. 2019 Dec 22;2019:9849465. doi: 10.1155/2019/9849465

Table 1.

Description of individual studies and their outcomes and findings.

Author year	Population	Numbers and type of exposure	Study design	Age in years	Male, % in combat group	Follow up	Outcomes	Key finding/covariate adjustment
Combat + traumatic injury
Hrubec and Ryder 1980 [9]	US military WWII (1944–45) veterans	3890 proximal amputees	Retrospective cohort	>80% <30 years old at time of injury	100%	>30 years	All-cause and disease specific mortality	↑ adjusted all-cause (RR : 1.36 : 1.25–1.48) CVD (RR : 1.58 : 1.40–1.79) and CHD related death (RR : 1.56 : 1.36–1.79) among proximal amputees vs. injured. ↑ risk of all-cause (1.29 : 1.18–1.41), CVD (1.44 : 1.26–1.64) and CHD (1.45 : 1.24–1.68) death among proximal vs distal amputees and vs general population.
		2917 distal amputees		>80% <30 years old at time of injury
		2917 distal amputees		3 groups age matched
		3890 injured		Ages at analysis not provided
		US population (age matched)		Ages at analysis not provided

Labouret et al. 1987 [35]	French veterans	106 with combat related amputation (49 AKA)	Cross-sectional	Compared by age decades from 40–89 years	100%	>15 years	Systolic and diastolic blood pressure	Higher unadjusted prevalence of systolic (not diastolic) HTN in the amputees vs controls (56% vs. 29%; p < 0.02) and significant for each age decade comparison.
	WWI (1914) n = 23	184 age matched controls without HTN
	WWII (1939) n = 67
	Other n = 16

Rose et al. 1987 [36]	US Vietnam War veterans	19 AKA	Cross-sectional	20–22 at injury and 35–36 years at analysis	100%	≥;15 years	Insulin response to glucose infusion	↑ unadjusted rate of HTN (10/19) in amputees vs controls (1/12; p < 0.05); no difference lipid levels.
Rose et al. 1987 [36]	US Vietnam War veterans	12 age matched controls	Cross-sectional	20–22 at injury and 35–36 years at analysis	100%	≥;15 years	Insulin response to glucose infusion

Vollmar et al. 1989 [34]	German WWII (1939–1945) veterans	329 veterans with AKA	Cross-sectional	67.2 years AKA	100%	43.8 years from injury	Ultrasound diagnosis of infrarenal abdominal aortic aneurysms	↑ AKA in amputees vs controls (5.8% vs. 1.1%); no differences in risk of HTN, hyperlipidemia and DM (comparative data not reported)
		702 nonamputee veterans		67.2 years AKA
		702 nonamputee veterans		68.1 years controls with comparable burden of CVD risk factors

Yekutiel et al. 1989 [26]	Israeli War Veterans wars (1948–9, 1956, 1967, 1973)	53 traumatic lower limb amputees	Cross-sectional	57.2 years	100%	>20 years from injury	Hypertension, CHD and DM	↑ unadjusted prevalence of CHD in amputees vs controls (32.1% vs. 18.2%; p < 0.01) and DM (22.6% vs. 9.4%); no difference in HTN (35.8% vs. 35.2%)
Yekutiel et al. 1989 [26]	Israeli War Veterans wars (1948–9, 1956, 1967, 1973)	159 age and sex-matched controls	Cross-sectional	57.2 years	100%	>20 years from injury	Hypertension, CHD and DM

Lorenz et al. 1994 [25]	German population conflicts not stated	226 veterans with traumatic lower limb amputations	Cross-sectional	Age not reported (short report)	Not reported	Unreported but >1 year	Ultrasound diagnosis of abdominal aortic aneurysms	No difference in prevalence of aortic aneurysms among amputees (4.4%) vs controls (4%). No difference in risk of hypertension, diabetes or hyperlipidemia.
Lorenz et al. 1994 [25]	German population conflicts not stated	199 controls	Cross-sectional	Age not reported (short report)	Not reported	Unreported but >1 year	Ultrasound diagnosis of abdominal aortic aneurysms

Peles et al. 1995 [43]	Israel defence force veterans 1948–1974	52 Amputees	Cross-sectional	Amputees 52 years controls 53 years	100%	33 years after injury	Insulin resistance and autonomic function	Age adjusted ↑ in insulin levels among amputees vs controls; No unadjusted difference in glucose, lipids and blood pressure
Peles et al. 1995 [43]	Israel defence force veterans 1948–1974	53 nonmilitary controls	Cross-sectional	Amputees 52 years controls 53 years	100%	33 years after injury	Insulin resistance and autonomic function

Modan et al. 1998 [19]	Israeli army wounded 1948–1974	Cohort 1 201 veterans + traumatic lower limb amputation 1832 general US population	Retrospective cohort study	50% <40 years	100%	24-year	All-cause CVD and non CVD mortality	Two fold ↑ (amputees vs. controls) in unadjusted risk of all-cause (21.9% vs. 12.1% p < 0.001 among older) and CVD-related death (8.9% vs. 3.8%,p < 0.001).
		Cohort 2 101 amputees 96 controls (matched by age and ethnicity)	Cross-sectional				All-cause CVD and non CVD mortality
			Cross-sectional				CV risk factors	Cohort 2 ↑ plasma insulin levels (2 hour post oral glucose load) in amputees; No differences in unadjusted CHD (19.8% vs. 16.7%), cerebrovascular disease (3.0% vs. 5.2%), obesity, DM, HTN (43.6% vs. 35.4%), hyperlipidemia (37.6% vs. 30.2%)

Shahriar et al. 2009 [37]	Iranian wars	327 bilateral lower limb amputees	Cross-sectional	42 years at analysis with age of 20.6 years at injury control group age not reported	100%	Mean 22.3	Obesity and CVD risk factors	↑ unadjusted risk of HTN (28.5% vs. 20.4%: p < 0.05), total and LDL cholesterol (P < 0.05) obesity (31.8% vs. 22.3%) and smoking (31.8% vs. 22.3%; p < 0.05) versus control
Shahriar et al. 2009 [37]	Iranian wars	Iranian general population (demographics undefined) [5]	Cross-sectional		100%	Mean 22.3	Obesity and CVD risk factors

Kunnas et al. 2011 [24]	Finnish Military WWII veterans	102 injured combat veterans	Prospective cohort study	55 years	100%	28 years	CHD mortality	(↑ adjusted risk of CHD (HR 1.7 : 1.1–2.5; p = 0.02) death among injured/wounded vs control. No difference in total cholesterol or DM.
Kunnas et al. 2011 [24]	Finnish Military WWII veterans	565 non injured veterans	Prospective cohort study	55 years	100%	28 years	CHD mortality

Stewart et al. 2015 [27]	US Military Iraq and Afghanistan wars 2002–2011	3846 severe traumatic injuries	Retrospective cohort	25–29.2 years	≥98%	1.1–4.3 years	Armed Forces Medical Examiner System (AFMES) database of outcomes	Each 5-point ↑in the ISS linked to a 6%, 13% and 13% ↑ in the adjusted risk of HTN (OR 1.06; 1.02–1.09; P = 0.003), CAD (1.13; 95% CI 1.03–1.25; P = 0.01), DM (1.13; 1.04–1.23; P = 0.003). ↑ Risk versus control population
Stewart et al. 2015 [27]	US Military Iraq and Afghanistan wars 2002–2011	Millennium cohort [30, 41]	Retrospective cohort	25–29.2 years	≥98%	1.1–4.3 years

Ejtahed et al.2017 [46]	Iran veterans of Iran-Iraq War	235 veterans with bilateral traumatic lower limb amputations vs general population	Cross-sectional	31.5 years at injury and 52 years at follow up	100%	32.1 years form injury	Metabolic syndrome	2-fold ↑ in metabolic syndrome, including HTN, insulin levels, hyperlipidemia and obesity (amputees (62.1%) vs general Iranian population (27.5% )
Ejtahed et al.2017 [46]	Iran veterans of Iran-Iraq War		Cross-sectional	Age for comparator not reported	100%	32.1 years form injury	Metabolic syndrome

Uninjured combat ^‡
Bullman et al. 1990 [20]	US Vietnam War veterans	6668 high-combat veterans deaths	Retrospective cohort	Similar ages in both groups	100%	Median follow up >5 years	ICD8 8 codes	↓ in proportionate CVD mortality vs control group (mortality ratio 0.93 : 0.88–0.98).
Bullman et al. 1990 [20]	US Vietnam War veterans	27917 low combat veteran deaths	Retrospective cohort	Similar ages in both groups	100%	Median follow up >5 years	ICD8 8 codes

O'Toole et al. 1996 [40]	Australian Vietnam War veterans	641 army veterans (10.8% injured) vs age-sex matched population expected	Cross-sectional	29.5 years at military discharge	100%	>15 years	Self-reported physical health status	↑ adjusted risk of HTN (RR 2.17 : 1.71–2.62), DM (2.71 : 1.32–4.09) and lipids (2.73 : 1.94–3.52); CVD (RR 1.98 : 0.52–2.33) not significant. No relationship between increasing combat burden to any CVD outcomes or risk factors.

MacFarlane et al. 2000 [21]	UK Military veterans of Gulf War I (1990–91)	53416 war veterans	Retrospective cohort	71.5% <30 years at study enrolment	97.7%	8 years	Multiple	No significant difference in all-cause (MRR 1.05 : 0.91–1.21) and CVD mortality (0.74 : 0.49–1.12) among deployed vs nondeployed veterans mortality.
MacFarlane et al. 2000 [21]	UK Military veterans of Gulf War I (1990–91)	53450 nondeployed military	Retrospective cohort	71.5% <30 years at study enrolment	97.7%	8 years	Multiple

Eisen et al. 2005 [42]	US Military Gulf War (1991)	1061deployed war veterans	Cross-sectional	30.9 years deployed	78% in both groups	10 years	Physical health and QOL	No significant difference in adjusted risk of DM (1.52 : 0.81–2.85) or hypertension (0.90 : 0.60–1.33).
Eisen et al. 2005 [42]	US Military Gulf War (1991)	1128 nondeployed	Cross-sectional	32.6 years non deployed^∗	78% in both groups	10 years	Physical health and QOL

Granado et al. 2009 [41]	US Military (2001–2003) (25% Iraq and Afghanistan)	4385 combat	Prospective cohort	Not reported	74.8–86%	2.7 years	SF-36 questionnaire arterial hypertension	↑ adjusted incidence of HTN among multiple combat veterans vs. nondeployers (OR 1.33 : 1.07–1.65:p < 0.05).
		4444 deployed noncombat		But grouped by birth^∗ decades
		27232 nondeployed		But grouped by birth^∗ decades

Kang et al. 2009 [28]	US Gulf War (1991) veterans	6111 war veterans	Cross-sectional analysis of prospective cohort	31.5 years for war veterans	79.9% active 78.2% control	14 years	Health questionnaires	↑ adjusted self-reported prevalence of HTN (RR 1.11 : 1.04–1.19), stroke (RR 1.32 : 1.14–1.52), CHD (RR 1.22 : 1.08–1.39) and obesity. No significant difference in DM (RR 1.11 : 0.99–1.25).
		3859 veterans not deployed to Persian Gulf		31.5 years for war veterans
		3859 veterans not deployed to Persian Gulf		33.6 years for control (in 1991) ^∗

Johnson et al. 2010 [33]	US Veterans World War II 40.6% (1941–1945), Korean War 34.6% (1950–1953) Vietnam Conflict 16.8% (1961–1975)	1178 combat (13.1% veterans) 2127 noncombat (deployed) veterans	Prospective cohort	19–20 years at enrolment	100%	36 years after military entry	Carotid intima-media thickness (CIMT) and carotid plaque	↑ age-adjusted CIMT in combat veterans (Risk difference 12.79 µm : 0.72–24.86) noncombat veterans. No significant difference in carotid plaque noted.
				57.3 years combat veterans
		2,042 nonmilitary		57.3 years combat veterans
				51.8 years non veterans
				54.1 years non-combat veterans^∗

Johnson et al. 2010 [44]	US Veterans World War II 40.6% (1941–1945), Korean War 34.6% (1950–1953) Vietnam Conflict 16.8% (1961–1975)	1178 combat veterans (13.1% injured)	Prospective cohort	19–20 years at enrolment	100%	36 years after military entry	Myocardial infarction unstable angina or CHD-related death	No significant differences in adjusted CHD between combat (13.2%) and noncombat veterans (11.3%), and nonveterans (11.6%); similar ischaemic stroke risk (7.76% vs. 5.22% vs. 6.43%). ↑ prevalence of DM combat vs noncombat but no significant difference in HTN, lipid profiles.
		1178 combat veterans (13.1% injured)		57.3 combat veterans
		2127 noncombat (deployed) veterans		57.3 combat veterans
		2127 noncombat (deployed) veterans		51.8 non veterans
		2,042 nonmilitary		54.1 non-combat veterans^∗

Crum-Cianflone et al. 2014 [30]	US Military Iraq and Afghanistan wars 2001–2009	12280 deployed combat	Prospective cohort	34.4 years at baseline and mean age at CHD diagnosis 43.1 years (comparative ages not reported)	84.4%	5.6 years	Coronary heart disease	Combatants ↑ adjusted (age, sex, race) risk of CHD (OR 1.63 : 1.11–2.40) vs deployed noncombat servicemen but ↓ unadjusted risk of DM and hypertension.
		10602 deployed noncombat
		37143 nondeployed military

Schlenger et al. 2015 [22]	US Vietnam War veterans	1632 theatre veterans	Retrospective cohort	41.5 years theatre veterans	>95%	>10 years	ICD codes for causes of death	No significant difference in all cause (16.79% vs. 16.61%), CVD (5.23% vs. 3.81%) or CHD-related (3.02% vs. 2.33%) deaths.
Schlenger et al. 2015 [22]	US Vietnam War veterans	716 Era (noncombat) veteran controls	Retrospective cohort	40.9 years control	>95%	>10 years	ICD codes for causes of death

Barth et al. 2016 [23]	UK Gulf War (1991)	621901 Gulf War veterans 746247 noncombat veterans	Retrospective Cohort	28 years – war veterans	93% active	13.6 years	All cause and disease specific mortality (ICD-9)	No difference in adjusted CVD mortality among Gulf War vs noncombat veterans (0.99 : 0.093–1.05) but ↓ all-cause mortality (RR 0.97 : 0.95%–0.99%). ↓ risk of all cause (RR 0.49 : 0.48–0.50) and CVD (RR 0.43 : 0.42–0.45) related mortality in Gulf War veterans vs. US population.
		621901 Gulf War veterans 746247 noncombat veterans		30 years – noncombat veterans^∗	86.7% control^∗
		US general population		30 years – noncombat veterans^∗	Significant

Sheffler et al. 2016 [32]	US Vietnam War veterans 1959–1973	107 combat veterans	Cross-sectional	45.4 years – combat	100%	10 years	Multiple health outcomes	↓ adjusted (OR 0.25 : 0.09–0.63; p = 0.003) rate of diabetes among noncombat servicemen. No difference in unadjusted CHD, hypertension, heart attacks or stroke.
Sheffler et al. 2016 [32]	US Vietnam War veterans 1959–1973	620 noncombat controls	Cross-sectional	46.0 years – noncombat	100%	10 years	Multiple health outcomes

Thomas et al. 2017 [31]	US Military veterans Vietnam war (43.6%)	564 combat veterans (29.2% injured)	Cross-sectional	59.0 years – combat	87.6–93%	>20 years	Validated health questionnaires	↑ adjusted risk of stroke (OR 1.38 : 1.03–3.33); no difference in adjusted risk of heart attacks, high cholesterol HTN and other heart disease.
		564 combat veterans (29.2% injured)		61.3 years – noncombat^∗
		916 noncombat veterans		61.3 years – noncombat^∗

Hinojosa 2018 [29]	US Military Iraq and Afghanistan Wars 2012–2015	14932 combat veterans	Cross-sectional	56.1 years – veterans 48.8 years – control^∗	66.3% in military group vs 42% in nonmilitary controls^∗	>1 year	CVD outcomes	↑ adjusted prevalence of HTN in veterans (OR 1.49 : 1.23–1.81), CHD (OR 1.55 : 1.0–2.40), and heart attacks (2.26 : 1.41–3.62); ↑ rates of stroke among male only veterans (OR 3.32 : 2.03–5.47).
Hinojosa 2018 [29]	US Military Iraq and Afghanistan Wars 2012–2015	135135 civilians	Cross-sectional	56.1 years – veterans 48.8 years – control^∗	66.3% in military group vs 42% in nonmilitary controls^∗	>1 year	CVD outcomes

CHD, coronary heart disease; DM, diabetes mellitus; CVD, cardiovascular disease; HTN, hypertension, Results presented in brackets as odds ratio, relative risk and 95% confidence intervals unless stated; CHD, coronary heart disease; DM, diabetes mellitus; CVD cardiovascular disease; HTN, hypertension; AKA, above knee amputation; ISS, injury severity Score. Results presented in brackets as odds ratio (OR), relative risk (RR), mortality rate ratio (MRR), hazard ratio (HR) and 95% confidence intervals unless stated; ^‡refers to studies where proportion with traumatic injury <50%. ^∗Detailed demographics for this population either not fully defined or disclosed.