| Literature DB >> 24252691 |
Barbara A Forey1, John S Fry, Peter N Lee, Alison J Thornton, Katharine J Coombs.
Abstract
A higher concentration of high density lipoprotein cholesterol (HDL-C) in ex-smokers than smokers has consistently been observed. Better evidence of quitting effects comes from within-subject changes. We extend an earlier meta-analysis to quantify the reduction, and investigate variation by time quit and other factors. We conducted Medline and Cochrane searches for studies measuring HDL-C in subjects while still smoking and later having quit. Using unweighted and inverse-variance weighted regression analysis, we related changes (in mmol/l) to intra-measurement period, and estimated time quit, and to study type, location and start year, age, sex, product smoked, validation of quitting, baseline HDL-C, baseline and change in weight/BMI, and any study constraints on diet or exercise. Forty-five studies were identified (17 Europe, 16 North America, 11 Asia, 1 Australia). Thirteen were observational, giving changes over at least 12 months, with most involving >1000 subjects. Others were smoking cessation trials, 12 randomized and 20 non-randomized. These were often small (18 of <100 subjects) and short (14 of <10 weeks, the longest a year). Thirty studies provided results for only one time interval. From 94 estimates of HDL-C change, the unweighted mean was 0.107 (95% CI 0.085-0.128). The weighted mean 0.060 (0.044 to 0.075) was lower, due to smaller estimates in longer term studies. Weighted means varied by time quit (0.083, 0.112, 0.111, 0.072, 0.058 and 0.040 for <3, 3 to <6, 6 to <13, 13 to <27, 27 to <52 and 52+ weeks, p=0.006). After adjustment for time quit, estimates varied by study constraint on diet/exercise (p=0.003), being higher in studies requiring subjects to maintain their pre-quitting habits, but no other clear differences were seen, with significant (p<0.05) increases following quitting being evident in all subgroups studied, except where data were very limited. For both continuing and never smokers, the data are (except for two large studies atypically showing significant HDL-C declines in both groups, and a smaller decline in quitters) consistent with no change, and contrast markedly with the data for quitters. We conclude that quitting smoking increases HDL-C, and that this increase occurs rapidly after quitting, with no clear pattern of change thereafter.Entities:
Year: 2013 PMID: 24252691 PMCID: PMC4177613 DOI: 10.1186/2050-7771-1-26
Source DB: PubMed Journal: Biomark Res ISSN: 2050-7771
Literature searches
| PAPERS CITED BY PREVIOUS REVIEW [ | |
| Publications examined 27 | → Rejects (reason 1) 2 |
| ↓ | |
| Publications accepted (primary results) | |
| MEDLINE SEARCH 6TH July 2012 | |
| New abstracts examined 615 | → Rejects - total 500 |
| ↓ | Reason 1 – 442; Reason 3 – 40; Reason 5 – 7; Reason 6 – 1; Reason 7 – 7; Reason 8 – 3; |
| Publications examined 115c | → Rejects – total 91 |
| ↓ | Reason 1 – 80; Reason 3 – 2; Reason 5 – 1; Reason 6 – 1; Reason 7 – 5; Reason 8 – 2 |
| Publications accepted – total 24c | |
| Primary results | |
| Reviews 5 | |
| | |
| New abstracts examined 13 | → Rejects – total 7 |
| ↓ | Reason 1 – 5; Reason 8 – 2 |
| New publications examined 6d | → Rejects (reason 1) 6 |
| SECONDARY REFERENCES 15th August 2012e | |
| New abstracts examined 2 | → Rejects (reason 1) 1 |
| ↓ | |
| New publications examined 1 | → Rejects (reason 1) 1 |
| INFORMAL SEARCHING (including WBC review) | |
| New publications examined 4 | |
| ↓ | |
| New publications accepted – total 4 | |
| Primary results | |
| Reviews 1 | |
aReasons for rejection correspond to study inclusion/exclusion criteria (see Methods).
bIncludes one paper [11] where HDL-C data not used in the earlier review [4].
cIncludes one paper [12] initially rejected on the basis of the abstract but found to be relevant when examined for a separate review of WBC.
dOne paper could not be adequately identified, but another paper [13] by the same author and apparently reporting the same study was substituted.
eChecking continued until no new publications were identified.
Study details
| ALLEN | [ | USA | RCT | 6 weeks | 935 | B | 1990 |
| BASLER | [ | Germany | RCT | 3 months | 139 | B | 1990 |
| BURNET | [ | USA | Obs | 13 years | 417 | F | 1983-84 |
| ELIAS1 | [ | Sweden | Cess | 8 weeks | 40 | M | 1995 |
| ELIAS2 | [ | Sweden | Cess | 16 weeks | 58 | B | 1995-96 |
| FEHER | [ | UK | Cess | 2 weekse | 30 | B | 1988 |
| FERRAR | [ | USA | Cess | 4 weeks | 10 | F | 1999 |
| FORTMA | [ | USA | Obs/Int | 3 years | 40f | B | 1979-80 |
| GEPNER | [ | USA | RCT | 3 years | 923 | B | 2005-07 |
| GERACE | [ | USA | Obs/Int | 72 months | 3470 | M | 1973-76 |
| GREEN | [ | Israel | Obs | 1-4 years | 968 | M | 1985-87 |
| HAUSTE | [ | Germany | Cess | 6 months | 197 | M | 2001 |
| IINO | [ | Japan | Cess | 12 months | 41 | B | 2002-03 |
| KONDO | [ | Japan | Cess | 4 weeks | 29 | M | 2003 |
| KORHON | [ | USA | RCT | 15 weeks | 130 | F | 2004-07 |
| KUME | [ | Japan | Obs | 3 years | 3053 | B | 2003-07 |
| KUSHIM | [ | Japan | Obs | 5 years | 1431 | M | 1985 |
| LEE | [ | Korea | Cess | 2 months | 20 | M | 2009 |
| LUDVIK | [ | Iceland | RCT | 3 months | 157 | B | 1989 |
| MASARE | [ | Australia | Cess | 6 months | 64 | B | 1984 |
| MOFFA1 | [ | USA | Cess | 60 days | 36 | F | 1986 |
| MOFFA2 | [ | USA | Cess | 30 days | 45 | B | 1991 |
| MOFFA3 | [ | USA | RCT/Comm | 77 days | 43 | B | 1999 |
| NIAURA | [ | USA | RCT | 12 weeks | 28 | F | 1996 |
| NILSSO | [ | Sweden | RCT | 4 months | 400 | B | 1994 |
| NORREG | [ | Denmark | RCT | 1 year | 225 | B | 1994 |
| PRIEME | [ | Denmark | RCT | 26 weeks | 182 | B | 1996 |
| PULS | [ | Germany | Cess | 5 weeks | 218 | B | 2003-05 |
| QUENSE | [ | Sweden | Cess | 2 weeks | 24 | M | 1987 |
| RABKIN | [ | Canada | RCT | 2-3 months | 140 | B | 1982 |
| RAHILL | [ | USA | Obs | 30 years | 2280g | M | 1961-70 |
| RICHAR | [ | France | Cess | 3-12 weeks | 101 | B | 1995 |
| SHENNA | [ | UK | Obs | 4 years | 41f | M | 1980-83 |
| STAMFO | [ | USA | Cess | 48 days/1 year | 24 | F | 1984 |
| STUBBE | [ | Sweden | Cess | 6 weeks | 21 | M | 1981 |
| SUWAZO | [ | Japan | Obs | 15 years | 7058 | M | 1991-2002 |
| SWANK | [ | USA | Cess | 7 weeks | 19 | F | 1990 |
| TAMURA | [ | Japan | Obs/Int | 4 years | 1102 | M | 1999-2000 |
| TERRES | [ | Germany | Cess | 24 weeks | 121 | B | 1990-92 |
| TONSTA | [ | Norway | RCT | 1 year | 55 | B | 1999-2000 |
| VANDEN | [ | Netherlands | Cess | 1 year | 106 | M | 1997-98 |
| YAMAMO | [ | Japan | Obs | 3 years | 7321 | M | 1989 |
| YEH | [ | USA | Obs | 5 years | 10892 | B | 1987-89 |
| YOON | [ | Korea | Obs | 12 years | 2848 | M | 1995-2006 |
| ZHANG | [ | China | Cess | 3-6 months | 67 | M | 2009-10 |
aRCT = randomised controlled trial of a smoking cessation aid or method. RCT/Comm = RCT with community control group. Cess = other smoking cessation study. Obs/Int = observational study as follow-up to an intervention study (other than of smoking cessation). Obs = other observational study.
bTotal number of subjects in the study.
cB = both sexes, F = females, M = males.
dIf not stated the year before publication is assumed.
eSubjects were studied 2 weeks before and 2 weeks after stopping smoking.
fTotal number not stated, number shown is quitters FORTMA, SHENNA.
gOf the 2280 total participants, 1420 had at least 2 HDL-C measurements. An “observation” was taken as a successive pair of HDL-C measurements. Each person contributed between 1 and 9 (mean 4) observations to the total of 5895 observations analysed RAHILL.
hResults for a second study also reported by this paper were rejected as the subjects all had documented cardiovascular disease TONSTA.
Figure 1Change in HDL-C by time since quitting. The data are also shown in Additional file 2 (Table A2-1). Independent estimates for different times from study TAMURA are joined by a dashed line. Non-independent estimates for different times from other studies are joined by solid lines and distinguished by symbol and colour, as shown in the figure legend. Where there is a single estimate for a study/stratum, this is shown as a blue diamond: Week 2 FEHER-B, QUENSE-M, PULS-B. Week 4 FERRAR-F, KONDO-M, MOFFA1-F-R, NORREG-B, PRIEME-B-R. Week 5 RICHAR-B. Week 6 ALLEN-B, MASARE-M, MASARE-F. Week 7 STAMFO-F-R. Week 8 ELIAS2-B. Week 9 BASLER-B, LEE-M, NIAURA-F-E, NIAURA-F-C. Week 10 RABKIN-M, RABKIN-F. Week 12, KORHON-F, TONSTA-B. Week 13 LUDVIK-B. Week 19 ZHANG-M. Week 23 TERRES-B. Week 44 YOON-M-L, YOON-M-H. Week 52 GEPNER-B. Week 65 GREEN-M. Week 78, FORTMA-B, RAHILL-M, YEH-B. Week 119 SHENNA-M. Week 130 KUSHIM-M. Week 156 GERACE-M. Note that each individual independent point and the start of each group of non-independent points effectively joins back to the (0,0) point, but this is not shown in the Figure for clarity. Note also that the scale on the x-axis is non-linear (with distances between 13 and 52 weeks reduced to a quarter, and over 52 weeks to a tenth). Abbreviations: B = both sexes, F = females, M = males; L=low weight gain (<1.3 kg), H=high weight gain (≥1.3 kg); P = persistent quitter, R = resumed smoking before end of study; E = exercise training intervention, C = control group.
Estimates of change in total HDL-C (mmol/l) following quitting
| Overall | | 94 | 0.107 (0.085 to 0.128) | <0.001 | 0.060 (0.044 to 0.075) | <0.001 |
| | | | | | | |
| Periodd | <3 weeks | 21 | 0.102 (0.047 to 0.157) | 0.04 | 0.100 (0.032 to 0.169) | <0.001 |
| | 3 to <6 | 21 | 0.102 (0.063 to 0.141) | | 0.082 (0.042 to 0.123) | |
| | 6 to <13 | 20 | 0.157 (0.119 to 0.194) | | 0.131 (0.094 to 0.168) | |
| | 13 to <27 | 11 | 0.107 (0.057 to 0.158) | | 0.108 (0.061 to 0.155) | |
| | 27 to <52 | 1 | 0.100 (−0.068 to 0.268) | | 0.094 (−0.221 to 0.409) | |
| | 52+ weeks | 20 | 0.065 (0.027 to 0.102) | | 0.041 (0.026 to 0.057) | |
| Time quite | <3 weeks | 23 | 0.101 (0.050 to 0.152) | NS | 0.083 (0.030 to 0.137) | 0.006 |
| | 3 to <6 | 20 | 0.115 (0.075 to 0.155) | | 0.112 (0.069 to 0.154) | |
| | 6 to <13 | 22 | 0.145 (0.109 to 0.181) | | 0.111 (0.075 to 0.148) | |
| | 13 to <27 | 9 | 0.099 (0.042 to 0.156) | | 0.072 (0.036 to 0.109) | |
| | 27 to <52 | 4 | 0.088 (0.003 to 0.173) | | 0.058 (−0.004 to 0.121) | |
| | 52+ weeks | 16 | 0.062 (0.020 to 0.105) | | 0.040 (0.023 to 0.057) | |
| | | | | | | |
| Max Agef | <50 years | 8 | 0.124 (0.047 to 0.201) | NS | 0.161 (0.072 to 0.250) | NS |
| | 50-70 years | 28 | 0.107 (0.071 to 0.144) | | 0.065 (0.038 to 0.093) | |
| | >70 years | 58 | 0.094 (0.063 to 0.125) | | 0.080 (0.057 to 0.104) | |
| Sex | Male | 46 | 0.090 (0.060 to 0.121) | NS | 0.073 (0.046 to 0.099) | NS |
| | Female | 30 | 0.139 (0.094 to 0.184) | | 0.123 (0.061 to 0.186) | |
| | Combined | 18 | 0.095 (0.052 to 0.138) | | 0.078 (0.050 to 0.107) | |
| Continent | N America | 49 | 0.121 (0.082 to 0.160) | NS | 0.055 (0.024 to 0.087) | NS |
| | Europe | 30 | 0.110 (0.075 to 0.146) | | 0.096 (0.062 to 0.130) | |
| | Asia | 13 | 0.067 (0.016 to 0.118) | | 0.081 (0.050 to 0.112) | |
| | Australia | 2 | 0.026 (−0.099 to 0.152) | | 0.018 (−0.179 to 0.215) | |
| Timingg | <1990 | 26 | 0.119 (0.077 to 0.160) | NS | 0.049 (0.016 to 0.082) | 0.08 |
| | 1990-1999 | 58 | 0.100 (0.071 to 0.129) | | 0.088 (0.065 to 0.110) | |
| | 2000+ | 10 | 0.071 (0.012 to 0.130) | | 0.077 (0.040 to 0.114) | |
| Study type | Observational | 16 | 0.094 (0.031 to 0.157) | NS | 0.086 (0.057 to 0.115) | NS |
| | RCT | 16 | 0.093 (0.042 to 0.145) | | 0.090 (0.057 to 0.123) | |
| | Other | 62 | 0.108 (0.073 to 0.143) | | 0.067 (0.040 to 0.093) | |
| Product smoked | Any | 16 | 0.102 (0.056 to 0.148) | NS | 0.103 (0.072 to 0.133) | 0.09 |
| | Cigarettes | 67 | 0.102 (0.075 to 0.130) | | 0.069 (0.047 to 0.091) | |
| | Cigarettes only | 11 | 0.095 (0.035 to 0.155) | | 0.092 (0.054 to 0.129) | |
| Validation of quitting | Yes | 48 | 0.113 (0.077 to 0.149) | NS | 0.088 (0.060 to 0.115) | NS |
| | No | 46 | 0.092 (0.059 to 0.125) | | 0.075 (0.051 to 0.098) | |
| Constraint on diet/exercise | Stay same | 15 | 0.141 (0.089 to 0.193) | 0.09 | 0.191 (0.126 to 0.255) | 0.003 |
| | Improve | 9 | 0.135 (0.076 to 0.193) | | 0.064 (0.036 to 0.092) | |
| | No constraint | 70 | 0.087 (0.061 to 0.114) | | 0.082 (0.066 to 0.099) | |
| Baseline HDL-C | 1st tertile | 34 | 0.111 (0.070 to 0.151) | NS | 0.101 (0.068 to 0.134) | 0.03 |
| | 2nd tertile | 25 | 0.131 (0.083 to 0.178) | | 0.097 (0.048 to 0.147) | |
| | 3rd tertile | 28 | 0.100 (0.064 to 0.135) | | 0.084 (0.061 to 0.108) | |
| | unknown | 7 | 0.044 (−0.030 to 0.118) | | 0.042 (0.010 to 0.073) | |
| Baseline weight/BMIh | 1st tertile | 19 | 0.132 (0.066 to 0.199) | NS | 0.154 (0.042 to 0.267) | NS |
| | 2nd tertile | 28 | 0.073 (0.039 to 0.108) | | 0.073 (0.048 to 0.098) | |
| | 3rd tertile | 21 | 0.111 (0.060 to 0.163) | | 0.112 (0.065 to 0.158) | |
| | unknown | 26 | 0.120 (0.083 to 0.156) | | 0.076 (0.047 to 0.105) | |
| Change in weight/BMIh | 1st tertile | 5 | 0.155 (0.077 to 0.232) | NS | 0.161 (0.092 to 0.230) | 0.06 |
| | 2nd tertile | 29 | 0.076 (0.031 to 0.121) | | 0.074 (0.022 to 0.125) | |
| | 3rd tertile | 51 | 0.100 (0.073 to 0.128) | | 0.065 (0.041 to 0.089) | |
| | unknown | 9 | 0.105 (0.041 to 0.170) | | 0.104 (0.042 to 0.166) | |
| Baseline LDL-C | 1st tertile | 17 | 0.067 (0.001 to 0.132) | NS | 0.092 (0.045 to 0.139) | NS |
| | 2nd tertile | 16 | 0.132 (0.063 to 0.201) | | 0.084 (0.017 to 0.150) | |
| | 3rd tertile | 17 | 0.085 (0.039 to 0.130) | | 0.071 (0.028 to 0.113) | |
| | unknown | 44 | 0.110 (0.079 to 0.141) | | 0.080 (0.054 to 0.106) | |
| Baseline Triglycerides | 1st tertile | 26 | 0.134 (0.085 to 0.184) | NS | 0.099 (0.017 to 0.181) | NS |
| | 2nd tertile | 13 | 0.108 (0.059 to 0.157) | | 0.099 (0.034 to 0.163) | |
| | 3rd tertile | 24 | 0.075 (0.027 to 0.123) | | 0.079 (0.044 to 0.114) | |
| | unknown | 31 | 0.096 (0.062 to 0.130) | | 0.075 (0.050 to 0.099) | |
| Baseline Systolic BP | 1st tertile | 8 | 0.079 (0.015 to 0.142) | NS | 0.060 (0.006 to 0.115) | NS |
| | 2nd tertile | 7 | 0.117 (0.046 to 0.188) | | 0.096 (0.058 to 0.134) | |
| | 3rd tertile | 5 | 0.066 (−0.016 to 0.148) | | 0.090 (0.056 to 0.125) | |
| | unknown | 74 | 0.107 (0.079 to 0.135) | | 0.075 (0.052 to 0.098) | |
| Baseline Diastolic BP | 1st tertile | 8 | 0.079 (0.015 to 0.142) | NS | 0.060 (0.006 to 0.115) | NS |
| | 2nd tertile | 7 | 0.117 (0.046 to 0.188) | | 0.096 (0.058 to 0.134) | |
| | 3rd tertile | 5 | 0.066 (−0.016 to 0.148) | | 0.090 (0.056 to 0.125) | |
| unknown | 74 | 0.107 (0.079 to 0.135) | 0.075 (0.052 to 0.098) | |||
aSee Additional file 2 (Table A2-1) for data used on change and SE. Analyses are based on repeated measures analysis of variance using the Kenward-Roger method.
bNumber of estimates that the mean is based on.
cNS p≥0.1. For the overall analysis, this is based on a test for an increase following quitting. For the subgroup analysis, this tests for variation by subgroup level.
dPeriod between first measurement when smoking and second measurement when not smoking (using mean, median or midpoint where necessary).
eBest estimate of time since quit at second measurement.
fMaximum age of population at baseline.
gBased on year of start of study.
hUsing data for weight if both weight and BMI available (see Methods).
Effects of adjustment on change in HDL-C (mmol/l) following quitting
| GERACEd | M | 313 (156) | none | 0.021 | age, baseline HDL-C, serum thiocyanate, weight change, Hegsted score change, medications, alcohol, DBP | 0.062 |
| GREENe | M | 52-209 av 130 (65) | age | 0.044 | + change in BMI, alcohol, coffee, sport | 0.044 |
| KUSHIM | M | 261 (130.5) | none | −0.138 | change in BMI | −0.092 |
| PRIEMEd | B | 4 | none | 0.122 | baseline HDL-C | 0.120 |
| RAHILLd | M | 156 (78)f | age | 0.026 | + baseline HDL-C, LDL-C, diabetes, hypertension, CVD, CHD, medications | 0.041 |
| STUBBE | M | 2 | none | 0.238 | change in dietary fat | 0.179 |
| SUWAZOg | M | 52 (26) | age, day/shift work, alcohol, exercise | 0.044 | + change in BMI | 0.067 |
| | | 104 (78) | | 0.065 | | 0.100 |
| | | 156 (130) | | 0.072 | | 0.098 |
| YOON | Mg | 52-156 av 88 (44) | None | 0.045 | age, amount smoked, time between measurements, education, economic status, marital status, diabetes, hypertension, alcohol, inactivity | 0.045 |
| | M-Lh | | | 0.051 | | 0.047 |
| M-Hh | 0.039 | 0.031 | ||||
aData are shown for estimates of change in HDL-C which are equivalent except for the level of adjustment.
bB = both sexes, F = females, M = males; L=low weight gain (<1.3 kg), H=high weight gain (≥1.3 kg).
cPeriod (weeks) between first measurement when smoking and second measurement when quitting. The estimated time quit is shown in parentheses, if different. “av” = average.
dChange is relative to continuing smokers (change in quitters minus change in continuing smokers) GERACE, PRIEME, RAHILL.
eChange is relative to never smokers (change in quitters minus change in never smokers) GREEN.
fResults are adjusted to 3 year interval RAHILL.
gAdjusted change estimated from a two-group analysis (quitters and continuing smokers) SUWAZO, YOON.
hAdjusted change estimated from a two-group analysis (low and high weight gain) YOON.