Cardiovascular disease and osteoporosis: Balancing risk management

Figures & data

Figure 1 Prevalence of traditional risk factors for cardiovascular disease in Canadian society according to gender.

Source: Statistics Canada, National Population Health Survey, 1996/97 and the Heart and Stroke Foundation of Canada, The Changing Face of Heart Disease and Stroke in Canada 2000, October 1999 (Heart and Stroke Foundation of Canada 2000, Statistics Canada 1999b).

Note: High cholesterol was defined as a plasma cholesterol level above of 5.2 mmol ·L^-1; Diabetes was evaluated by self-report; Hypertension was defined as a blood pressure of ≥140/90 mmHg; Inactivity was defined as an usual daily leisure-time energy expenditure of <1.5 kcal ·kg^-1·day^-1; Smoking was defined as daily tobacco smoking; Obesity was defined as a body mass index of >27; Alcohol was defined as alcohol use in excess of 9 and 14 drinks per week for women and men, respectively.

Table 1 Relationship between vascular and bone health

Investigation	Design	Population	Primary outcome measures	Key results
(Browner et al 1991)	Prospective, 2.8y	9074 women, >65y	BMD (SPA); cause of death (ICD-9 codes)	Each SD decrease in BMD of proximal radius resulted in a 70% increase stroke mortality. Age-adjusted BMD revealed a weak association with CV mortality.
(Uyama et al 1997)	Observational	30 women, 67–85y	BMD (DXA); carotid plaque score (ulltrasound)	Linear correlation with BMD and plaque score. No association with L2-L4 BMD and plaque.
(Vogt et al 1997a)	Observational	1292 women, mean age 71y	Blood flow-ankle/arm index; posterior tibial and brachial systolic BP; BMD (SPA and DXA)	>1SD change above mean annual index change resulted in reduced BMD at hip 2 fold vs. smallest SD change. A decrease of 2 SD in ankle/arm index was associated with a 3.7% decrease in hip BMD.
(Vogt et al 1997b)	Observational	2051 women, >65y	Aortic calcification (lateral radiographs); BMD (DXA)	No significant association.
(Barengolts et al 1998)	Observational	11 controls, 20 osteopenic, 14 women with osteoporosis, mean age 65y	BMD (DXA), coronary calcium (QCT)	Osteoporosis group had a significantly higher calcium score vs controls.
(von der Recke et al 1999)	Longitudinal observational	309 women, mean age 50y	Bone mass/BMC (SPA of forearm and lateral radiography of spine)	50y group: Each SD decrease in bone mass resulted in a 43% increase in all cause mortality and 2-fold increase in CV death.
	Recruited 1977–88, assessed 1994	754 women, mean age 70y	Cause of death (ICD-9 codes)	70y group: Bone mass in lowest quartile was associated with a 2 fold increased risk of CV death vs highest quartile.
(Hak et al 2000)	Longitudinal observational for >9y	236 women, 45–64y	Aortic calcification (radiographs), MCoA and RCoA	Progression of aortic calcification was associated with decreased MCoA (6.1%) and RCoA (8.9%).
	Cross-sectional	720 women, mean age 63y		No progression was associated with decreased MCoA (3.9%) and RCoA (6.9%). Inverse, graded, association between extent of aortic calcification and MCoA/RCoA.
(Kado et al 2000)	Longitudinal observational, 5.7y	6046 women, mean age 76y	Rate of BMD loss; cause-specific mortality	Each SD increase in rate of bone loss resulted in 1.3-fold increase in the risk of CHD death, 1.2-fold increase in the risk of atherosclerotic death and 1.6-fold increase in the risk of death due to pulmonary causes.
(Kiel et al 2001)	Longitudinal observational, 25–30y	346 women, 190 men, 28–62y at start of study	Cortical bone mass (radiogrammetry); aortic calcification (radiographs)	Each percent decrease of MCoA was associated with 7.3% increase in aortic calcification index in women.
(Aoyagi et al 2001)	Observational of a prospective cohort	524 Japanese American women, 43–80y	BMD of distal/proximal radius and calcaneus (SPA); aortic calcification (lateral and AP radiographs)	No significant association between osteoporosis and aortic calcification.
(Yamaguchi et al 2002)	Observational	214 women, 47–86y	BMD, TC, LDL-C, HDL-C, TG	Inverse correlation with BMD and LDL-C. Positive correlation with BMD and HDL-C. Low TG levels associated with vertebral fracture.
(Tanko et al 2003)	Observational	963 women, 60–85 yr	Aortic calcification (graded on lateral lumbar radiographs), and BMD (at the distal radius, lumbar spine, proximal femur)	Age, years since menopause, BMI, level of education, smoking history, and physical activity were significant common risk factors for AC and hip BMD. Aortic calcification was an independent predictor of hip BMD. In a subgroup analysis, women with a history of intermittent claudication showed more severe aortic calcification, lower hip BMD, and a higher prevalence of CHD compared to age-matched controls.
(Kiechl et al 2004)	Prospective, longitudinal (10 yr) population-based survey	N = 915, approximately 50% males and females (Mean Age approximately 59 yr)	Serum OPG, incident CVD, carotid atherosclerosis	Prevalence and severity of carotid atherosclerosis increased progressively with higher levels of OPG (even after controlling for sex and age). OPG was a significant and independent risk factor for 10-year incident cardiovascular disease and vascular mortality.
(Schulz et al 2004)	Observational Cross-sectional and Longitudinal	Cross-sectional: 2348 postmenopausal women (50yrs and older) Longitudinal: 228 postmenopausal followed 9 months to 8 yr later	Aortic calcification, BMD, fracture	Cross-sectional: Age-independent association between the degree of aortic calcification and bone density. Aortic calcification was associated with a 4.8 and 2.9-fold increase in the risk for vertebral and hip fractures, respectively. Bilateral hip fractures more common in those with calcification than those without. Longitudinal: Graded relationship between bone loss and the progression of vascular calcification.
(Magnus and Broussard 2005)	Observational	5,050 women and men aged 50–79 yr	BMD, MI (self-report), BMI, glucose, cholesterol, HDL, medications (self-report)	Participants who reported prior MI had significantly higher odds of having low BMD (after adjusting for CVD and osteoporosis risk factors). MI was significantly associated with low BMD in men, but not women.
(Tanko et al 2005)	Multicenter, randomized, double-blinded, placebo controlled Followed for 4yrs	2576 women, mean age = 66.5 yr (assigned to placebo group)	Incidence of fatal or nonfatal CV events, BMD (femoral neck and lumbar spine), traditional risk factors for CVD (BMI, blood pressure, smoking habit, lipid profile, and history or presence of hypertension, diabetes, hyperlipidemia, cardiovascular disease, and/or related major interventions)	Osteoporotic women had a 3.9-fold increased risk for cardiovascular events than women with low bone mass. Risk of cardiovascular events increased incrementally with the number and increasing severity of baseline vertebral fractures. Composite cardiovascular risk was higher in women with osteoporosis and they were also more frequent users of cardiovascular medications. The incidence of an acute cardiovascular event during the follow up was higher in women with osteoporosis (evident for both coronary and stroke events). Increased risk for cardiovascular events associated with osteoporosis could not be explained by common risk factors alone.
(Bagger et al 2006)	Longitudinal observational, 7.5 yr	N = 2662 Postmenopausal women, mean age = 65 yr	Aortic calcification, BMD, vertebral fractures (X-ray), hip fractures (self-report)	Advanced aortic calcification at baseline was significantly related to lower BMD and accelerated bone loss at the proximal femur. The severity of aortic calcification was an independent predictor of hip fractures (OR = 2.3).
(Hermann-Arnhof et al 2006)	Observational	97 patients undergoing elective coronary artery bypass surgery	OPG, cardiac troponin I, electrocardiography, homocysteine, C-reactive protein	Positive correlation between OPG before surgery and the number of diseased vessels. Positive correlation between OPG before surgery and the number of bypasses. Strong correlation between OPG before surgery and homocysteine OPG level for four patients who experienced cardiac complications was elevated.
(Sinnott et al 2006)	Observational	313 women (57 yr) and 167 men (55 yr)	Coronary calcium burden, BMD, self-report CHD risk factors, medical history	The degree of coronary calcification was inversely associated with BMD in postmenopausal women. After controlling for age, this association was absent.
(Jorgensen et al 2006)	Prospective, longitudinal, 6 yr	2,733 women, aged 55-74 yr	Carotid Artery (echogenic) plaques, nonvertebral fractures	The age-adjusted relative risk of fracture was significantly higher in women with echogenic plagues (1.7 (95% confidence interval 1.0–2.7).
(Bagger et al 2007)	Observational	176 women, aged 60–85 yr	Genotyped for epsilon (varepsilon) allelic variants of the ApoE gene, and measures of serum lipids (total cholesterol, triglycerides, HDL-C, LDL-C, apoA1, ApoB, Lp(a)), hip and spine BMD, aorta calcification, radiographic vertebral fracture and self-reported wrist and hip fractures, and cardiovascular events	Presence of the ApoE varepsilon4 allele was associated with a worsened serum lipid profile, but had no association with spine/hip BMD or aortic calcification. After adjusting for age, the risk of hip fractures but not wrist or vertebral fractures was increased in subjects with advanced vascular disease.

Abbreviations: AP, anterior posterior; BMC, bone mineral content; BMD, bone mineral density; BP, blood pressure; CHD, coronary heart disease; CV, cardiovascular; DXA, dual energy x-ray absorptiometry; HDL-C, high-density lipoprotein-cholesterol; ICD-9, International Classification of Diseases (9th edition); L_2-4, 2nd through 4th lumbar vertebrae; HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein-cholesterol; MCoA, metacarpal cortical area; PM, postmenopausal; QCT, quantitative computed tomography; RCoA, relative cortical area; SD, standard deviation; SPA, single photon absorptiometry; TC, total cholesterol; TG, triglycerides; OR, odds ratio; IMT, intimal medial thickening; OPG, osteoprotegerin; BMI, body mass index; MI, myocardial infarction.

Figure 2 Life expectancy and health-adjusted life expectancy in representative nations.

Abbreviations: LEX, Life Expectancy; HALE, Health-Adjusted Life Expectancy; JPN, Japan; SWI, Switzerland; AUS, Australia; SWE, Sweden; FRA, France; CAN, Canada; ITA, Italy; SPN, Spain; NOR, Norway; NZL, New Zealand; UK, United Kingdom; USA, United States of America; SL, Sierra Leone.

The Health-Adjusted Life Expectancy (HALE) Takes into account the years of ill-health, weighted according to severity, and subtracted from the anticipated life expectancy to provide the equivalent years of healthy life.

Source: World Health Organization, World Health Report 2001. http://www3.who.int/whosis/hale/hale.cfm?path=whosis,hale&language=english (World Health Organization 2001).

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