helmuth; Desvarieux, Moise; Xie, Wuxiang; Schmidt, Caroline; Norata, Giuseppe D; Suarez, Carmen; Sander, Dirk; Hofman, Albert; Schminke, Ulf; Mathiesen, Ellisiv; Plichart, Matthieu; Kauhanen, Jussi; Willeit, Johann; Sacco, Ralph L; McLachlan, Stela; Zhao, Dong; Fagerberg, Björn; Catapano, Alberico L; Gabriel, Rafael; Franco, Oscar H; Bülbül, Alpaslan; Scheckenbach, Frank; Pflug, Anja; Gao, Lu; Thompson, Simon G

    Objective

    Carotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes.

    Research design and methods

    In a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33-92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima-media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis.

    Results

    Average mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12-1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between -0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91-1.08).

    Conclusions

    Despite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes.
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    Correction: Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration.
    (PloS one, 2018-01) Lorenz, Matthias W; Gao, Lu; Ziegelbauer, Kathrin; Norata, Giuseppe Danilo; Empana, Jean Philippe; Schmidtmann, Irene; Lin, Hung-Ju; McLachlan, Stela; Bokemark, Lena; Ronkainen, Kimmo; Amato, Mauro; Schminke, Ulf; Srinivasan, Sathanur R; Lind, Lars; Okazaki, Shuhei; Stehouwer, Coen DA; Willeit, Peter; Polak, Joseph F; Steinmetz, Helmuth; Sander, Dirk; Poppert, Holger; Desvarieux, Moise; Ikram, M Arfan; Johnsen, Stein Harald; Staub, Daniel; Sirtori, Cesare R; Iglseder, Bernhard; Beloqui, Oscar; Engström, Gunnar; Friera, Alfonso; Rozza, Francesco; Xie, Wuxiang; Parraga, Grace; Grigore, Liliana; Plichart, Matthieu; Blankenberg, Stefan; Su, Ta-Chen; Schmidt, Caroline; Tuomainen, Tomi-Pekka; Veglia, Fabrizio; Völzke, Henry; Nijpels, Giel; Willeit, Johann; Sacco, Ralph L; Franco, Oscar H; Uthoff, Heiko; Hedblad, Bo; Suarez, Carmen; Izzo, Raffaele; Zhao, Dong; Wannarong, Thapat; Catapano, Alberico; Ducimetiere, Pierre; Espinola-Klein, Christine; Chien, Kuo-Liong; Price, Jackie F; Bergström, Göran; Kauhanen, Jussi; Tremoli, Elena; Dörr, Marcus; Berenson, Gerald; Kitagawa, Kazuo; Dekker, Jacqueline M; Kiechl, Stefan; Sitzer, Matthias; Bickel, Horst; Rundek, Tatjana; Hofman, Albert; Mathiesen, Ellisiv B; Castelnuovo, Samuela; Landecho, Manuel F; Rosvall, Maria; Gabriel, Rafael; de Luca, Nicola; Liu, Jing; Baldassarre, Damiano; Kavousi, Maryam; de Groot, Eric; Bots, Michiel L; Yanez, David N; Thompson, Simon G; PROG-IMT study group
    [This corrects the article DOI: 10.1371/journal.pone.0191172.].
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    Creatinine- versus cystatin C-based renal function assessment in the Northern Manhattan Study.
    (PloS one, 2018-01) Husain, S Ali; Willey, Joshua Z; Park Moon, Yeseon; Elkind, Mitchell SV; Sacco, Ralph L; Wolf, Myles; Cheung, Ken; Wright, Clinton B; Mohan, Sumit
    BACKGROUND:Accurate glomerular filtration rate estimation informs drug dosing and risk stratification. Body composition heterogeneity influences creatinine production and the precision of creatinine-based estimated glomerular filtration rate (eGFRcr) in the elderly. We compared chronic kidney disease (CKD) categorization using eGFRcr and cystatin C-based estimated GFR (eGFRcys) in an elderly, racially/ethnically diverse cohort to determine their concordance. METHODS:The Northern Manhattan Study (NOMAS) is a predominantly elderly, multi-ethnic cohort with a primary aim to study cardiovascular disease epidemiology. We included participants with concurrently measured creatinine and cystatin C. eGFRcr was calculated using the CKD-EPI 2009 equation. eGFRcys was calculated using the CKD-EPI 2012 equation. Logistic regression was used to estimate odds ratios and 95% confidence intervals of factors associated with reclassification from eGFRcr≥60ml/min/1.73m2 to eGFRcys<60ml/min/1.73m2. RESULTS:Participants (n = 2988, mean age 69±10yrs) were predominantly Hispanic, female, and overweight/obese. eGFRcys was lower than eGFRcr by mean 23mL/min/1.73m2. 51% of participants' CKD status was discordant, and only 28% maintained the same CKD stage by both measures. Most participants (78%) had eGFRcr≥60mL/min/1.73m2; among these, 64% had eGFRcys<60mL/min/1.73m2. Among participants with eGFRcr≥60mL/min/1.73m2, eGFRcys-based reclassification was more likely in those with age >65 years, obesity, current smoking, white race, and female sex. CONCLUSIONS:In a large, multiethnic, elderly cohort, we found a highly discrepant prevalence of CKD with eGFRcys versus eGFRcr. Determining the optimal method to estimate GFR in elderly populations needs urgent further study to improve risk stratification and drug dosing.
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    Functional status at 30 and 90 days after mild ischaemic stroke.
    (Stroke and vascular neurology, 2022-04) Gardener, Hannah; Romano, Leo A; Smith, Eric E; Campo-Bustillo, Iszet; Khan, Yosef; Tai, Sofie; Riley, Nikesha; Sacco, Ralph L; Khatri, Pooja; Alger, Heather M; Mac Grory, Brian; Gulati, Deepak; Sangha, Navdeep S; Olds, Karin E; Benesch, Curtis G; Kelly, Adam G; Brehaut, Scott S; Kansara, Amit C; Schwamm, Lee H; Romano, Jose G

    Background/objective

    This study compares the global disability status of patients who had a mild ischaemic stroke at 30 and 90 days poststroke, as measured by the modified Rankin Scale (mRS), and identifies predictors of change in disability status between 30 and 90 days.

    Methods

    The study population included 1339 patients who had a ischaemic stroke enrolled in the Mild and Rapidly Improving Stroke Study with National Institutes of Health (NIH) stroke score 0-5 and mRS measurements at 30 and 90 days. Outcomes were (1) Improvement defined as having mRS >1 at 30 days and mRS 0-1 at 90 days OR mRS >2 at 30 days and mRS 0-2 at 90 days and (2) Worsening defined as an increase of ≥2 points or a worsening from mRS of 1 at 30 days to 2 at 90 days. Demographic and clinical characteristics at hospital arrival were abstracted from medical records, and regression models were used to identify predictors of functional improvement and decline from 30 to 90 days post-stroke. Significant predictors were mutually adjusted in multivariable models that also included age and stroke severity.

    Results

    Fifty-seven per cent of study participants had no change in mRS value from 30 to 90 days. Overall, there was moderate agreement in mRS between the two time points (weighted kappa=0.59 (95% CI 0.56 to 0.62)). However, worsening on the mRS was observed in 7.54% of the study population from 30 to 90 days, and 17.33% improved. Participants of older age (per year OR 1.02, 95% CI 1.00 to 1.03), greater stroke severity (per NIH Stroke Scale (NIHSS) point at admission OR 1.17, 95% CI 1.03 to 1.34), and those with no alteplase treatment (OR 1.72, 95% CI 1.11 to 2.69) were more likely to show functional decline after mutual adjustment.

    Discussion

    A quarter of all mild ischaemic stroke participants exhibited functional changes between 30 and 90 days, suggesting that the 30-day outcome may insufficiently represent long-term recovery in mild stroke and longer follow-up may be clinically necessary.

    Trial registration number

    NCT02072681.
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    Inflammatory markers and extent and progression of early atherosclerosis: Meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration.
    (European journal of preventive cardiology, 2016-01) Willeit, Peter; Thompson, Simon G; Agewall, Stefan; Bergström, Göran; Bickel, Horst; Catapano, Alberico L; Chien, Kuo-Liong; de Groot, Eric; Empana, Jean-Philippe; Etgen, Thorleif; Franco, Oscar H; Iglseder, Bernhard; Johnsen, Stein H; Kavousi, Maryam; Lind, Lars; Liu, Jing; Mathiesen, Ellisiv B; Norata, Giuseppe D; Olsen, Michael H; Papagianni, Aikaterini; Poppert, Holger; Price, Jackie F; Sacco, Ralph L; Yanez, David N; Zhao, Dong; Schminke, Ulf; Bülbül, Alpaslan; Polak, Joseph F; Sitzer, Matthias; Hofman, Albert; Grigore, Liliana; Dörr, Marcus; Su, Ta-Chen; Ducimetière, Pierre; Xie, Wuxiang; Ronkainen, Kimmo; Kiechl, Stefan; Rundek, Tatjana; Robertson, Christine; Fagerberg, Björn; Bokemark, Lena; Steinmetz, Helmuth; Ikram, M Arfan; Völzke, Henry; Lin, Hung-Ju; Plichart, Matthieu; Tuomainen, Tomi-Pekka; Desvarieux, Moise; McLachlan, Stela; Schmidt, Caroline; Kauhanen, Jussi; Willeit, Johann; Lorenz, Matthias W; Sander, Dirk; PROG-IMT study group

    Background

    Large-scale epidemiological evidence on the role of inflammation in early atherosclerosis, assessed by carotid ultrasound, is lacking. We aimed to quantify cross-sectional and longitudinal associations of inflammatory markers with common-carotid-artery intima-media thickness (CCA-IMT) in the general population.

    Methods

    Information on high-sensitivity C-reactive protein, fibrinogen, leucocyte count and CCA-IMT was available in 20 prospective cohort studies of the PROG-IMT collaboration involving 49,097 participants free of pre-existing cardiovascular disease. Estimates of associations were calculated within each study and then combined using random-effects meta-analyses.

    Results

    Mean baseline CCA-IMT amounted to 0.74 mm (SD = 0.18) and mean CCA-IMT progression over a mean of 3.9 years to 0.011 mm/year (SD = 0.039). Cross-sectional analyses showed positive linear associations between inflammatory markers and baseline CCA-IMT. After adjustment for traditional cardiovascular risk factors, mean differences in baseline CCA-IMT per one-SD higher inflammatory marker were: 0.0082 mm for high-sensitivity C-reactive protein (p < 0.001); 0.0072 mm for fibrinogen (p < 0.001); and 0.0025 mm for leucocyte count (p = 0.033). 'Inflammatory load', defined as the number of elevated inflammatory markers (i.e. in upper two quintiles), showed a positive linear association with baseline CCA-IMT (p < 0.001). Longitudinal associations of baseline inflammatory markers and changes therein with CCA-IMT progression were null or at most weak. Participants with the highest 'inflammatory load' had a greater CCA-IMT progression (p = 0.015).

    Conclusion

    Inflammation was independently associated with CCA-IMT cross-sectionally. The lack of clear associations with CCA-IMT progression may be explained by imprecision in its assessment within a limited time period. Our findings for 'inflammatory load' suggest important combined effects of the three inflammatory markers on early atherosclerosis.
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    Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration.
    (PloS one, 2018-01) Lorenz, Matthias W; Gao, Lu; Ziegelbauer, Kathrin; Norata, Giuseppe Danilo; Empana, Jean Philippe; Schmidtmann, Irene; Lin, Hung-Ju; McLachlan, Stela; Bokemark, Lena; Ronkainen, Kimmo; Amato, Mauro; Schminke, Ulf; Srinivasan, Sathanur R; Lind, Lars; Okazaki, Shuhei; Stehouwer, Coen DA; Willeit, Peter; Polak, Joseph F; Steinmetz, Helmuth; Sander, Dirk; Poppert, Holger; Desvarieux, Moise; Ikram, M Arfan; Johnsen, Stein Harald; Staub, Daniel; Sirtori, Cesare R; Iglseder, Bernhard; Beloqui, Oscar; Engström, Gunnar; Friera, Alfonso; Rozza, Francesco; Xie, Wuxiang; Parraga, Grace; Grigore, Liliana; Plichart, Matthieu; Blankenberg, Stefan; Su, Ta-Chen; Schmidt, Caroline; Tuomainen, Tomi-Pekka; Veglia, Fabrizio; Völzke, Henry; Nijpels, Giel; Willeit, Johann; Sacco, Ralph L; Franco, Oscar H; Uthoff, Heiko; Hedblad, Bo; Suarez, Carmen; Izzo, Raffaele; Zhao, Dong; Wannarong, Thapat; Catapano, Alberico; Ducimetiere, Pierre; Espinola-Klein, Christine; Chien, Kuo-Liong; Price, Jackie F; Bergström, Göran; Kauhanen, Jussi; Tremoli, Elena; Dörr, Marcus; Berenson, Gerald; Kitagawa, Kazuo; Dekker, Jacqueline M; Kiechl, Stefan; Sitzer, Matthias; Bickel, Horst; Rundek, Tatjana; Hofman, Albert; Mathiesen, Ellisiv B; Castelnuovo, Samuela; Landecho, Manuel F; Rosvall, Maria; Gabriel, Rafael; de Luca, Nicola; Liu, Jing; Baldassarre, Damiano; Kavousi, Maryam; de Groot, Eric; Bots, Michiel L; Yanez, David N; Thompson, Simon G; PROG-IMT study group

    Aims

    Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk.

    Methods and results

    From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C.

    Conclusions

    We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.
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    Relationship of national institutes of health stroke scale to 30-day mortality in medicare beneficiaries with acute ischemic stroke.
    (J Am Heart Assoc, 2012-02) Fonarow, Gregg C; Saver, Jeffrey L; Smith, Eric E; Broderick, Joseph P; Kleindorfer, Dawn O; Sacco, Ralph L; Pan, Wenqin; Olson, Daiwai M; Hernandez, Adrian F; Peterson, Eric D; Schwamm, Lee H
    BACKGROUND: The National Institutes of Health Stroke Scale (NIHSS), a well-validated tool for assessing initial stroke severity, has previously been shown to be associated with mortality in acute ischemic stroke. However, the relationship, optimal categorization, and risk discrimination with the NIHSS for predicting 30-day mortality among Medicare beneficiaries with acute ischemic stroke has not been well studied. METHODS AND RESULTS: We analyzed data from 33102 fee-for-service Medicare beneficiaries treated at 404 Get With The Guidelines-Stroke hospitals between April 2003 and December 2006 with NIHSS documented. The 30-day mortality rate by NIHSS as a continuous variable and by risk-tree determined or prespecified categories were analyzed, with discrimination of risk quantified by the c-statistic. In this cohort, mean age was 79.0 years and 58% were female. The median NIHSS score was 5 (25th to 75th percentile 2 to 12). There were 4496 deaths in the first 30 days (13.6%). There was a strong graded relation between increasing NIHSS score and higher 30-day mortality. The 30-day mortality rates for acute ischemic stroke by NIHSS categories were as follows: 0 to 7, 4.2%; 8 to 13, 13.9%; 14 to 21, 31.6%; 22 to 42, 53.5%. A model with NIHSS alone provided excellent discrimination whether included as a continuous variable (c-statistic 0.82 [0.81 to 0.83]), 4 categories (c-statistic 0.80 [0.79 to 0.80]), or 3 categories (c-statistic 0.79 [0.78 to 0.79]). CONCLUSIONS: The NIHSS provides substantial prognostic information regarding 30-day mortality risk in Medicare beneficiaries with acute ischemic stroke. This index of stroke severity is a very strong discriminator of mortality risk, even in the absence of other clinical information, whether used as a continuous or categorical risk determinant. (J Am Heart Assoc. 2012;1:42-50.).