Twenty year predictors of peripheral arterial disease (PAD) compared with coronary heart disease (CHD) in the Scottish Heart Health Extended Cohort (SHHEC)

Hugh Tunstall-Pedoe (Lead / Corresponding author), Sanne A. E. Peters, Mark Woodward, Allan Struthers, Jill Belch

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Abstract

Background: Coronary heart disease and peripheral arterial disease (PAD) affect different vascular territories. Supplementing baseline findings with assays from stored serum, we compared their 20-year predictors.

Methods and Results: We randomly recruited 15 737 disease-free men and women aged 30 to 75 years across Scotland between 1984 and 1995 and followed them through 2009 for death and hospital diagnoses. Of these, 3098 developed coronary heart disease (19.7%), and 499 PAD (3.2%). Hazard ratios for 45 variables in the Cox model were adjusted for age and sex and for factors in the 2007 ASSIGN cardiovascular risk score. Forty-four of them were entered into parsimonious predictive models, tested by c-statistics and net reclassification improvements. Many hazard ratios diminished with adjustment and parsimonious modeling, leaving significant survivors. The hazard ratios were mostly higher in PAD. New parsimonious models increased the c-statistic and net reclassification improvements over ASSIGN variables alone but varied in their components and ranking. Coronary heart disease and PAD shared 7 of the 9 factors from ASSIGN: age, sex, family history, socioeconomic status, diabetes mellitus, tobacco smoking, and systolic blood pressure (but neither total nor high-density lipoprotein cholesterol); plus 4 new ones: NT-pro-BNP, cotinine, high-sensitivity C-reactive protein, and cystatin-C. The highest ranked hazard ratios for continuous factors in coronary heart disease were those for age, total cholesterol, high-sensitivity troponin, NT-pro-BNP, cotinine, apolipoprotein A, and waist circumference (plus 10 more); in PAD they were age, high-sensitivity C-reactive protein, systolic blood pressure, expired carbon monoxide, cotinine, socioeconomic status, and lipoprotein (a) (plus 5 more).

Conclusions: The mixture of shared with disparate determinants for arterial disease in the heart and the legs implies nonidentical pathogenesis: cholesterol dominant in the former, and inflammation (high-sensitivity C-reactive protein, diabetes mellitus, smoking) in the latter.
Original languageEnglish
Article numbere005967
Pages (from-to)1-19
Number of pages19
JournalJournal of the American Heart Association
Volume6
Issue number9
DOIs
Publication statusPublished - 18 Sep 2017

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Peripheral Arterial Disease
Coronary Disease
Cotinine
C-Reactive Protein
Health
Blood Pressure
Age Factors
Social Class
Diabetes Mellitus
Smoking
Cholesterol
Apolipoproteins A
Social Adjustment
Sex Factors
Cystatin C
Lipoprotein(a)
Troponin
Scotland
Waist Circumference
Carbon Monoxide

Keywords

  • cohort study
  • coronary heart disease
  • epidemiology
  • peripheral arterial disease
  • risk prediction

Cite this

@article{b91f2468c12d46659a0e00d0ec7ee5e1,
title = "Twenty year predictors of peripheral arterial disease (PAD) compared with coronary heart disease (CHD) in the Scottish Heart Health Extended Cohort (SHHEC)",
abstract = "Background: Coronary heart disease and peripheral arterial disease (PAD) affect different vascular territories. Supplementing baseline findings with assays from stored serum, we compared their 20-year predictors.Methods and Results: We randomly recruited 15 737 disease-free men and women aged 30 to 75 years across Scotland between 1984 and 1995 and followed them through 2009 for death and hospital diagnoses. Of these, 3098 developed coronary heart disease (19.7{\%}), and 499 PAD (3.2{\%}). Hazard ratios for 45 variables in the Cox model were adjusted for age and sex and for factors in the 2007 ASSIGN cardiovascular risk score. Forty-four of them were entered into parsimonious predictive models, tested by c-statistics and net reclassification improvements. Many hazard ratios diminished with adjustment and parsimonious modeling, leaving significant survivors. The hazard ratios were mostly higher in PAD. New parsimonious models increased the c-statistic and net reclassification improvements over ASSIGN variables alone but varied in their components and ranking. Coronary heart disease and PAD shared 7 of the 9 factors from ASSIGN: age, sex, family history, socioeconomic status, diabetes mellitus, tobacco smoking, and systolic blood pressure (but neither total nor high-density lipoprotein cholesterol); plus 4 new ones: NT-pro-BNP, cotinine, high-sensitivity C-reactive protein, and cystatin-C. The highest ranked hazard ratios for continuous factors in coronary heart disease were those for age, total cholesterol, high-sensitivity troponin, NT-pro-BNP, cotinine, apolipoprotein A, and waist circumference (plus 10 more); in PAD they were age, high-sensitivity C-reactive protein, systolic blood pressure, expired carbon monoxide, cotinine, socioeconomic status, and lipoprotein (a) (plus 5 more).Conclusions: The mixture of shared with disparate determinants for arterial disease in the heart and the legs implies nonidentical pathogenesis: cholesterol dominant in the former, and inflammation (high-sensitivity C-reactive protein, diabetes mellitus, smoking) in the latter.",
keywords = "cohort study, coronary heart disease, epidemiology, peripheral arterial disease, risk prediction",
author = "Hugh Tunstall-Pedoe and Peters, {Sanne A. E.} and Mark Woodward and Allan Struthers and Jill Belch",
note = "The Scottish Heart Health Extended Cohort (SHHEC) was funded by the Scottish Health Department Chief Scientist Organization, the British Heart Foundation, and the FP Fleming Trust. The MORGAM collaboration was funded by the European Commission Seventh Framework Programme, references FP7/2007-2013 (HEALTH-F4-2007-2014113, ENGAGE; HEALTH-F3-2010-242244, CHANCES). The MORGAM Biomarker Study (serum biomarkers in the MORGAM populations) was funded by the Medical Research Council, London (reference G0601463, No 80983). The BiomarCaRE Project (Biomarkers for Cardiovascular Risk Assessment in Europe) was funded by the European Commission Seventh Framework Programme FP7/2007-2013 (reference HEALTHF2-2011-278913).",
year = "2017",
month = "9",
day = "18",
doi = "10.1161/JAHA.117.005967",
language = "English",
volume = "6",
pages = "1--19",
journal = "Journal of the American Heart Association",
issn = "2047-9980",
publisher = "American Heart Association",
number = "9",

}

TY - JOUR

T1 - Twenty year predictors of peripheral arterial disease (PAD) compared with coronary heart disease (CHD) in the Scottish Heart Health Extended Cohort (SHHEC)

AU - Tunstall-Pedoe, Hugh

AU - Peters, Sanne A. E.

AU - Woodward, Mark

AU - Struthers, Allan

AU - Belch, Jill

N1 - The Scottish Heart Health Extended Cohort (SHHEC) was funded by the Scottish Health Department Chief Scientist Organization, the British Heart Foundation, and the FP Fleming Trust. The MORGAM collaboration was funded by the European Commission Seventh Framework Programme, references FP7/2007-2013 (HEALTH-F4-2007-2014113, ENGAGE; HEALTH-F3-2010-242244, CHANCES). The MORGAM Biomarker Study (serum biomarkers in the MORGAM populations) was funded by the Medical Research Council, London (reference G0601463, No 80983). The BiomarCaRE Project (Biomarkers for Cardiovascular Risk Assessment in Europe) was funded by the European Commission Seventh Framework Programme FP7/2007-2013 (reference HEALTHF2-2011-278913).

PY - 2017/9/18

Y1 - 2017/9/18

N2 - Background: Coronary heart disease and peripheral arterial disease (PAD) affect different vascular territories. Supplementing baseline findings with assays from stored serum, we compared their 20-year predictors.Methods and Results: We randomly recruited 15 737 disease-free men and women aged 30 to 75 years across Scotland between 1984 and 1995 and followed them through 2009 for death and hospital diagnoses. Of these, 3098 developed coronary heart disease (19.7%), and 499 PAD (3.2%). Hazard ratios for 45 variables in the Cox model were adjusted for age and sex and for factors in the 2007 ASSIGN cardiovascular risk score. Forty-four of them were entered into parsimonious predictive models, tested by c-statistics and net reclassification improvements. Many hazard ratios diminished with adjustment and parsimonious modeling, leaving significant survivors. The hazard ratios were mostly higher in PAD. New parsimonious models increased the c-statistic and net reclassification improvements over ASSIGN variables alone but varied in their components and ranking. Coronary heart disease and PAD shared 7 of the 9 factors from ASSIGN: age, sex, family history, socioeconomic status, diabetes mellitus, tobacco smoking, and systolic blood pressure (but neither total nor high-density lipoprotein cholesterol); plus 4 new ones: NT-pro-BNP, cotinine, high-sensitivity C-reactive protein, and cystatin-C. The highest ranked hazard ratios for continuous factors in coronary heart disease were those for age, total cholesterol, high-sensitivity troponin, NT-pro-BNP, cotinine, apolipoprotein A, and waist circumference (plus 10 more); in PAD they were age, high-sensitivity C-reactive protein, systolic blood pressure, expired carbon monoxide, cotinine, socioeconomic status, and lipoprotein (a) (plus 5 more).Conclusions: The mixture of shared with disparate determinants for arterial disease in the heart and the legs implies nonidentical pathogenesis: cholesterol dominant in the former, and inflammation (high-sensitivity C-reactive protein, diabetes mellitus, smoking) in the latter.

AB - Background: Coronary heart disease and peripheral arterial disease (PAD) affect different vascular territories. Supplementing baseline findings with assays from stored serum, we compared their 20-year predictors.Methods and Results: We randomly recruited 15 737 disease-free men and women aged 30 to 75 years across Scotland between 1984 and 1995 and followed them through 2009 for death and hospital diagnoses. Of these, 3098 developed coronary heart disease (19.7%), and 499 PAD (3.2%). Hazard ratios for 45 variables in the Cox model were adjusted for age and sex and for factors in the 2007 ASSIGN cardiovascular risk score. Forty-four of them were entered into parsimonious predictive models, tested by c-statistics and net reclassification improvements. Many hazard ratios diminished with adjustment and parsimonious modeling, leaving significant survivors. The hazard ratios were mostly higher in PAD. New parsimonious models increased the c-statistic and net reclassification improvements over ASSIGN variables alone but varied in their components and ranking. Coronary heart disease and PAD shared 7 of the 9 factors from ASSIGN: age, sex, family history, socioeconomic status, diabetes mellitus, tobacco smoking, and systolic blood pressure (but neither total nor high-density lipoprotein cholesterol); plus 4 new ones: NT-pro-BNP, cotinine, high-sensitivity C-reactive protein, and cystatin-C. The highest ranked hazard ratios for continuous factors in coronary heart disease were those for age, total cholesterol, high-sensitivity troponin, NT-pro-BNP, cotinine, apolipoprotein A, and waist circumference (plus 10 more); in PAD they were age, high-sensitivity C-reactive protein, systolic blood pressure, expired carbon monoxide, cotinine, socioeconomic status, and lipoprotein (a) (plus 5 more).Conclusions: The mixture of shared with disparate determinants for arterial disease in the heart and the legs implies nonidentical pathogenesis: cholesterol dominant in the former, and inflammation (high-sensitivity C-reactive protein, diabetes mellitus, smoking) in the latter.

KW - cohort study

KW - coronary heart disease

KW - epidemiology

KW - peripheral arterial disease

KW - risk prediction

U2 - 10.1161/JAHA.117.005967

DO - 10.1161/JAHA.117.005967

M3 - Article

VL - 6

SP - 1

EP - 19

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

SN - 2047-9980

IS - 9

M1 - e005967

ER -