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Ahmad, Shafqat
Publications (6 of 6) Show all publications
Warensjö Lemming, E., Byberg, L., Stattin, K., Ahmad, S., Lind, L., Elmsfahl, S., . . . Michaëlsson, K. (2019). Dietary Pattern Specific Protein Biomarkers for Cardiovascular Disease: A Cross-Sectional Study in 2 Independent Cohorts. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 8(11), Article ID e011860.
Open this publication in new window or tab >>Dietary Pattern Specific Protein Biomarkers for Cardiovascular Disease: A Cross-Sectional Study in 2 Independent Cohorts
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2019 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 8, no 11, article id e011860Article in journal (Refereed) Published
Abstract [en]

Background: Mechanisms related to the influence of diet on the development of cardiovascular disease are not entirely understood, and protein biomarkers may help to understand these pathways. Studies of biomarkers identified with multiplex proteomic methods and dietary patterns are largely lacking.

Methods and Results: Dietary patterns were generated through principal component analysis in 2 population‐based Swedish cohorts, the EpiHealth (EpiHealth study; n=20 817 men and women) and the SMCC (Swedish Mammography Cohort Clinical [n=4650 women]). A set of 184 protein cardiovascular disease biomarkers were measured with 2 high‐throughput, multiplex immunoassays. Discovery and replication multivariable linear regression analyses were used to investigate the associations between the principal component analysis–generated dietary patterns and the cardiovascular disease–associated protein biomarkers, first in the EpiHealth (n=2240) and then in the Swedish Mammography Cohort Clinical. Four main dietary patterns were identified in the EpiHealth, and 3 patterns were identified in the Swedish Mammography Cohort Clinical. The healthy and the Western/traditional patterns were found in both cohorts. In the EpiHealth, 57 protein biomarkers were associated with 3 of the dietary patterns, and 41 of these associations were replicated in the Swedish Mammography Cohort Clinical, with effect estimates ranging from 0.057 to 0.083 (P‐value range, 5.0×10−2–1.4×10−9) for each SD increase in the relative protein concentration. Independent associations were established between dietary patterns and the 21 protein biomarkers. Two proteins, myeloperoxidase and resistin, were associated with both the healthy and the light meal pattern but in opposite directions.

Conclusions: We have discovered and replicated independent associations between dietary patterns and 21 biomarkers linked to cardiovascular disease, which have a role in the pathways related to inflammation, endothelial and immune function, cell adhesion, and metabolism

Keywords
cardiovascular disease, dietary patterns, EpiHealth study, inflammation, proteomics, Swedish Mammography Cohort Clinical
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:uu:diva-394981 (URN)10.1161/JAHA.118.011860 (DOI)000484576200019 ()31433701 (PubMedID)
Funder
Swedish Research Council, 2017-06100Swedish Research Council, 2015-05997Swedish Research Council, 2015-03257Forte, Swedish Research Council for Health, Working Life and Welfare, 2017-00721Swedish Research Council, 2017/49 (180)
Available from: 2019-10-11 Created: 2019-10-11 Last updated: 2019-10-11Bibliographically approved
Ahmad, S. & Ahluwalia, T. S. (2019). Editorial: The Role of Genetic and Lifestyle Factors in Metabolic Diseases. Frontiers in Endocrinology, 10, Article ID 475.
Open this publication in new window or tab >>Editorial: The Role of Genetic and Lifestyle Factors in Metabolic Diseases
2019 (English)In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 10, article id 475Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
Frontiers Media S.A., 2019
Keywords
gene environment interaction, obesity, type 2 diabetes, cardiovascular disease, genetic predisposition and association
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-390424 (URN)10.3389/fendo.2019.00475 (DOI)000475890100001 ()31379743 (PubMedID)
Funder
Swedish Heart Lung Foundation, 20170988Novo Nordisk, NNF18OC0052457
Available from: 2019-08-12 Created: 2019-08-12 Last updated: 2019-08-12Bibliographically approved
Ahmad, S., Fatima, S. S., Rukh, G. & Smith, C. E. (2019). Gene Lifestyle Interactions With Relation to Obesity, Cardiometabolic, and Cardiovascular Traits Among South Asians. Frontiers in Endocrinology, 10, Article ID 221.
Open this publication in new window or tab >>Gene Lifestyle Interactions With Relation to Obesity, Cardiometabolic, and Cardiovascular Traits Among South Asians
2019 (English)In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 10, article id 221Article, review/survey (Refereed) Published
Abstract [en]

The rapid rise of obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) during the last few decades among South Asians has been largely attributed to a major shift in lifestyles including physical inactivity, unhealthy dietary patterns, and an overall pattern of sedentary lifestyle. Genetic predisposition to these cardiometabolic risk factors may have interacted with these obesogenic environments in determining the higher cardiometabolic disease prevalence. Based on the premise that gene-environment interactions cause obesity and cardiometabolic diseases, we systematically searched the literature and considered the knowledge gaps that future studies might ful fill. We identified only seven published studies that focused specifically on gene-environment interactions for cardiometabolic traits in South Asians, most of which were limited by relatively small sample and lack of replication. Some studies reported that the differences in metabolic response to higher physical activity and low caloric diet might be modified by genetic risk related to these cardiometabolic traits. Although studies on gene lifestyle interactions in cardiometabolic traits report significant interactions, future studies must focus on more precise assessment of lifestyle factors, investigation of a larger set of genetic variants and the application of powerful statistical methods to facilitate translatable approaches. Future studies should also be integrated with findings both using mechanistic studies through laboratory settings and randomized clinical trials for clinical outcomes.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2019
Keywords
gene environment interaction, South Asians, obesity, cardiometabolic traits, cardiovasclar disease
National Category
Medical Genetics Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-382765 (URN)10.3389/fendo.2019.00221 (DOI)000463927500001 ()31024458 (PubMedID)
Funder
Swedish Heart Lung Foundation, 20150711Swedish Heart Lung Foundation, 20170988
Available from: 2019-05-03 Created: 2019-05-03 Last updated: 2019-05-03Bibliographically approved
Ahmad, S., Mora, S., Ridker, P. M., Hu, F. B. & Chasman, D. I. (2019). Gene-Based Elevated Triglycerides and Type 2 Diabetes Mellitus Risk in the Women's Genome Health Study. Arteriosclerosis, Thrombosis and Vascular Biology, 39(1), 97-106
Open this publication in new window or tab >>Gene-Based Elevated Triglycerides and Type 2 Diabetes Mellitus Risk in the Women's Genome Health Study
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2019 (English)In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 39, no 1, p. 97-106Article in journal (Refereed) Published
Abstract [en]

Objective- Higher triglyceride (TG) is a risk factor for incident type 2 diabetes mellitus (T2DM), but paradoxically, genetic susceptibility for higher TG has been associated with lower T2DM risk. There is also evidence that the genetic association may be modified by baseline TG. Whether such associations can be replicated and the interaction is selective for certain TG-rich lipoprotein particles remains to be explored.

Approach and Results-Cox regression involving TG, TG-rich lipoprotein particles, and genetic determinants of TG was performed among 15 813 participants with baseline fasting status in the WGHS (Women's Genome Health Study), including 1453 T2DM incident cases during a mean 18.6 (SD= 5.3) years of follow-up. A weighted, 40-single-nucleotide polymorphism TG genetic risk score was inversely associated with incident T2DM (hazard ratio [95% CI], 0.66 [0.580.75]/ 10-TG risk alleles; P< 0.0001) with adjustment for baseline body mass index, HDL (high-density lipoprotein) cholesterol, and TG. TG-associated risk was higher among individuals in the low compared with the high 40-singlenucleotide polymorphism TG genetic risk score tertile (hazard ratio [95% CI], 1.98 [1.83-2.14] versus 1.68 [1.58-1.80] per mmol/L; P-interaction = 0.0007). In TG-adjusted analysis, large and medium but not small TG-rich lipoprotein particles were associated with higher T2DM incidence for successively lower 40-single-nucleotide polymorphism TG genetic risk score tertiles, P-interaction = 0.013, 0.012, and 0.620 across tertiles, respectively.

Conclusions-Our results confirm the previous observations of the paradoxical associations of TG with T2DM while focusing attention on the larger TG-rich lipoprotein particle subfractions, suggesting their importance in clinical profiling of T2DM risk.

Keywords
diabetes mellitus, type 2, genetic predisposition, lipid metabolism, lipoproteins, VLDL, triglycerides
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-398546 (URN)10.1161/ATVBAHA.118.311562 (DOI)000454313300015 ()30565958 (PubMedID)
Funder
Swedish Heart Lung Foundation, 20150711
Available from: 2019-12-10 Created: 2019-12-10 Last updated: 2019-12-10Bibliographically approved
Marouli, E., Del Greco, M. F., Astley, C. M., Yang, J., Ahmad, S., Berndt, S. I., . . . Deloukas, P. (2019). Mendelian randomisation analyses find pulmonary factors mediate the effect of height on coronary artery disease. COMMUNICATIONS BIOLOGY, 2, Article ID 119.
Open this publication in new window or tab >>Mendelian randomisation analyses find pulmonary factors mediate the effect of height on coronary artery disease
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2019 (English)In: COMMUNICATIONS BIOLOGY, ISSN 2399-3642, Vol. 2, article id 119Article in journal (Refereed) Published
Abstract [en]

There is evidence that lower height is associated with a higher risk of coronary artery disease (CAD) and increased risk of type 2 diabetes (T2D). It is not clear though whether these associations are causal, direct or mediated by other factors. Here we show that one standard deviation higher genetically determined height (similar to 6.5 cm) is causally associated with a 16% decrease in CAD risk (OR = 0.84, 95% CI 0.80-0.87). This causal association remains after performing sensitivity analyses relaxing pleiotropy assumptions. The causal effect of height on CAD risk is reduced by 1-3% after adjustment for potential mediators (lipids, blood pressure, glycaemic traits, body mass index, socio-economic status). In contrast, our data suggest that lung function (measured by forced expiratory volume [FEV1] and forced vital capacity [FVC]) is a mediator of the effect of height on CAD. We observe no direct causal effect of height on the risk of T2D.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-382527 (URN)10.1038/s42003-019-0361-2 (DOI)000463365700001 ()30937401 (PubMedID)
Available from: 2019-04-26 Created: 2019-04-26 Last updated: 2019-04-26Bibliographically approved
Ahmad, S., Moorthy, M. V., Demler, O. V., Hu, F. B., Ridker, P. M., Chasman, D. I. & Mora, S. (2018). Assessment of Risk Factors and Biomarkers Associated With Risk of Cardiovascular Disease Among Women Consuming a Mediterranean Diet. JAMA NETWORK OPEN, 1(8), Article ID e185708.
Open this publication in new window or tab >>Assessment of Risk Factors and Biomarkers Associated With Risk of Cardiovascular Disease Among Women Consuming a Mediterranean Diet
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2018 (English)In: JAMA NETWORK OPEN, ISSN 2574-3805, Vol. 1, no 8, article id e185708Article in journal (Refereed) Published
Abstract [en]

IMPORTANCE Higher Mediterranean diet (MED) intake has been associated with lower risk of cardiovascular disease (CVD), but limited data are available about the underlying molecular mechanisms of this inverse disease association in human populations.

OBJECTIVE To better characterize the relative contribution of traditional and novel factors to the MED-related risk reduction in CVD events in a US population.

DESIGN, SETTING, AND PARTICIPANTS Using a prospective cohort design, baseline MED intake was assessed in 25 994 initially healthy US women in theWomen's Health Study who were followed up to 12 years. Potential mediating effects of a panel of 40 biomarkers were evaluated, including lipids, lipoproteins, apolipoproteins, inflammation, glucose metabolism and insulin resistance, branched-chain amino acids, small-molecule metabolites, and clinical factors. Baseline study information and samples were collected between April 30, 1993, and January 24, 1996. Analyses were conducted between August 1, 2017, and October 30, 2018.

EXPOSURES Intake of MED is a 9-category measure of adherence to a Mediterranean dietary pattern. Participants were categorized into 3 levels based on their adherence to the MED.

MAIN OUTCOMES AND MEASURES Incident CVD confirmed through medical records and the proportion of CVD risk reduction explained by mediators.

RESULTS Among 25 994women (mean [SD] age, 54.7 [7.1] years), those with low, middle, and upper MED intakes composed 39.0%, 36.2%, and 24.8% of the study population and experienced 428 (4.2%), 356 (3.8%), and 246 (3.8%) incident CVD events, respectively. Compared with the reference group who had low MED intake, CVD risk reductions were observed for the middle and upper groups, with respective HRs of 0.77 (95% CI, 0.67-0.90) and 0.72 (95% CI, 0.61-0.86) (P for trend < .001). The largest mediators of the CVD risk reduction of MED intake were biomarkers of inflammation (accounting for 29.2% of the MED-CVD association), glucose metabolism and insulin resistance (27.9%), and body mass index (27.3%), followed by blood pressure (26.6%), traditional lipids (26.0%), high-density lipoprotein measures (24.0%) or very low-density lipoprotein measures (20.8%), with lesser contributions from low-density lipoproteins (13.0%), branched-chain amino acids (13.6%), apolipoproteins (6.5%), or other small-molecule metabolites (5.8%).

CONCLUSIONS AND RELEVANCE In this study, higher MED intake was associated with approximately one-fourth relative risk reduction in CVD events, which could be explained in part by known risk factors, both traditional and novel.

Place, publisher, year, edition, pages
AMER MEDICAL ASSOC, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-376897 (URN)10.1001/jamanetworkopen.2018.5708 (DOI)000456295400002 ()30646282 (PubMedID)
Funder
Swedish Heart Lung Foundation, 20150711Swedish Heart Lung Foundation, 20170988
Available from: 2019-02-13 Created: 2019-02-13 Last updated: 2019-02-13Bibliographically approved
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