Blood Lead Levels and Risk of Atherosclerosis in the Carotid Artery: Results from a Swedish Cohort

Background: Lead exposure has been associated with increased incidence of adverse clinical cardiovascular outcomes. Atherosclerosis has been suggested as one of the underlying mechanisms, and findings from experimental studies support this, but human data are scarce. Objectives: Our objective was to determine the association between environmental lead exposure based on blood lead (B-Pb) concentrations and the prevalence of atherosclerotic plaque in the carotid artery. Methods: We used cross-sectional data from the Malmö Diet and Cancer Study cardiovascular cohort (MDCS-CC; recruitment in 1991–1994) covering 4,172 middle-aged men and women. B-Pb at baseline, measured by inductively coupled plasma mass spectrometry, was used as the exposure biomarker. The presence of atherosclerotic plaque in the carotid artery was determined by B-mode ultrasonography. We used logistic regression to estimate odds ratios (ORs) for prevalence of plaque in the carotid artery according to B-Pb quartiles. Results: The median B-Pb was 25μg/L (range: 1.5–258), and 36% of the cohort had any atherosclerotic plaque. After controlling for confounders and known cardiovascular risk factors, the OR for prevalence of plaque in the highest quartile (Q4) of B-Pb compared with the lowest quartile (Q1) was 1.35 (95% CI: 1.09, 1.66) in the total group, 1.58 (95% CI: 1.20, 2.08) among women, and 1.18 (95% CI: 0.83, 1.69) among men. Among women, associations were limited to those who were postmenopausal [OR for Q4 vs. Q1=1.72 (95% CI: 1.26, 2.34) vs. OR=0.96 (95% CI: 0.49, 1.89 in premenopausal women)]. Associations were weak and nonsignificant in never-smokers [OR for Q4 vs. Q1=1.14 (95% CI: 0.81, 1.61)]. Discussion: Our study shows an association between B-Pb concentrations and occurrence of atherosclerotic plaque in the carotid artery, adding evidence for an underlying pro-atherogenic role of lead in cardiovascular disease. Associations appeared to be limited to postmenopausal (vs. premenopausal) women. https://doi.org/10.1289/EHP5057

[1]  O. Melander,et al.  Blood Lead Levels and Decreased Kidney Function in a Population-Based Cohort. , 2018, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[2]  O. Franco,et al.  Environmental toxic metal contaminants and risk of cardiovascular disease: systematic review and meta-analysis , 2018, British Medical Journal.

[3]  R. Hornung,et al.  Low-level lead exposure and mortality in US adults: a population-based cohort study. , 2018, The Lancet. Public health.

[4]  C. Crainiceanu,et al.  Declining exposures to lead and cadmium contribute to explaining the reduction of cardiovascular mortality in the US population, 1988-2004. , 2017, International journal of epidemiology.

[5]  F. Hu,et al.  Plasma Metal Concentrations and Incident Coronary Heart Disease in Chinese Adults: The Dongfeng-Tongji Cohort , 2017, Environmental health perspectives.

[6]  Mohammad Hossein Khosravi,et al.  Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016 , 2017, Lancet.

[7]  B. Fagerberg,et al.  Low-level exposure to lead, blood pressure, and hypertension in a population-based cohort. , 2016, Environmental research.

[8]  M. Buser,et al.  Urinary and blood cadmium and lead and kidney function: NHANES 2007-2012. , 2016, International journal of hygiene and environmental health.

[9]  O. Melander,et al.  Risk factors for the progression of carotid intima-media thickness over a 16-year follow-up period: the Malmö Diet and Cancer Study. , 2015, Atherosclerosis.

[10]  G. Bergström,et al.  Is Cadmium Exposure Associated with the Burden, Vulnerability and Rupture of Human Atherosclerotic Plaques? , 2015, PloS one.

[11]  G. Lamas,et al.  Metal pollutants and cardiovascular disease: mechanisms and consequences of exposure. , 2014, American heart journal.

[12]  K. Moreau,et al.  Vascular Aging across the Menopause Transition in Healthy Women , 2014, Advances in vascular medicine.

[13]  J. Sommar,et al.  End-stage renal disease and low level exposure to lead, cadmium and mercury; a population-based, prospective nested case-referent study in Sweden , 2013, Environmental Health.

[14]  L. Lind,et al.  Circulating levels of metals are related to carotid atherosclerosis in elderly. , 2012, The Science of the total environment.

[15]  E. Guallar,et al.  Associations of blood lead with estimated glomerular filtration rate using MDRD, CKD-EPI and serum cystatin C-based equations. , 2011, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[16]  S. Kiechl,et al.  Lead Contributes to Arterial Intimal Hyperplasia Through Nuclear Factor Erythroid 2–Related Factor–Mediated Endothelial Interleukin 8 Synthesis and Subsequent Invasion of Smooth Muscle Cells , 2010, Arteriosclerosis, thrombosis, and vascular biology.

[17]  G. Berglund,et al.  Ability of physical activity measurements to assess health-related risks , 2009, European Journal of Clinical Nutrition.

[18]  N. Vaziri,et al.  Mechanisms of lead-induced hypertension and cardiovascular disease. , 2008, American journal of physiology. Heart and circulatory physiology.

[19]  J. Schwartz,et al.  Cumulative Community-Level Lead Exposure and Pulse Pressure: The Normative Aging Study , 2007, Environmental health perspectives.

[20]  P. Vokonas,et al.  Lead Levels and Ischemic Heart Disease in a Prospective Study of Middle-Aged and Elderly Men: the VA Normative Aging Study , 2007, Environmental health perspectives.

[21]  E. Guallar,et al.  Lead Exposure and Cardiovascular Disease—A Systematic Review , 2006, Environmental health perspectives.

[22]  Ellen K. Silbergeld,et al.  Blood Lead Below 0.48 &mgr;mol/L (10 &mgr;g/dL) and Mortality Among US Adults , 2006 .

[23]  Lisa B. Mirel,et al.  Blood Lead Levels and Death from All Causes, Cardiovascular Disease, and Cancer: Results from the NHANES III Mortality Study , 2006, Environmental health perspectives.

[24]  A. Sharrett,et al.  Confounding of the relation between homocysteine and peripheral arterial disease by lead, cadmium, and renal function. , 2006, American journal of epidemiology.

[25]  P. Muntner,et al.  Continued decline in blood lead levels among adults in the United States: the National Health and Nutrition Examination Surveys. , 2005, Archives of internal medicine.

[26]  A. Al-Nasser,et al.  Is lead considered as a risk factor for high blood pressure during menopause period among Saudi women? , 2005, International journal of hygiene and environmental health.

[27]  J. Tanus-Santos,et al.  A Critical Review of Biomarkers Used for Monitoring Human Exposure to Lead: Advantages, Limitations, and Future Needs , 2005, Environmental health perspectives.

[28]  S. Skerfving,et al.  Tubular and Glomerular Kidney Effects in Swedish Women with Low Environmental Cadmium Exposure , 2005, Environmental health perspectives.

[29]  A. Sharrett,et al.  Metals in Urine and Peripheral Arterial Disease , 2004, Environmental health perspectives.

[30]  Robert M Califf,et al.  Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. , 2004, The New England journal of medicine.

[31]  Charles E McCulloch,et al.  Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. , 2004, The New England journal of medicine.

[32]  Elizabeth Selvin,et al.  Lead, Cadmium, Smoking, and Increased Risk of Peripheral Arterial Disease , 2004, Circulation.

[33]  Ja‐Liang Lin,et al.  Environmental exposure to lead and progression of chronic renal diseases: a four-year prospective longitudinal study. , 2004, Journal of the American Society of Nephrology : JASN.

[34]  Ellen K Silbergeld,et al.  Blood lead, blood pressure, and hypertension in perimenopausal and postmenopausal women. , 2003, JAMA.

[35]  A. Bernard,et al.  Biomarkers of Renal Effects in Children and Adults with Low Environmental Exposure to Heavy Metals , 2003, Journal of toxicology and environmental health. Part A.

[36]  Ellen Silbergeld,et al.  Blood lead levels and mortality. , 2002, Archives of internal medicine.

[37]  W. Robertson.  Blood lead levels. , 2002, Pediatrics.

[38]  P. Touboul,et al.  Carotid plaques, but not common carotid intima–media thickness, are independently associated with aortic stiffness , 2002, Journal of hypertension.

[39]  G. Berglund,et al.  The Malmö diet and cancer study: representativity, cancer incidence and mortality in participants and non‐participants , 2001, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[40]  G. Berglund,et al.  Occupational status, educational level, and the prevalence of carotid atherosclerosis in a general population sample of middle-aged Swedish men and women: results from the Malmö Diet and Cancer Study. , 2000, American journal of epidemiology.

[41]  L. Sanín,et al.  The influence of bone and blood lead on plasma lead levels in environmentally exposed adults. , 1998, Environmental health perspectives.

[42]  I. Hertz-Picciotto,et al.  Blood lead levels in relation to menopause, smoking, and pregnancy history. , 1995, American journal of epidemiology.

[43]  T. Kaji,et al.  Stimulatory effect of lead on the proliferation of cultured vascular smooth-muscle cells. , 1995, Toxicology.

[44]  G. Berglund,et al.  Design and feasibility , 1993 .

[45]  T. Kristensen,et al.  Blood lead as a cardiovascular risk factor. , 1992, American journal of epidemiology.

[46]  G. Berglund,et al.  Noninvasive quantification of atherosclerotic lesions. Reproducibility of ultrasonographic measurement of arterial wall thickness and plaque size. , 1992, Arteriosclerosis and thrombosis : a journal of vascular biology.

[47]  E. Silbergeld,et al.  Lead and osteoporosis: mobilization of lead from bone in postmenopausal women. , 1988, Environmental research.

[48]  S. Pocock,et al.  The relationship between blood lead, blood pressure, stroke, and heart attacks in middle-aged British men. , 1988, Environmental health perspectives.

[49]  M. Svartengren,et al.  Decreased blood lead levels in residents of Stockholm for the period 1980-1984. , 1986, Scandinavian journal of work, environment & health.

[50]  P. Barry.  A comparison of concentrations of lead in human tissues. , 1975, British journal of industrial medicine.

[51]  Ashutosh Kumar Singh,et al.  Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015 , 2016, Lancet.

[52]  B. Fagerberg,et al.  Cadmium exposure and atherosclerotic carotid plaques--results from the Malmö diet and Cancer study. , 2015, Environmental research.

[53]  I. Bergdahl,et al.  Chapter 43 – Lead , 2015 .

[54]  E. Guallar,et al.  Blood Lead Below 0.48 (cid:1) mol/L (10 (cid:1) g/dL) and Mortality Among US Adults , 2006 .

[55]  F. McNeill,et al.  Lead in bone: storage site, exposure source, and target organ. , 1993, Neurotoxicology.

[56]  G. Johnson,et al.  Lead exposure. , 1992, The Western journal of medicine.