Original Research Article – Supplementary materials
High blood pressure and associated risk factors as indicator of pre-clinical hypertension in rural West Africa: A focus on children and adolescents in The Gambia
Modou Jobe
a*, Schadrac C. Agbla
b*, Andrew M. Prentice
a,c, Branwen J. Hennig
a,c§a
Nutrition Theme, MRC Unit The Gambia, Atlantic Boulevard, Fajara, P. O. Box 273, Banjul, The Gambia.
b
Tropical Epidemiology Group, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
c
MRC International Nutrition Group, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
*
These authors contributed equally
1. Supplementary materials and methods
1.1. Sibship size in Gambian study population
Supplementary Table 1 Details of sibship size in our rural Gambian population where shared maternal ID was used to determine relatedness.
(submitted as separate file)
1.2. Definition of anemia
Supplementary Table 2 Definition of anemia according to age- and sex-specific cut-offs of hemoglobin level
2.
(submitted as separate file)
1.3. Statistical analyses
We estimated age-sex specific height z-scores using GAMLSS with Box-Cox t-distribution where the mean, coefficient of variation, skewness and kurtosis were modelled as non-parametric smoothing cubic spline functions of age. Optimum smoothing degrees of freedom for each parameter were selected such that the generalized Akaike information criterion (AIC) was minimized with a penalty of 2.5.
Next, we computed the 95th percentiles for SBP and DBP by sex for children aged 5 to <18y using GAMLSS with Box-Cox Cole and Green (BCCG) distribution and the mean values of SBP and DBP as function of a smoothing cubic spline of age and height z-scores. These 95th percentiles were used to define high-BP in 5 to <18y
3. Reference values of 50th, 90th, and 95th percentiles for SBP and DBP by age and height (at the 5th, 10th, 25th, 50th, 75th, 90th and 95th percentiles) for boys and girls respectively are shown in Supplementary Table 3. Age- and sex-specific height percentiles for girls and boys aged 5 to 17y are also shown in Supplementary Table 4.
Let Y > 0 be a positive random variable following a BCCG(μ, σ, ν). The transformed random variable
Z is given by
4:
𝑍 = 1 σν
𝑌 µ
!
− 1 , 𝑖𝑓 ν ≠ 0 1
σ 𝑙𝑜𝑔 𝑌
µ , 𝑖𝑓 ν = 0
and where the random variable Z is assumed to follow a truncated standard normal distribution.
The percentiles are derived such as
5,6:
𝑌
!= µ 1 + σνz
!,! !/!, 𝑖𝑓 ν ≠ 0 µexp (σνz
!,!), 𝑖𝑓 ν = 0 where z
!,!is the 100α centile of a truncated standard normal distribution.
2. Supplementary results
Supplementary Table 3 Blood pressure (BP) levels for (A) boys and (B) girls 5 to <18 years by age and height percentile and (C) those aged ≥18 years, in rural Gambia
(submitted as separate file)
Supplementary Table 4 Age- and sex-specific height percentiles for girls and boys aged 5 to
<18y in rural Gambia (submitted as separate file)
Supplementary Table 5 Blood pressure (BP) cut-offs for high-BP definition for (A) boys and (B) girls 5 to <18 years by age and height percentile in rural Gambians alongside cut-offs from the US 4
thReport
3(submitted as separate file)
Supplementary Table 6 Association between age and education status in ≥18y rural Gambians
(submitted as separate file)
Supplementary Figure 1 Blood pressure cut-offs for high-BP by age and height percentiles in (A) boys and (B) girls aged 5 to <18y in rural Gambians and compared to hypertension cut-offs from the US 4
thReport
3(submitted as separate file)
References
1. Standards of medical care in diabetes - 2007. Diabetes Care. 2007;30(Supplement 1):S4–41.
2. WHO. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity [Internet]. Vitam. Miner. Nutr. Inf. Syst. 2011 [cited 2015 Nov 10]. Available from:
http://www.who.int/vmnis/indicators/haemoglobin.pdf
3. Roccella E. The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Pediatrics. 2004;114(2):555–574.
4. Stasinopoulos DM, Rigby RA. Generalized Additive Models for Location Scale and Shape (GAMLSS) in R. J Stat Softw. 2007;23(7).
5. Rigby RA, Stasinopoulos DM. Smooth centile curves for skew and kurtotic data modelled using the Box-Cox power exponential distribution. Stat Med. 2004 Oct 15;23(19):3053–76.
6. Indrayan A. Demystifying LMS and BCPE methods of centile estimation for growth and other
health parameters. Indian Pediatr. 2014;51(1):37–43.
Supplementary Figure 1 Blood pressure cut-offs for high-BP by age and height percentiles in (A) boys and (B) girls aged 5 to <18y in rural Gambians and compared to hypertension cut-offs from the US 4
thReport
3(A) Systolic blood pressure (SBP) and diastolic blood pressure (DBP) in males
(B) Systolic blood pressure (SBP) and diastolic blood pressure (DBP) in females
Note: Our high-BP and the hypertension categories as stipulated by the 4th Report are not directly comparable; we show these alongside each other for information purposes only. N=3637. For further details regarding the calculation of age- and sex-specific height and BP percentiles please see statistical methods in main paper and above. Blue square represents the BP cut-offs presented in 4th Report 3, while the red triangle represents the BP cut-offs for our rural Gambians population. Note: Our population covered the whole spectrum of age, sex and heights and we estimated from these data the reference values of 50th, 90th, 95th and 99th percentiles for SBP and DBP by age and height (at the 5th, 10th, 25th, 50th, 75th, 90th and 95th percentiles) in boys and girls as shown in Supplementary Tables 3 and 4.
Supplementary Table 1 Details of sibship size in our rural Gambian population where shared maternal ID was used to determine relatedness.
Sibship size Sibship group in <18y n (%)
Sibship group in 18y and above n (%)
Singleton 586 (28.7) 664 (30.0)
2 422 (20.7) 188 (8.5)
3 275 (13.5) 41 (1.9)
4 137 (6.7) 9 (0.4)
5 42 (2.1) 3 (0.1)
6 7 (0.3) 0 (0.0)
7 2 (0.1) 0 (0.0)
Maternal ID not available
a568 (27.9) 1309 (59.1)
Total number of sibships 2039 (100) 2214 (100)
Total number of study participants <18y was 3637 and those aged 18y and above was 2523. a Where maternal ID was not available, individuals were treated as singletons.
Supplementary Table 2 Definition of anemia according to age- and sex-specific cut-offs of hemoglobin level
2.
Population Normal
HGB level [g/dl]
Anemia
Mild Moderate Severe
Children 6-59 months of age ≥11.0 10-10.9 7.0-9.9 <7.0
Children 5-11 years of age ≥11.5 11-11.4 8.0-10.9 <8.0
Children 12-14 years of age ≥12.0 11-11.9 8.0-10.9 <8.0 Non-pregnant women (≥15 years of age) ≥12.0 11-11.9 8.0-10.9 <8.0
Pregnant women
a≥11.0 10-10.9 7.0-9.9 <7.0
Men (≥15 years of age) ≥13.0 11-12.9 8.0-10.9 <8.0
HGB, hemoglobin measured in grams per decilitre; a Because pregnancy changes blood pressure (BP) measures especially in the 2nd half, we excluded women who gave birth in the time frame of 7 weeks prior to the BP measurement or op to 20 weeks after (N=134). Since pregnancy at earlier stages is more difficult to determine, we did not identify early pregnancy status for exclusion or to apply the pregnancy-levels of anemia.
Supplementary Table 3 Blood pressure (BP) levels for (A) boys and (B) girls 5 to <18 years by age and height percentile and (C) those aged ≥18 years, in rural Gambia
(A) boys
a Age,y BP
Percentile SBP, mmHg DBP, mmHg
Percentile of Height Percentile of Height
5th 10th 25th 50th 75th 90th 95th 5th 10th 25th 50th 75th 90th 95th
5 50th 90 90 91 92 94 95 95 56 56 56 56 57 57 57
90th 101 102 103 104 106 107 107 67 67 67 67 68 68 68
95th 105 105 107 108 110 111 111 70 70 70 71 72 72 72
99th 112 113 114 116 118 119 120 78 78 78 78 79 79 79
6 50th 92 92 93 94 96 97 97 56 56 56 56 57 57 57
90th 104 104 105 107 108 109 110 67 67 67 68 68 68 68
95th 107 108 109 111 112 113 114 71 71 71 71 72 72 72
99th 115 116 117 119 120 122 122 79 78 79 79 80 80 80
7 50th 94 94 95 97 98 99 99 56 56 57 57 58 58 58
90th 106 106 108 109 110 112 112 68 68 68 68 69 69 69
95th 110 110 112 113 115 116 116 71 71 71 72 73 73 73
99th 118 118 120 121 123 124 125 79 79 79 80 81 81 81
8 50th 96 96 97 98 100 101 101 57 57 57 57 58 58 58
90th 108 108 110 111 112 114 114 68 68 68 69 69 69 69
95th 112 112 114 115 117 118 118 72 72 72 72 73 73 73
99th 120 121 122 123 125 126 127 80 80 80 80 81 81 81
9 50th 97 97 98 100 101 102 103 57 57 57 58 58 58 58
90th 109 110 111 112 114 115 116 69 69 69 69 70 70 70
95th 113 114 115 117 118 119 120 72 72 72 73 74 74 74
99th 122 122 124 125 127 128 129 80 80 80 81 82 82 82
10 50th 98 98 100 101 102 103 104 58 58 58 58 59 59 59
90th 111 111 112 114 115 116 117 69 69 69 70 71 71 70
95th 115 115 116 118 119 121 121 73 73 73 73 74 74 74
99th 123 124 125 126 128 130 130 81 81 81 82 83 83 82
11 50th 99 99 101 102 103 104 105 58 58 58 59 59 59 59
90th 112 112 113 115 116 118 118 70 70 70 70 71 71 71
95th 116 116 118 119 121 122 123 74 73 74 74 75 75 75
99th 124 125 126 128 129 131 131 82 82 82 82 83 83 83
12 50th 100 100 102 103 104 105 106 59 59 59 59 60 60 60
90th 113 113 115 116 117 119 119 70 70 70 71 72 72 72
95th 117 118 119 120 122 123 124 74 74 74 75 75 75 75
99th 126 126 127 129 131 132 133 82 82 82 83 84 84 84
13 50th 101 102 103 104 105 106 107 59 59 59 60 60 60 60
90th 114 115 116 117 119 120 120 71 71 71 71 72 72 72
95th 118 119 120 121 123 124 125 75 75 75 75 76 76 76
99th 127 127 129 130 132 133 134 83 83 83 83 84 84 84
14 50th 102 103 104 105 106 107 108 60 60 60 60 61 61 61
90th 115 116 117 118 120 121 122 71 71 71 72 73 73 73
95th 120 120 121 123 124 126 126 75 75 75 76 77 77 77
99th 128 129 130 132 134 135 136 83 83 83 84 85 85 85
15 50th 104 104 105 106 108 109 109 60 60 60 60 61 61 61
90th 117 118 119 120 122 123 123 72 72 72 72 73 73 73
95th 121 122 123 125 126 127 128 76 76 76 76 77 77 77
99th 130 131 132 134 135 137 137 84 84 84 85 86 86 86
16 50th 105 106 107 108 109 110 111 60 60 60 61 62 62 62
90th 119 119 121 122 123 125 125 72 72 72 73 74 74 74
95th 123 124 125 126 128 129 130 76 76 76 77 78 78 78
99th 132 133 134 136 137 139 139 85 85 85 85 86 86 86
17 50th 107 108 109 110 111 112 113 61 61 61 61 62 62 62
90th 121 121 123 124 125 127 127 73 73 73 73 74 74 74
95th 125 126 127 129 130 131 132 77 77 77 77 78 78 78
99th 135 135 136 138 140 141 142 85 85 85 86 87 87 87
(B) girls
a Age, yBP
Percentile
SBP, mmHg DBP, mmHg
Percentile of Height Percentile of Height
5th 10th 25th 50th 75th 90th 95th 5th 10th 25th 50th 75th 90th 95th
5 50th 95 95 95 95 96 97 98 58 58 58 58 58 59 59
90th 107 107 107 108 109 110 110 69 69 69 69 70 70 71
95th 111 111 111 112 113 114 114 73 73 73 73 74 74 75
99th 119 119 119 120 121 122 123 81 81 81 81 82 82 83
6 50th 96 96 96 97 98 99 99 59 59 59 59 59 59 60
90th 109 109 109 110 111 112 112 70 70 70 70 70 71 71
95th 113 113 113 114 115 116 116 74 74 74 74 74 75 75
99th 121 121 121 122 123 124 125 82 82 82 82 82 83 84
7 50th 98 98 98 98 99 100 101 59 59 59 59 59 60 60
90th 111 111 111 111 112 113 114 71 71 71 71 71 72 72
95th 115 115 115 115 116 118 118 75 75 75 75 75 76 76
99th 123 123 123 124 125 126 127 83 83 83 83 83 84 84
8 50th 99 100 100 100 101 102 102 60 60 60 60 60 60 61
90th 112 113 113 113 114 115 116 71 71 71 71 72 72 73
95th 117 117 117 117 118 119 120 75 75 75 75 76 76 77
99th 125 125 125 126 127 128 129 83 83 83 83 84 85 85
9 50th 101 101 101 102 102 103 104 60 60 60 60 60 61 61
90th 114 114 114 115 116 117 117 72 72 72 72 72 73 73
95th 118 118 119 119 120 121 122 76 76 76 76 76 77 77
99th 127 127 127 128 129 130 131 84 84 84 84 84 85 86
10 50th 102 102 103 103 104 105 105 60 60 60 60 61 61 62
90th 116 116 116 116 117 119 119 72 72 72 72 73 73 74
95th 120 120 120 121 122 123 123 76 76 76 76 77 77 78
99th 129 129 129 129 131 132 132 85 85 85 85 85 86 86
11 50th 104 104 104 104 105 106 107 61 61 61 61 61 62 62
90th 117 117 118 118 119 120 121 73 73 73 73 73 74 74
95th 122 122 122 122 123 124 125 77 77 77 77 77 78 78
99th 130 130 131 131 132 133 134 85 85 85 85 85 86 87
12 50th 105 105 105 106 107 107 108 61 61 61 61 61 62 62
90th 119 119 119 119 120 122 122 73 73 73 73 74 74 74
95th 123 123 123 124 125 126 127 77 77 77 77 78 78 79
99th 132 132 132 133 134 135 136 86 86 86 86 86 87 87
13 50th 106 106 106 107 108 109 109 62 62 62 62 62 62 63
90th 120 120 120 121 122 123 123 74 74 74 74 74 75 75
95th 125 125 125 125 126 127 128 78 78 78 78 78 79 79
14 50th 107 107 108 108 109 110 110 62 62 62 62 63 63 63
90th 121 121 122 122 123 124 125 75 75 75 75 75 75 76
95th 126 126 126 127 128 129 129 79 79 79 79 79 80 80
99th 135 135 135 136 137 138 139 87 87 87 87 88 88 89
15 50th 108 108 109 109 110 111 111 63 63 63 63 63 64 64
90th 123 123 123 123 124 125 126 75 75 75 75 76 76 77
95th 127 127 127 128 129 130 130 79 79 80 80 80 80 81
99th 136 136 136 137 138 139 140 88 88 88 88 89 89 90
16 50th 109 109 110 110 111 112 112 64 64 64 64 64 65 65
90th 124 124 124 124 125 126 127 77 77 77 77 77 77 78
95th 128 128 128 129 130 131 132 81 81 81 81 81 82 82
99th 137 138 138 138 139 140 141 90 90 90 90 90 91 91
17 50th 110 110 111 111 112 113 113 66 65 65 65 65 66 66
90th 125 125 125 126 127 128 128 78 78 78 78 78 79 79
95th 129 130 130 130 131 132 133 82 82 82 82 82 83 83
99th 139 139 139 139 141 142 142 91 91 91 91 91 92 93
(C) Adults
b Age,y Men and women
≥18 SBP ≥140 mmHg and/or ≥DBP>90
and/or receiving treatment for hypertension c
and/or being diagnosed as hypertensive in MRC Keneba clinical database
DBP, diastolic blood pressure; SBP, systolic blood pressure measured in millimetre of mercury (mmHg); y, years. a High-BP in <18y olds was defined as average of 2nd and 3rd SBP and/or diastolic BP (DBP) that is
≥95th percentile for sex, age, and height following the guidelines stipulated by the 4th Report 3 (Note: Our high-BP was determined applying population-specific age, sex and age-sex-specific height percentiles and is therefore directly comparable to the 4th Report hypertension definition, see main text for further detail). b Women who gave birth in the time frame of 7 weeks prior to the BP measurement or up to 20 weeks after, were excluded to avoid bias by pregnancy-induced hypertension. c Routinely prescribed anti-hypertensive drugs at the MRC Keneba clinic are Bendroflumethiazide, Atenolol, Propranolol, Captopril, Nifedipine and Methyldopa. Those receiving hypertension treatment from elsewhere excluded (N=24), since we had no means to verify the details of their prescription.
Supplementary Table 4 Age- and sex-specific height percentiles for girls and boys aged 5 to
<18y in rural Gambia
Age,y
Percentile of Height for boys, cm Percentile of Height for girls, cm
5th 10th 25th 50th 75th 90th 95th 5th 10th 25th 50th 75th 90th 95th 5 99 101 103 106 109 112 113 98 100 102 105 108 111 113 6 104 106 109 112 115 119 121 104 106 109 112 115 118 120 7 111 112 115 118 121 124 126 110 112 115 118 121 124 126 8 115 117 120 123 127 130 132 115 117 120 123 127 130 132 9 120 122 125 128 132 135 137 119 121 125 128 132 135 138 10 123 126 129 133 136 140 142 123 126 130 133 137 141 143 11 127 130 133 137 141 144 147 128 130 135 139 143 147 149 12 131 134 137 141 145 149 152 132 135 140 144 149 153 155 13 132 136 141 146 150 155 159 137 140 145 150 154 158 161 14 136 140 145 150 156 160 164 142 145 150 154 159 163 165 15 140 144 150 156 161 166 170 146 149 153 158 162 165 168 16 147 150 155 161 166 171 174 148 151 155 159 163 167 169 17 153 156 161 166 171 176 178 150 153 157 160 164 167 169 N=3637. For further details regarding the calculation of height percentiles please see statistical methods in main paper and above.
Supplementary Table 5 Blood pressure (BP) cut-offs for high-BP definition for (A) boys and (B) girls 5 to <18 years by age and height percentile in rural Gambians alongside cut-offs from the US 4
thReport
3(A) boys
a Age,y Source SBP cut-off (95th percentile), mmHg DBP cut-off (95th percentile), mmHg
Percentile of Height Percentile of Height
5th 10th 25th 50th 75th 90th 95th 5th 10th 25th 50th 75th 90th 95th
5 4th Report 108 109 110 112 114 115 116 69 70 71 72 73 74 74 Gambia 105 105 107 108 110 111 111 70 70 70 71 72 72 72 6 4th Report 109 110 112 114 115 117 117 72 72 73 74 75 76 76 Gambia 107 108 109 111 112 113 114 71 71 71 71 72 72 72 7 4th Report 110 111 113 115 117 118 119 74 74 75 76 77 78 78 Gambia 110 110 112 113 115 116 116 71 71 71 72 73 73 73 8 4th Report 111 112 114 116 118 119 120 75 76 77 78 79 79 80 Gambia 112 112 114 115 117 118 118 72 72 72 72 73 73 73 9 4th Report 113 114 116 118 119 121 121 76 77 78 79 80 81 81 Gambia 113 114 115 117 118 119 120 72 72 72 73 74 74 74 10 4th Report 115 116 117 119 121 122 123 77 78 79 80 81 81 82 Gambia 115 115 116 118 119 121 121 73 73 73 73 74 74 74 11 4th Report 117 118 119 121 123 124 125 78 78 79 80 81 82 82 Gambia 116 116 118 119 121 122 123 74 73 74 74 75 75 75 12 4th Report 119 120 122 123 125 127 127 78 79 80 81 82 82 83 Gambia 117 118 119 120 122 123 124 74 74 74 75 75 75 75 13 4th Report 121 122 124 126 128 129 130 79 79 80 81 82 83 83 Gambia 118 119 120 121 123 124 125 75 75 75 75 76 76 76 14 4th Report 124 125 127 128 130 132 132 80 80 81 82 83 84 84 Gambia 120 120 121 123 124 126 126 75 75 75 76 77 77 77 15 4th Report 126 127 129 131 133 134 135 81 81 82 83 84 85 85 Gambia 121 122 123 125 126 127 128 76 76 76 76 77 77 77 16 4th Report 129 130 132 134 135 137 137 82 83 83 84 85 86 87 Gambia 123 124 125 126 128 129 130 76 76 76 77 78 78 78 17 4th Report 131 132 134 136 138 139 140 84 85 86 87 87 88 89 Gambia 125 126 127 129 130 131 132 77 77 77 77 78 78 78
(B) girls
aAge,
y BP Percentile SBP cut-off (95th percentile), mmHg DBP cut-off (95th percentile), mmHg
Percentile of Height Percentile of Height
5th 10th 25th 50th 75th 90th 95th 5th 10th 25th 50th 75th 90th 95th
5 4th Report 107 107 108 110 111 112 113 70 71 71 72 73 73 74 Gambia 111 111 111 112 113 114 114 73 73 73 73 74 74 75 6 4th Report 108 109 110 111 113 114 115 72 72 73 74 74 75 76 Gambia 113 113 113 114 115 116 116 74 74 74 74 74 75 75 7 4th Report 110 111 112 113 115 116 116 73 74 74 75 76 76 77 Gambia 115 115 115 115 116 118 118 75 75 75 75 75 76 76 8 4th Report 112 112 114 115 116 118 118 75 75 75 76 77 78 78 Gambia 117 117 117 117 118 119 120 75 75 75 75 76 76 77 9 4th Report 114 114 115 117 118 119 120 76 76 76 77 78 79 79 Gambia 118 118 119 119 120 121 122 76 76 76 76 76 77 77
10 4th Report 116 116 117 119 120 121 122 77 77 77 78 79 80 80 Gambia 120 120 120 121 122 123 123 76 76 76 76 77 77 78 11 4th Report 118 118 119 121 122 123 124 78 78 78 79 80 81 81 Gambia 122 122 122 122 123 124 125 77 77 77 77 77 78 78 12 4th Report 119 120 121 123 124 125 126 79 79 79 80 81 82 82 Gambia 123 123 123 124 125 126 127 77 77 77 77 78 78 79 13 4th Report 121 122 123 124 126 127 128 80 80 80 81 82 83 83 Gambia 125 125 125 125 126 127 128 78 78 78 78 78 79 79 14 4th Report 123 123 125 126 127 129 129 81 81 81 82 83 84 84 Gambia 126 126 126 127 128 129 129 79 79 79 79 79 80 80 15 4th Report 124 125 126 127 129 130 131 82 82 82 83 84 85 85 Gambia 127 127 127 128 129 130 130 79 79 80 80 80 80 81 16 4th Report 125 126 127 128 130 131 132 82 82 83 84 85 85 86 Gambia 128 128 128 129 130 131 132 81 81 81 81 81 82 82 17 4th Report 125 126 127 129 130 131 132 82 83 83 84 85 85 86 Gambia 129 130 130 130 131 132 133 82 82 82 82 82 83 83 N=3637. For further details regarding the calculation of age- and sex-specific height and BP percentiles please see statistical methods in main paper and above. Note: Our high-BP and the hypertension categories as stipulated by the 4th Report are not directly comparable; we show these alongside each other for information purposes only.
Supplementary Table 6 Association between age and education status in ≥18y rural Gambian
Age group, n (%) Educated n=525 (%)
Non-educated n=1998 (%)
P
18-29 330 (48.6) 349 (51.4) <0.0001
30-39 128 (25.0) 384 (75.0)
40-49 55 (12.0) 404 (88.0)
50-59 8 (2.0) 392 (98.0)
60-69 2 (0.6) 311 (99.4)
70-79 1 (0.9) 116 (99.1)
>80 1 (2.3) 42 (97.7)
Information on education was available for those aged ≥18y; a participant was defined to be educated if s/he attended at least primary school. Row percentages are shown in educated and non-educated. The sum of the percentages in educated and non-educated within an age group is 100.